Guidance for Practicing Primary Care

The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

• Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
• In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
• For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

• Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
• If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
• If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.

Diabetes mellitus in adults:

• In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
• In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
• In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
• In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

• Individualized risk and treatment discussion should be done with clinician and patient.
• Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
• Risk-enhancing factors can favor initiation of intensification of statin therapy.
• If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

• Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
• In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
• For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

• Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
• If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
• If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.

Diabetes mellitus in adults:

• In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
• In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
• In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
• In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

• Individualized risk and treatment discussion should be done with clinician and patient.
• Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
• Risk-enhancing factors can favor initiation of intensification of statin therapy.
• If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

The purpose of this guideline is to provide direction for the management of patients with high blood cholesterol to decrease the incidence of atherosclerotic vascular disease. The update was undertaken because new evidence has emerged since the publication of the 2013 ACC/AHA cholesterol guideline about additional cholesterol-lowering agents including ezetimibe and PCSK9 inhibitors.

Measurement and therapeutic modalities

In adults aged 20 years and older who are not on lipid-lowering therapy, measurement of a lipid profile is recommended and is an effective way to estimate atherosclerotic cardiovascular disease (ASCVD) risk and documenting baseline LDL-C.

Statin therapy is divided into three categories: High-intensity statin therapy aims for lowering LDL-C levels by more than 50%, moderate-intensity therapy by 30%-49%, and low-intensity therapy by less than 30%.
 

Cholesterol management groups

In all individuals at all ages, emphasizing a heart-healthy lifestyle, meaning appropriate diet and exercise, to decrease the risk of developing ASCVD should be advised.

Individuals fall into groups with distinct risk of ASCVD or recurrence of ASCVD and the recommendations are organized according to these risk groups.

Secondary ASCVD prevention: Patients who already have ASCVD by virtue of having had an event or established diagnosis (MI, angina, cerebrovascular accident, or peripheral vascular disease) fall into the secondary prevention category:

• Patients aged 75 years and younger with clinical ASCVD: High-intensity statin therapy should be initiated with aim to reduce LDL-C levels by 50%. In patients who experience statin-related side effects, a moderate-intensity statin should be initiated with the aim to reduce LDL-C by 30%-49%.
• In very high-risk patients with an LDL-C above 70 mg/dL on maximally tolerated statin therapy, it is reasonable to consider the use of a non–statin cholesterol-lowering agent with an LDL-C goal under 70 mg/dL. Ezetimibe (Zetia) can be used initially and if LDL-C remains above 70 mg/dL, then consideration can be given to the addition of a PCSK9-inhibitor therapy (strength of recommendation: ezetimibe – moderate; PCSK9 – strong). The guideline discusses that, even though the evidence supports the efficacy of PCSK9s in reducing the incidence of ASCVD events, the expense of PCSK9 inhibitors give them a high cost, compared with value.
• For patients more than age 75 years with established ASCVD, it is reasonable to continue high-intensity statin therapy if patient is tolerating treatment.

Severe hypercholesterolemia:

• Patients with LDL-C above 190 mg/dL do not need a 10-year risk score calculated. These individuals should receive maximally tolerated statin therapy.
• If patient is unable to achieve 50% reduction in LDL-C and/or have an LDL-C level of 100 mg/dL, the addition of ezetimibe therapy is reasonable.
• If LDL-C is still greater than 100mg/dL on a statin plus ezetimibe, the addition of a PCSK9 inhibitor may be considered. It should be recognized that the addition of a PCSK9 in this circumstance is classified as a weak recommendation.

Diabetes mellitus in adults:

• In patients aged 40-75 years with diabetes, regardless of 10-year ASCVD risk, should be prescribed a moderate-intensity statin (strong recommendation).
• In adults with diabetes mellitus and multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with goal to reduce LDL-C by more than 50%.
• In adults with diabetes mellitus and 10-year ASCVD risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce LDL-C levels by 50% or more.
• In patients aged 20-39 years with diabetes that is either of long duration (at least 10 years, type 2 diabetes mellitus; at least 20 years, type 1 diabetes mellitus), or with end-organ damage including albuminuria, chronic renal insufficiency, retinopathy, neuropathy, or ankle-brachial index below 0.9, it may be reasonable to initiate statin therapy (weak recommendation).

Primary prevention in adults: Adults with LDL 70-189 mg/dL and a 10-year risk of a first ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the pooled cohort equation. Adults should be categorized according to calculated risk of developing ASCVD: low risk (less than 5%), borderline risk (5% to less than 7.5%), intermediate risk (7.5% and higher to less than 20%), and high risk (20% and higher) (strong recommendation:

• Individualized risk and treatment discussion should be done with clinician and patient.
• Adults in the intermediate-risk group (7.5% and higher to less than 20%), should be placed on moderate-intensity statin with LDL-C goal reduction of more than 30%; for optimal risk reduction, especially in high-risk patients, an LDL-C reduction of more than 50% (strong recommendation).
• Risk-enhancing factors can favor initiation of intensification of statin therapy.
• If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. If CAC is zero, statin therapy may be withheld or delayed, except those with diabetes as above, smokers, and strong familial hypercholesterolemia with premature ASCVD. If CAC score is 1-99, it is reasonable to initiate statin therapy for patients older than age 55 years; If CAC score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate a statin.

Statin safety: Prior to initiation of a statin, a clinician-patient discussion is recommended detailing ASCVD risk reduction and the potential for side effects/drug interactions. In patients with statin-associated muscle symptoms (SAMS), a detailed account for secondary causes is recommended. In patients with true SAMS, it is recommended to check a creatine kinase level and hepatic function panel; however, routine measurements are not useful. In patients with statin-associated side effects that are not severe, reassess and rechallenge patient to achieve maximal lowering of LDL-C with a modified dosing regimen.
 

The bottom line

Lifestyle modification is important at all ages, with specific population-guided strategies for lowering cholesterol in subgroups as discussed above. Major changes to the AHA/ACC Cholesterol Clinical Practice Guidelines now mention new agents for lowering cholesterol and using CAC levels as predictability scoring.

Reference

Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Palko is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

Importance

While statins remain the foundation for treating high cholesterol in order to reduce cardiovascular risk, new evidence has lead to important revisions in the American Heart Association’s recommendations for treatment of hypercholesterolemia in patients at very high cardiovascular risk (secondary prevention) with the addition of specific nonstatin agents. We will briefly review the AHA 2013 guideline recommendations, the relevant new information, and the updated AHA recommendations.

American Heart Association 2013 guidelines

The 2013 American College of Cardiology/AHA cholesterol guidelines recommend either high- or moderate-intensity statin therapy for patients in the four statin benefit groups:

1. Adult patients older than 21 years of age with clinical atherosclerotic cardiovascular disease (ASCVD).

2. Adults older than 21 years of age with low-density lipoprotein cholesterol (LDL-C) above 190 mg/dL.

3. Adults aged 40-75 years without ASCVD but with diabetes and with LDL-C 70-189 mg/dL.

4. Adults aged 40-75 years without either ASCVD or diabetes, with LDL-C 70-189 mg/dL and an estimated 10-year risk for ASCVD of over 7.5% as determined by the Pooled Cohort Equations.

At the time of the 2013 guidelines, there was little evidence to recommend the use of medications other than statins.

Recent evidence

The IMPROVE-IT trial¹ was a double-blind, randomized trial involving 18,144 men and women who were older than 50 years and hospitalized for an acute coronary syndrome within the preceding 10 days. They were randomized to either simvastatin plus ezetimibe or simvastatin plus placebo. The primary endpoints were a composite of death from cardiovascular disease, a major coronary event (nonfatal MI, unstable angina requiring admission, or coronary revascularization), or nonfatal stroke. At 1 year, the mean LDL was 69.9 mg/dL in the simvastatin-monotherapy group and 53.2 mg/dL in the simvastatin-ezetimibe group (P under .001), representing a 24% decrease in LDL between the two groups. The rate of the primary endpoints was significantly lower in the simvastatin plus ezetimibe group with a hazard ratio of 0.936 (P = .016). The risk of MI was significantly decreased with an HR of 0.87 (P = .002), and the risk of ischemic stroke significantly decreased with an HR of 0.79 (P = .008). Prespecified safety endpoints showed no significant difference between the two groups.

The FOURIER trial² examined the PCSK-9 inhibitor, evolocumab. FOURIER was a randomized, double-blind, placebo-controlled study involving 27,564 patients with atherosclerotic cardiovascular disease and LDL levels of 70 mg/dL or higher who were receiving statin therapy (at least atorvastatin 20 mg or equivalent with/without ezetimibe). Patients were between 45 and 80 years old with a history of history of MI, nonhemorrhagic stroke, or symptomatic peripheral artery disease. Patients were randomized to receive subcutaneous injections of evolocumab or matching placebo. The primary endpoints were similar to that of IMPROVE-IT: a composite of cardiovascular death, myocardial infarction, stroke, unstable angina hospitalization, and coronary revascularization. The median LDL on entry was 92 mg/dL for both groups. At 48 weeks, the evolocumab group showed a 59% decrease in LDL, compared with placebo, with a decrease in median LDL from 92 mg/dL to 30 mg/dL. The primary endpoint occurred in 9.8% of the evolocumab group and 11.3% in the placebo group for a hazard ratio of 0.85 (P less than .001) representing a total risk reduction of 13.2%. The risk of MI or stroke and need for revascularization were significantly lower values in the evolocumab group, compared with placebo. Cardiovascular death did not show significant changes. There was no significant difference in rate of serious events.

The ODYSSEY trial³ reported on another PCSK-9 inhibitor, alirocumab, in a randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an ACS in the prior 12 months. At the median follow-up (2.8 years), the LDL of the alirocumab group was 53.3 mg/dL, compared with 101.4 mg/dL in the placebo group. The primary endpoints for cardiovascular risks were similar to those in the FOURIER trial: a risk of 9.5% in the alirocumab group and 11.1% in the placebo group for a total risk reduction of 14.4%. This suggests the class of PCSK-9 inhibitors have a strong correlation with reducing LDL levels 54%-59% and reducing major cardiac adverse events by 13%-15%.
 

Recommendations

The American College of Cardiology released a focused update that integrated the new evidence regarding the use of nonstatin therapy. The current focused update recommends an overall 50% or greater reduction in LDL for patients with clinical ASCVD. If this reduction is not achieved, ACC suggests that one consider the addition of nonstatin therapy with either ezetimibe or a PCSK-9 inhibitor.4 If a patient requires less than 25% additional LDL reduction, consider ezetimibe; if a patient requires more than 25% additional LDL reduction, consider a PCSK-9 inhibitor. Specifically, the guideline states: “If the patient still has less than 50% reduction in LDL-C (and may consider LDL-C above 70 mg/dL or non–HDL-C above 100 mg/dL), the patient and clinician should enter into a discussion focused on shared decision making regarding the addition of a nonstatin medication to the current regimen.”

The other group that is mentioned in the recommendations, with an acknowledgment that the evidence for benefit in primary prevention is not available, is individuals who have an LDL above 190 mg/dL even while compliant with a maximally effective statin regimen. The guidelines make further but less strong recommendations about a number of risk groups, but the largest and strongest change, based on strong evidence, is the recommendation to consider nonstatin therapy in individuals with established ASCVD, as described above.
 

Bottom line

Recent trials show significant reductions in LDL, leading to significant reductions in cardiovascular endpoints with ezetimibe and PCSK-9 inhibitors. This has led to an additional ACC recommendation to consider the use of nonstatin therapy in addition to maximal statin therapy in selected patients with established cardiovascular disease.

References

1. Cannon C et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-97.

2. Sabatine M et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-22.

3. ODYSSEY Outcomes: Results suggest use of PCSK9 inhibitor reduces CV events, LDL-C in ACS patients. Article from American College of Cardiology. ACC News Story. 2018 Mar 10.

4. Lloyd-Jones DM et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology task force on expert consensus decision pathways. J Am Coll Cardiol. 2017 Oct 3;70(14):1785-1822. Epub 2017 Sep 5.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Plako is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

Importance

While statins remain the foundation for treating high cholesterol in order to reduce cardiovascular risk, new evidence has lead to important revisions in the American Heart Association’s recommendations for treatment of hypercholesterolemia in patients at very high cardiovascular risk (secondary prevention) with the addition of specific nonstatin agents. We will briefly review the AHA 2013 guideline recommendations, the relevant new information, and the updated AHA recommendations.

American Heart Association 2013 guidelines

The 2013 American College of Cardiology/AHA cholesterol guidelines recommend either high- or moderate-intensity statin therapy for patients in the four statin benefit groups:

1. Adult patients older than 21 years of age with clinical atherosclerotic cardiovascular disease (ASCVD).

2. Adults older than 21 years of age with low-density lipoprotein cholesterol (LDL-C) above 190 mg/dL.

3. Adults aged 40-75 years without ASCVD but with diabetes and with LDL-C 70-189 mg/dL.

4. Adults aged 40-75 years without either ASCVD or diabetes, with LDL-C 70-189 mg/dL and an estimated 10-year risk for ASCVD of over 7.5% as determined by the Pooled Cohort Equations.

At the time of the 2013 guidelines, there was little evidence to recommend the use of medications other than statins.

Recent evidence

The IMPROVE-IT trial¹ was a double-blind, randomized trial involving 18,144 men and women who were older than 50 years and hospitalized for an acute coronary syndrome within the preceding 10 days. They were randomized to either simvastatin plus ezetimibe or simvastatin plus placebo. The primary endpoints were a composite of death from cardiovascular disease, a major coronary event (nonfatal MI, unstable angina requiring admission, or coronary revascularization), or nonfatal stroke. At 1 year, the mean LDL was 69.9 mg/dL in the simvastatin-monotherapy group and 53.2 mg/dL in the simvastatin-ezetimibe group (P under .001), representing a 24% decrease in LDL between the two groups. The rate of the primary endpoints was significantly lower in the simvastatin plus ezetimibe group with a hazard ratio of 0.936 (P = .016). The risk of MI was significantly decreased with an HR of 0.87 (P = .002), and the risk of ischemic stroke significantly decreased with an HR of 0.79 (P = .008). Prespecified safety endpoints showed no significant difference between the two groups.

The FOURIER trial² examined the PCSK-9 inhibitor, evolocumab. FOURIER was a randomized, double-blind, placebo-controlled study involving 27,564 patients with atherosclerotic cardiovascular disease and LDL levels of 70 mg/dL or higher who were receiving statin therapy (at least atorvastatin 20 mg or equivalent with/without ezetimibe). Patients were between 45 and 80 years old with a history of history of MI, nonhemorrhagic stroke, or symptomatic peripheral artery disease. Patients were randomized to receive subcutaneous injections of evolocumab or matching placebo. The primary endpoints were similar to that of IMPROVE-IT: a composite of cardiovascular death, myocardial infarction, stroke, unstable angina hospitalization, and coronary revascularization. The median LDL on entry was 92 mg/dL for both groups. At 48 weeks, the evolocumab group showed a 59% decrease in LDL, compared with placebo, with a decrease in median LDL from 92 mg/dL to 30 mg/dL. The primary endpoint occurred in 9.8% of the evolocumab group and 11.3% in the placebo group for a hazard ratio of 0.85 (P less than .001) representing a total risk reduction of 13.2%. The risk of MI or stroke and need for revascularization were significantly lower values in the evolocumab group, compared with placebo. Cardiovascular death did not show significant changes. There was no significant difference in rate of serious events.

The ODYSSEY trial³ reported on another PCSK-9 inhibitor, alirocumab, in a randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an ACS in the prior 12 months. At the median follow-up (2.8 years), the LDL of the alirocumab group was 53.3 mg/dL, compared with 101.4 mg/dL in the placebo group. The primary endpoints for cardiovascular risks were similar to those in the FOURIER trial: a risk of 9.5% in the alirocumab group and 11.1% in the placebo group for a total risk reduction of 14.4%. This suggests the class of PCSK-9 inhibitors have a strong correlation with reducing LDL levels 54%-59% and reducing major cardiac adverse events by 13%-15%.
 

Recommendations

The American College of Cardiology released a focused update that integrated the new evidence regarding the use of nonstatin therapy. The current focused update recommends an overall 50% or greater reduction in LDL for patients with clinical ASCVD. If this reduction is not achieved, ACC suggests that one consider the addition of nonstatin therapy with either ezetimibe or a PCSK-9 inhibitor.4 If a patient requires less than 25% additional LDL reduction, consider ezetimibe; if a patient requires more than 25% additional LDL reduction, consider a PCSK-9 inhibitor. Specifically, the guideline states: “If the patient still has less than 50% reduction in LDL-C (and may consider LDL-C above 70 mg/dL or non–HDL-C above 100 mg/dL), the patient and clinician should enter into a discussion focused on shared decision making regarding the addition of a nonstatin medication to the current regimen.”

The other group that is mentioned in the recommendations, with an acknowledgment that the evidence for benefit in primary prevention is not available, is individuals who have an LDL above 190 mg/dL even while compliant with a maximally effective statin regimen. The guidelines make further but less strong recommendations about a number of risk groups, but the largest and strongest change, based on strong evidence, is the recommendation to consider nonstatin therapy in individuals with established ASCVD, as described above.
 

Bottom line

Recent trials show significant reductions in LDL, leading to significant reductions in cardiovascular endpoints with ezetimibe and PCSK-9 inhibitors. This has led to an additional ACC recommendation to consider the use of nonstatin therapy in addition to maximal statin therapy in selected patients with established cardiovascular disease.

References

1. Cannon C et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-97.

2. Sabatine M et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-22.

3. ODYSSEY Outcomes: Results suggest use of PCSK9 inhibitor reduces CV events, LDL-C in ACS patients. Article from American College of Cardiology. ACC News Story. 2018 Mar 10.

4. Lloyd-Jones DM et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology task force on expert consensus decision pathways. J Am Coll Cardiol. 2017 Oct 3;70(14):1785-1822. Epub 2017 Sep 5.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Plako is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

Importance

While statins remain the foundation for treating high cholesterol in order to reduce cardiovascular risk, new evidence has lead to important revisions in the American Heart Association’s recommendations for treatment of hypercholesterolemia in patients at very high cardiovascular risk (secondary prevention) with the addition of specific nonstatin agents. We will briefly review the AHA 2013 guideline recommendations, the relevant new information, and the updated AHA recommendations.

American Heart Association 2013 guidelines

The 2013 American College of Cardiology/AHA cholesterol guidelines recommend either high- or moderate-intensity statin therapy for patients in the four statin benefit groups:

1. Adult patients older than 21 years of age with clinical atherosclerotic cardiovascular disease (ASCVD).

2. Adults older than 21 years of age with low-density lipoprotein cholesterol (LDL-C) above 190 mg/dL.

3. Adults aged 40-75 years without ASCVD but with diabetes and with LDL-C 70-189 mg/dL.

4. Adults aged 40-75 years without either ASCVD or diabetes, with LDL-C 70-189 mg/dL and an estimated 10-year risk for ASCVD of over 7.5% as determined by the Pooled Cohort Equations.

At the time of the 2013 guidelines, there was little evidence to recommend the use of medications other than statins.

Recent evidence

The IMPROVE-IT trial¹ was a double-blind, randomized trial involving 18,144 men and women who were older than 50 years and hospitalized for an acute coronary syndrome within the preceding 10 days. They were randomized to either simvastatin plus ezetimibe or simvastatin plus placebo. The primary endpoints were a composite of death from cardiovascular disease, a major coronary event (nonfatal MI, unstable angina requiring admission, or coronary revascularization), or nonfatal stroke. At 1 year, the mean LDL was 69.9 mg/dL in the simvastatin-monotherapy group and 53.2 mg/dL in the simvastatin-ezetimibe group (P under .001), representing a 24% decrease in LDL between the two groups. The rate of the primary endpoints was significantly lower in the simvastatin plus ezetimibe group with a hazard ratio of 0.936 (P = .016). The risk of MI was significantly decreased with an HR of 0.87 (P = .002), and the risk of ischemic stroke significantly decreased with an HR of 0.79 (P = .008). Prespecified safety endpoints showed no significant difference between the two groups.

The FOURIER trial² examined the PCSK-9 inhibitor, evolocumab. FOURIER was a randomized, double-blind, placebo-controlled study involving 27,564 patients with atherosclerotic cardiovascular disease and LDL levels of 70 mg/dL or higher who were receiving statin therapy (at least atorvastatin 20 mg or equivalent with/without ezetimibe). Patients were between 45 and 80 years old with a history of history of MI, nonhemorrhagic stroke, or symptomatic peripheral artery disease. Patients were randomized to receive subcutaneous injections of evolocumab or matching placebo. The primary endpoints were similar to that of IMPROVE-IT: a composite of cardiovascular death, myocardial infarction, stroke, unstable angina hospitalization, and coronary revascularization. The median LDL on entry was 92 mg/dL for both groups. At 48 weeks, the evolocumab group showed a 59% decrease in LDL, compared with placebo, with a decrease in median LDL from 92 mg/dL to 30 mg/dL. The primary endpoint occurred in 9.8% of the evolocumab group and 11.3% in the placebo group for a hazard ratio of 0.85 (P less than .001) representing a total risk reduction of 13.2%. The risk of MI or stroke and need for revascularization were significantly lower values in the evolocumab group, compared with placebo. Cardiovascular death did not show significant changes. There was no significant difference in rate of serious events.

The ODYSSEY trial³ reported on another PCSK-9 inhibitor, alirocumab, in a randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an ACS in the prior 12 months. At the median follow-up (2.8 years), the LDL of the alirocumab group was 53.3 mg/dL, compared with 101.4 mg/dL in the placebo group. The primary endpoints for cardiovascular risks were similar to those in the FOURIER trial: a risk of 9.5% in the alirocumab group and 11.1% in the placebo group for a total risk reduction of 14.4%. This suggests the class of PCSK-9 inhibitors have a strong correlation with reducing LDL levels 54%-59% and reducing major cardiac adverse events by 13%-15%.
 

Recommendations

The American College of Cardiology released a focused update that integrated the new evidence regarding the use of nonstatin therapy. The current focused update recommends an overall 50% or greater reduction in LDL for patients with clinical ASCVD. If this reduction is not achieved, ACC suggests that one consider the addition of nonstatin therapy with either ezetimibe or a PCSK-9 inhibitor.4 If a patient requires less than 25% additional LDL reduction, consider ezetimibe; if a patient requires more than 25% additional LDL reduction, consider a PCSK-9 inhibitor. Specifically, the guideline states: “If the patient still has less than 50% reduction in LDL-C (and may consider LDL-C above 70 mg/dL or non–HDL-C above 100 mg/dL), the patient and clinician should enter into a discussion focused on shared decision making regarding the addition of a nonstatin medication to the current regimen.”

The other group that is mentioned in the recommendations, with an acknowledgment that the evidence for benefit in primary prevention is not available, is individuals who have an LDL above 190 mg/dL even while compliant with a maximally effective statin regimen. The guidelines make further but less strong recommendations about a number of risk groups, but the largest and strongest change, based on strong evidence, is the recommendation to consider nonstatin therapy in individuals with established ASCVD, as described above.
 

Bottom line

Recent trials show significant reductions in LDL, leading to significant reductions in cardiovascular endpoints with ezetimibe and PCSK-9 inhibitors. This has led to an additional ACC recommendation to consider the use of nonstatin therapy in addition to maximal statin therapy in selected patients with established cardiovascular disease.

References

1. Cannon C et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-97.

2. Sabatine M et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-22.

3. ODYSSEY Outcomes: Results suggest use of PCSK9 inhibitor reduces CV events, LDL-C in ACS patients. Article from American College of Cardiology. ACC News Story. 2018 Mar 10.

4. Lloyd-Jones DM et al. 2017 Focused update of the 2016 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology task force on expert consensus decision pathways. J Am Coll Cardiol. 2017 Oct 3;70(14):1785-1822. Epub 2017 Sep 5.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Plako is a second-year resident in the family medicine residency program at Abington Jefferson Hospital.

The U.S. Preventive Services Task Force commissioned a systematic evidence review of 168 fair-good quality articles to examine newer evidence on screening for and treatment of osteoporotic fracture in women and men and update its 2011 guideline. They found convincing evidence that bone measurement tests and clinical risk assessment tools are accurate for predicting osteoporotic fractures in women. For postmenopausal women older than 65 years and those younger than 65 years with increased risk of osteoporosis, USPSTF found convincing evidence that screening can detect osteoporosis and that treatment can provide at least a moderate benefit in preventing fractures (grade B). For men, they report inadequate evidence on the benefits and harms of screening for osteoporosis to reduce the risk of fractures (I statement).

Importance

Osteoporosis leads to increased bone fragility and risk of fractures, specifically hip fractures, that are associated with limitations in ambulation, chronic pain, disability and loss of independence, and decreased quality of life: 21%-30% of those who suffer hip fractures die within 1 year. Osteoporosis is usually asymptomatic until a fracture occurs, thus preventing fractures is the main goal of an osteoporosis screening strategy. With the increasing life expectancy of the U.S. population, the potential preventable burden is likely to increase in future years.

Screening tests

The most commonly used test is central dual energy x-ray absorptiometry (DXA), which provides measurement of bone mineral density (BMD) of the hip and lumbar spine. Most treatment guidelines already use central DXA BMD to define osteoporosis and the threshold at which to start drug therapies for prevention. Other lower-cost and more accessible alternatives include peripheral DXA, which measures BMD at lower forearm and heel, and quantitative ultrasound (QUS), which also evaluates peripheral sites like the calcaneus. QUS does not measure BMD. USPSTF found that the harms associated with screening were small (mainly radiation exposure from DXA and opportunity costs).

Population and risk assessment

The review included adults older than 40 years of age, mostly postmenopausal women, without a history of previous low-trauma fractures, without conditions or medications that may cause secondary osteoporosis, and without increased risk of falls.

Patients at increased risk of osteoporotic fractures include those with parental history of hip fractures, low body weight, excessive alcohol consumption, and smokers. For postmenopausal women younger than 65 years of age with at least one risk factor, a reasonable approach to determine who should be screened with BMD is to use one of the various clinical risk assessment tools available. The most frequently studied tools in women are the Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-Assessment Tool (OST), and Simple Calculated Osteoporosis Risk Estimation (SCORE). The Fracture Risk Assessment (FRAX) tool calculates the 10-year risk of a major osteoporotic fracture (MOF) using clinical risk factors. For example, one approach is to perform BMD in women younger than 65 years with a FRAX risk greater than 8.4% (the FRAX risk of a 65-year-old woman of mean height and weight without major risk factors).

In men, the prevalence of osteoporosis (4.3%) is generally lower than in women (15.4%). In the absence of other risk factors, it is not till age 80 that the prevalence of osteoporosis in white men starts to reach that of a 65-year-old white woman. While men have similar risk factors as women described above, men with hypogonadism, history of cerebrovascular accident, and history of diabetes are also at increased risk of fracture.
 

Preventative measures to reduce osteoporotic fractures

Approved drug therapies. The majority of studies were conducted in postmenopausal women. Bisphosphonates, most commonly used and studied, significantly reduced vertebral and nonvertebral fractures but not hip fractures (possibly because of underpowered studies). Raloxifene and parathyroid hormone reduced vertebral fractures but not nonvertebral fractures. Denosumab significantly reduced all three types of fractures. A 2011 review identified that estrogen reduced vertebral fractures, but no new studies were identified for the current review. Data from the Women’s Health Initiative show that women receiving estrogen with or without progesterone had an elevated risk of stroke, venous thromboembolism, and gallbladder disease; their risk for urinary incontinence was increased during the first year of follow-up. In addition, women receiving estrogen plus progestin had a higher risk of invasive breast cancer, coronary heart disease, and probable dementia. The risk of serious adverse events, upper-gastrointestinal events, or cardiovascular events associated with the most common class of medications used, bisphosphonates, is small. Evidence on the effectiveness of medications to treat osteoporosis in men is lacking (only two studies conducted).

Exercise. Engagement in 120-300 minutes of weekly moderate-intensity aerobic activity can reduce the risk of hip fractures, and performance of weekly balance and muscle-strengthening activities can help prevent falls in older adults.

Supplements. In a separate recommendation, USPSTF recommends against daily supplementation with less than 400 IU of vitamin D and less than 1,000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. They found insufficient evidence on supplementation with higher doses of vitamin D and calcium in postmenopausal women, or at any dose in men and premenopausal women.
 

Recommendations from others

The National Osteoporosis Foundation and the International Society for Clinical Densitometry recommend BMD testing in all women older than 65 years, all men over 70 years, postmenopausal women younger than 65 years, and men aged 50-69 years with increased risk factors. The American Academy of Family Physicians recommends against DXA screening in women younger than 65 years and men younger than 70 years with no risk factors.
 

The bottom line

For all women older than 65 years and postmenopausal women younger than 65 years who are at increased risk, screen for and treat osteoporosis to prevent fractures. For men, there is insufficient evidence to screen.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

References

1. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2521-31.

2. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2532-51.
 

The U.S. Preventive Services Task Force commissioned a systematic evidence review of 168 fair-good quality articles to examine newer evidence on screening for and treatment of osteoporotic fracture in women and men and update its 2011 guideline. They found convincing evidence that bone measurement tests and clinical risk assessment tools are accurate for predicting osteoporotic fractures in women. For postmenopausal women older than 65 years and those younger than 65 years with increased risk of osteoporosis, USPSTF found convincing evidence that screening can detect osteoporosis and that treatment can provide at least a moderate benefit in preventing fractures (grade B). For men, they report inadequate evidence on the benefits and harms of screening for osteoporosis to reduce the risk of fractures (I statement).

Importance

Osteoporosis leads to increased bone fragility and risk of fractures, specifically hip fractures, that are associated with limitations in ambulation, chronic pain, disability and loss of independence, and decreased quality of life: 21%-30% of those who suffer hip fractures die within 1 year. Osteoporosis is usually asymptomatic until a fracture occurs, thus preventing fractures is the main goal of an osteoporosis screening strategy. With the increasing life expectancy of the U.S. population, the potential preventable burden is likely to increase in future years.

Screening tests

The most commonly used test is central dual energy x-ray absorptiometry (DXA), which provides measurement of bone mineral density (BMD) of the hip and lumbar spine. Most treatment guidelines already use central DXA BMD to define osteoporosis and the threshold at which to start drug therapies for prevention. Other lower-cost and more accessible alternatives include peripheral DXA, which measures BMD at lower forearm and heel, and quantitative ultrasound (QUS), which also evaluates peripheral sites like the calcaneus. QUS does not measure BMD. USPSTF found that the harms associated with screening were small (mainly radiation exposure from DXA and opportunity costs).

Population and risk assessment

The review included adults older than 40 years of age, mostly postmenopausal women, without a history of previous low-trauma fractures, without conditions or medications that may cause secondary osteoporosis, and without increased risk of falls.

Patients at increased risk of osteoporotic fractures include those with parental history of hip fractures, low body weight, excessive alcohol consumption, and smokers. For postmenopausal women younger than 65 years of age with at least one risk factor, a reasonable approach to determine who should be screened with BMD is to use one of the various clinical risk assessment tools available. The most frequently studied tools in women are the Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-Assessment Tool (OST), and Simple Calculated Osteoporosis Risk Estimation (SCORE). The Fracture Risk Assessment (FRAX) tool calculates the 10-year risk of a major osteoporotic fracture (MOF) using clinical risk factors. For example, one approach is to perform BMD in women younger than 65 years with a FRAX risk greater than 8.4% (the FRAX risk of a 65-year-old woman of mean height and weight without major risk factors).

In men, the prevalence of osteoporosis (4.3%) is generally lower than in women (15.4%). In the absence of other risk factors, it is not till age 80 that the prevalence of osteoporosis in white men starts to reach that of a 65-year-old white woman. While men have similar risk factors as women described above, men with hypogonadism, history of cerebrovascular accident, and history of diabetes are also at increased risk of fracture.
 

Preventative measures to reduce osteoporotic fractures

Approved drug therapies. The majority of studies were conducted in postmenopausal women. Bisphosphonates, most commonly used and studied, significantly reduced vertebral and nonvertebral fractures but not hip fractures (possibly because of underpowered studies). Raloxifene and parathyroid hormone reduced vertebral fractures but not nonvertebral fractures. Denosumab significantly reduced all three types of fractures. A 2011 review identified that estrogen reduced vertebral fractures, but no new studies were identified for the current review. Data from the Women’s Health Initiative show that women receiving estrogen with or without progesterone had an elevated risk of stroke, venous thromboembolism, and gallbladder disease; their risk for urinary incontinence was increased during the first year of follow-up. In addition, women receiving estrogen plus progestin had a higher risk of invasive breast cancer, coronary heart disease, and probable dementia. The risk of serious adverse events, upper-gastrointestinal events, or cardiovascular events associated with the most common class of medications used, bisphosphonates, is small. Evidence on the effectiveness of medications to treat osteoporosis in men is lacking (only two studies conducted).

Exercise. Engagement in 120-300 minutes of weekly moderate-intensity aerobic activity can reduce the risk of hip fractures, and performance of weekly balance and muscle-strengthening activities can help prevent falls in older adults.

Supplements. In a separate recommendation, USPSTF recommends against daily supplementation with less than 400 IU of vitamin D and less than 1,000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. They found insufficient evidence on supplementation with higher doses of vitamin D and calcium in postmenopausal women, or at any dose in men and premenopausal women.
 

Recommendations from others

The National Osteoporosis Foundation and the International Society for Clinical Densitometry recommend BMD testing in all women older than 65 years, all men over 70 years, postmenopausal women younger than 65 years, and men aged 50-69 years with increased risk factors. The American Academy of Family Physicians recommends against DXA screening in women younger than 65 years and men younger than 70 years with no risk factors.
 

The bottom line

For all women older than 65 years and postmenopausal women younger than 65 years who are at increased risk, screen for and treat osteoporosis to prevent fractures. For men, there is insufficient evidence to screen.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

References

1. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2521-31.

2. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2532-51.
 

The U.S. Preventive Services Task Force commissioned a systematic evidence review of 168 fair-good quality articles to examine newer evidence on screening for and treatment of osteoporotic fracture in women and men and update its 2011 guideline. They found convincing evidence that bone measurement tests and clinical risk assessment tools are accurate for predicting osteoporotic fractures in women. For postmenopausal women older than 65 years and those younger than 65 years with increased risk of osteoporosis, USPSTF found convincing evidence that screening can detect osteoporosis and that treatment can provide at least a moderate benefit in preventing fractures (grade B). For men, they report inadequate evidence on the benefits and harms of screening for osteoporosis to reduce the risk of fractures (I statement).

Importance

Osteoporosis leads to increased bone fragility and risk of fractures, specifically hip fractures, that are associated with limitations in ambulation, chronic pain, disability and loss of independence, and decreased quality of life: 21%-30% of those who suffer hip fractures die within 1 year. Osteoporosis is usually asymptomatic until a fracture occurs, thus preventing fractures is the main goal of an osteoporosis screening strategy. With the increasing life expectancy of the U.S. population, the potential preventable burden is likely to increase in future years.

Screening tests

The most commonly used test is central dual energy x-ray absorptiometry (DXA), which provides measurement of bone mineral density (BMD) of the hip and lumbar spine. Most treatment guidelines already use central DXA BMD to define osteoporosis and the threshold at which to start drug therapies for prevention. Other lower-cost and more accessible alternatives include peripheral DXA, which measures BMD at lower forearm and heel, and quantitative ultrasound (QUS), which also evaluates peripheral sites like the calcaneus. QUS does not measure BMD. USPSTF found that the harms associated with screening were small (mainly radiation exposure from DXA and opportunity costs).

Population and risk assessment

The review included adults older than 40 years of age, mostly postmenopausal women, without a history of previous low-trauma fractures, without conditions or medications that may cause secondary osteoporosis, and without increased risk of falls.

Patients at increased risk of osteoporotic fractures include those with parental history of hip fractures, low body weight, excessive alcohol consumption, and smokers. For postmenopausal women younger than 65 years of age with at least one risk factor, a reasonable approach to determine who should be screened with BMD is to use one of the various clinical risk assessment tools available. The most frequently studied tools in women are the Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-Assessment Tool (OST), and Simple Calculated Osteoporosis Risk Estimation (SCORE). The Fracture Risk Assessment (FRAX) tool calculates the 10-year risk of a major osteoporotic fracture (MOF) using clinical risk factors. For example, one approach is to perform BMD in women younger than 65 years with a FRAX risk greater than 8.4% (the FRAX risk of a 65-year-old woman of mean height and weight without major risk factors).

In men, the prevalence of osteoporosis (4.3%) is generally lower than in women (15.4%). In the absence of other risk factors, it is not till age 80 that the prevalence of osteoporosis in white men starts to reach that of a 65-year-old white woman. While men have similar risk factors as women described above, men with hypogonadism, history of cerebrovascular accident, and history of diabetes are also at increased risk of fracture.
 

Preventative measures to reduce osteoporotic fractures

Approved drug therapies. The majority of studies were conducted in postmenopausal women. Bisphosphonates, most commonly used and studied, significantly reduced vertebral and nonvertebral fractures but not hip fractures (possibly because of underpowered studies). Raloxifene and parathyroid hormone reduced vertebral fractures but not nonvertebral fractures. Denosumab significantly reduced all three types of fractures. A 2011 review identified that estrogen reduced vertebral fractures, but no new studies were identified for the current review. Data from the Women’s Health Initiative show that women receiving estrogen with or without progesterone had an elevated risk of stroke, venous thromboembolism, and gallbladder disease; their risk for urinary incontinence was increased during the first year of follow-up. In addition, women receiving estrogen plus progestin had a higher risk of invasive breast cancer, coronary heart disease, and probable dementia. The risk of serious adverse events, upper-gastrointestinal events, or cardiovascular events associated with the most common class of medications used, bisphosphonates, is small. Evidence on the effectiveness of medications to treat osteoporosis in men is lacking (only two studies conducted).

Exercise. Engagement in 120-300 minutes of weekly moderate-intensity aerobic activity can reduce the risk of hip fractures, and performance of weekly balance and muscle-strengthening activities can help prevent falls in older adults.

Supplements. In a separate recommendation, USPSTF recommends against daily supplementation with less than 400 IU of vitamin D and less than 1,000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. They found insufficient evidence on supplementation with higher doses of vitamin D and calcium in postmenopausal women, or at any dose in men and premenopausal women.
 

Recommendations from others

The National Osteoporosis Foundation and the International Society for Clinical Densitometry recommend BMD testing in all women older than 65 years, all men over 70 years, postmenopausal women younger than 65 years, and men aged 50-69 years with increased risk factors. The American Academy of Family Physicians recommends against DXA screening in women younger than 65 years and men younger than 70 years with no risk factors.
 

The bottom line

For all women older than 65 years and postmenopausal women younger than 65 years who are at increased risk, screen for and treat osteoporosis to prevent fractures. For men, there is insufficient evidence to screen.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

References

1. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2521-31.

2. U.S. Preventative Services Task Force. JAMA. 2018 Jun 26;319(24):2532-51.
 

The United States Preventive Services Task Force (USPSTF) commissioned a systematic evidence review of 62 randomized clinical trials with a total of 35,058 patients to gather evidence on the effectiveness and harms of primary care–relevant interventions to prevent falls in community-dwelling adults 65 years or older.¹This 2018 statement recommends exercise interventions (B recommendation), advises selective offering of multifactorial interventions based on individual circumstances (C recommendation), and discourages the use of vitamin D supplementation (D recommendation).² It thereby has updated its 2012 statement, in which exercise or physical therapy and vitamin D supplementation were recommended to prevent falls.

Importance

Scope of review

Out of the 62 randomized clinical trials, 65% of intervention studies targeted patients at high risk of falls; they were most commonly identified by history of prior falls, but mobility, gait, and balance impairment were often also considered. Specific medical diagnoses that could affect fall-related outcomes (osteoporosis, visual impairment, neurocognitive disorders) were excluded. This review did not look at the outcome of studies in populations who were vitamin D deficient because, in this population, vitamin D supplementation would be considered treatment rather than prevention. Of note, women constituted the majority in most studies.

Exercise interventions

USPSTF found five good-quality and 16 fair-quality studies, which altogether included a total of 7,297 patients, that reported on various exercise interventions to prevent falls; altogether, these studies included a total of 7,297 patients. Of the studies, 57% recruited populations at high risk for falls with a mean age ranging from 68 to 88 years. Exercise interventions included supervised individual classes, group classes, and physical therapy. The most common exercise component was gait, balance, and functional training; other common components included, in order of frequency, were resistance training, flexibility training, and endurance training. Most common frequency and duration were three sessions per week for 12 months. Exercise interventions reduced the number of persons experiencing a fall (relative risk 0.89; 95% confidence interval, 0.81-0.97), reduced the number of injurious falls (incidence rate ratio, 0.81; 95% CI, 0.73-0.90), and revealed a statistically insignificant reduction in the number of falls. Reported adverse events were minor and most commonly included pain or bruising related to exercise.

Multifactorial interventions

USPSTF found seven good-quality and 19 fair-quality studies that reported on multifactorial interventions; altogether, these studies included a total of 15,506 patients. Of the studies, 73% recruited populations at high risk for falls, and the mean age ranged from 71.9 to 85 years. Multifactorial interventions had two components:

• Initial assessment to screen for modifiable risk factors for falls (multidisciplinary comprehensive geriatric assessment or specific assessment that evaluated various factors, such as balance, gait, vision, cardiovascular health, medication, environment, cognition, and psychological health).
• Subsequent customized interventions (group or individual exercise, cognitive-behavioral therapy, nutrition, environmental modification, physical or occupational therapy, social or community services, and referral to specialists).

While studies found that multifactorial interventions reduced the number of falls (IRR, 0.79; 95% CI, 0.68-0.91), they did not reduce the number of people who experienced a fall (RR, 0.95; 95% CI, 0.89-1.01) or an injurious fall (RR, 0.94; 95% CI, 0.85-1.03). Four studies reported minor harm, mostly bruising, from exercise. Therefore, USPSTF has recommended that clinicians take into consideration patient’s medical history (including prior falls and comorbidities) to selectively offer multifactorial interventions.

Vitamin D supplementation

USPSTF found four good-quality and three fair-quality studies that reported on the effect of vitamin D supplementation on the prevention of falls; altogether, these studies included a total of 7,531 patients. Of the studies, 43% recruited populations at high risk for falls. The mean age ranged from 71 to 76.8 years, and mean serum 25-OH vitamin D levels ranged from 26.4 to 31.8 ng/mL. Vitamin D formulations and dosages varied among trials from 700 IU/day to 150,000 IU/3 months to 500,000 IU/year. Pooled analyses did not show a significant reduction in falls (IRR, 0.97; 95% CI, 0.79-1.20) or the number of persons experiencing a fall (RR, 0.97; 95% CI, 0.88-1.08). Only two trials reported on injurious falls; one reported an increase and the other reported no statistically significant difference. One study using high doses of Vitamin D supplementation (500,000 IU per year) showed statistically significant increase in all three endpoints.

Recommendation of others for fall prevention

The National Institution of Aging has emphasized exercise for strength and balance, monitoring for environmental hazards, and hearing and vision care, as well as medication management. The American Geriatric Society (AGS) has recommended asking about prior falls annually and assessing gait and balance on those who have experienced a fall. The AGS also has recommended strength and gait training, environmental modification, medication management, and vitamin D supplementation of at least 800 IU/day for those vitamin D deficient or at increased risk of falls. The Center for Disease Control and Prevention recommends STEADI (Stopping Elderly Accidents, Deaths & Injuries), a coordinated approach to implement the AGS’s clinical practice guidelines. The American Academy of Family Physicians recommends exercise or physical therapy and vitamin D supplementation.

The bottom line

Regarding reduction of falls, the USPSTF found adequate evidence that exercise interventions confer a moderate net benefit, multifactorial interventions have a small net benefit, and vitamin D supplementation offers no net benefit in preventing falls.

References

1. Guirquis-Blake JM et al. JAMA. 2018 Apr 24;319(16):1705-16.

2. U.S. Preventive Services Task Force et al. JAMA. 2018 Apr 24;319(16):1696-1704.
 

Dr. Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

.

The United States Preventive Services Task Force (USPSTF) commissioned a systematic evidence review of 62 randomized clinical trials with a total of 35,058 patients to gather evidence on the effectiveness and harms of primary care–relevant interventions to prevent falls in community-dwelling adults 65 years or older.¹This 2018 statement recommends exercise interventions (B recommendation), advises selective offering of multifactorial interventions based on individual circumstances (C recommendation), and discourages the use of vitamin D supplementation (D recommendation).² It thereby has updated its 2012 statement, in which exercise or physical therapy and vitamin D supplementation were recommended to prevent falls.

Importance

Scope of review

Out of the 62 randomized clinical trials, 65% of intervention studies targeted patients at high risk of falls; they were most commonly identified by history of prior falls, but mobility, gait, and balance impairment were often also considered. Specific medical diagnoses that could affect fall-related outcomes (osteoporosis, visual impairment, neurocognitive disorders) were excluded. This review did not look at the outcome of studies in populations who were vitamin D deficient because, in this population, vitamin D supplementation would be considered treatment rather than prevention. Of note, women constituted the majority in most studies.

Exercise interventions

USPSTF found five good-quality and 16 fair-quality studies, which altogether included a total of 7,297 patients, that reported on various exercise interventions to prevent falls; altogether, these studies included a total of 7,297 patients. Of the studies, 57% recruited populations at high risk for falls with a mean age ranging from 68 to 88 years. Exercise interventions included supervised individual classes, group classes, and physical therapy. The most common exercise component was gait, balance, and functional training; other common components included, in order of frequency, were resistance training, flexibility training, and endurance training. Most common frequency and duration were three sessions per week for 12 months. Exercise interventions reduced the number of persons experiencing a fall (relative risk 0.89; 95% confidence interval, 0.81-0.97), reduced the number of injurious falls (incidence rate ratio, 0.81; 95% CI, 0.73-0.90), and revealed a statistically insignificant reduction in the number of falls. Reported adverse events were minor and most commonly included pain or bruising related to exercise.

Multifactorial interventions

USPSTF found seven good-quality and 19 fair-quality studies that reported on multifactorial interventions; altogether, these studies included a total of 15,506 patients. Of the studies, 73% recruited populations at high risk for falls, and the mean age ranged from 71.9 to 85 years. Multifactorial interventions had two components:

• Initial assessment to screen for modifiable risk factors for falls (multidisciplinary comprehensive geriatric assessment or specific assessment that evaluated various factors, such as balance, gait, vision, cardiovascular health, medication, environment, cognition, and psychological health).
• Subsequent customized interventions (group or individual exercise, cognitive-behavioral therapy, nutrition, environmental modification, physical or occupational therapy, social or community services, and referral to specialists).

While studies found that multifactorial interventions reduced the number of falls (IRR, 0.79; 95% CI, 0.68-0.91), they did not reduce the number of people who experienced a fall (RR, 0.95; 95% CI, 0.89-1.01) or an injurious fall (RR, 0.94; 95% CI, 0.85-1.03). Four studies reported minor harm, mostly bruising, from exercise. Therefore, USPSTF has recommended that clinicians take into consideration patient’s medical history (including prior falls and comorbidities) to selectively offer multifactorial interventions.

Vitamin D supplementation

USPSTF found four good-quality and three fair-quality studies that reported on the effect of vitamin D supplementation on the prevention of falls; altogether, these studies included a total of 7,531 patients. Of the studies, 43% recruited populations at high risk for falls. The mean age ranged from 71 to 76.8 years, and mean serum 25-OH vitamin D levels ranged from 26.4 to 31.8 ng/mL. Vitamin D formulations and dosages varied among trials from 700 IU/day to 150,000 IU/3 months to 500,000 IU/year. Pooled analyses did not show a significant reduction in falls (IRR, 0.97; 95% CI, 0.79-1.20) or the number of persons experiencing a fall (RR, 0.97; 95% CI, 0.88-1.08). Only two trials reported on injurious falls; one reported an increase and the other reported no statistically significant difference. One study using high doses of Vitamin D supplementation (500,000 IU per year) showed statistically significant increase in all three endpoints.

Recommendation of others for fall prevention

The National Institution of Aging has emphasized exercise for strength and balance, monitoring for environmental hazards, and hearing and vision care, as well as medication management. The American Geriatric Society (AGS) has recommended asking about prior falls annually and assessing gait and balance on those who have experienced a fall. The AGS also has recommended strength and gait training, environmental modification, medication management, and vitamin D supplementation of at least 800 IU/day for those vitamin D deficient or at increased risk of falls. The Center for Disease Control and Prevention recommends STEADI (Stopping Elderly Accidents, Deaths & Injuries), a coordinated approach to implement the AGS’s clinical practice guidelines. The American Academy of Family Physicians recommends exercise or physical therapy and vitamin D supplementation.

The bottom line

Regarding reduction of falls, the USPSTF found adequate evidence that exercise interventions confer a moderate net benefit, multifactorial interventions have a small net benefit, and vitamin D supplementation offers no net benefit in preventing falls.

References

1. Guirquis-Blake JM et al. JAMA. 2018 Apr 24;319(16):1705-16.

2. U.S. Preventive Services Task Force et al. JAMA. 2018 Apr 24;319(16):1696-1704.
 

Dr. Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

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The United States Preventive Services Task Force (USPSTF) commissioned a systematic evidence review of 62 randomized clinical trials with a total of 35,058 patients to gather evidence on the effectiveness and harms of primary care–relevant interventions to prevent falls in community-dwelling adults 65 years or older.¹This 2018 statement recommends exercise interventions (B recommendation), advises selective offering of multifactorial interventions based on individual circumstances (C recommendation), and discourages the use of vitamin D supplementation (D recommendation).² It thereby has updated its 2012 statement, in which exercise or physical therapy and vitamin D supplementation were recommended to prevent falls.

Importance

Scope of review

Out of the 62 randomized clinical trials, 65% of intervention studies targeted patients at high risk of falls; they were most commonly identified by history of prior falls, but mobility, gait, and balance impairment were often also considered. Specific medical diagnoses that could affect fall-related outcomes (osteoporosis, visual impairment, neurocognitive disorders) were excluded. This review did not look at the outcome of studies in populations who were vitamin D deficient because, in this population, vitamin D supplementation would be considered treatment rather than prevention. Of note, women constituted the majority in most studies.

Exercise interventions

USPSTF found five good-quality and 16 fair-quality studies, which altogether included a total of 7,297 patients, that reported on various exercise interventions to prevent falls; altogether, these studies included a total of 7,297 patients. Of the studies, 57% recruited populations at high risk for falls with a mean age ranging from 68 to 88 years. Exercise interventions included supervised individual classes, group classes, and physical therapy. The most common exercise component was gait, balance, and functional training; other common components included, in order of frequency, were resistance training, flexibility training, and endurance training. Most common frequency and duration were three sessions per week for 12 months. Exercise interventions reduced the number of persons experiencing a fall (relative risk 0.89; 95% confidence interval, 0.81-0.97), reduced the number of injurious falls (incidence rate ratio, 0.81; 95% CI, 0.73-0.90), and revealed a statistically insignificant reduction in the number of falls. Reported adverse events were minor and most commonly included pain or bruising related to exercise.

Multifactorial interventions

USPSTF found seven good-quality and 19 fair-quality studies that reported on multifactorial interventions; altogether, these studies included a total of 15,506 patients. Of the studies, 73% recruited populations at high risk for falls, and the mean age ranged from 71.9 to 85 years. Multifactorial interventions had two components:

• Initial assessment to screen for modifiable risk factors for falls (multidisciplinary comprehensive geriatric assessment or specific assessment that evaluated various factors, such as balance, gait, vision, cardiovascular health, medication, environment, cognition, and psychological health).
• Subsequent customized interventions (group or individual exercise, cognitive-behavioral therapy, nutrition, environmental modification, physical or occupational therapy, social or community services, and referral to specialists).

While studies found that multifactorial interventions reduced the number of falls (IRR, 0.79; 95% CI, 0.68-0.91), they did not reduce the number of people who experienced a fall (RR, 0.95; 95% CI, 0.89-1.01) or an injurious fall (RR, 0.94; 95% CI, 0.85-1.03). Four studies reported minor harm, mostly bruising, from exercise. Therefore, USPSTF has recommended that clinicians take into consideration patient’s medical history (including prior falls and comorbidities) to selectively offer multifactorial interventions.

Vitamin D supplementation

USPSTF found four good-quality and three fair-quality studies that reported on the effect of vitamin D supplementation on the prevention of falls; altogether, these studies included a total of 7,531 patients. Of the studies, 43% recruited populations at high risk for falls. The mean age ranged from 71 to 76.8 years, and mean serum 25-OH vitamin D levels ranged from 26.4 to 31.8 ng/mL. Vitamin D formulations and dosages varied among trials from 700 IU/day to 150,000 IU/3 months to 500,000 IU/year. Pooled analyses did not show a significant reduction in falls (IRR, 0.97; 95% CI, 0.79-1.20) or the number of persons experiencing a fall (RR, 0.97; 95% CI, 0.88-1.08). Only two trials reported on injurious falls; one reported an increase and the other reported no statistically significant difference. One study using high doses of Vitamin D supplementation (500,000 IU per year) showed statistically significant increase in all three endpoints.

Recommendation of others for fall prevention

The National Institution of Aging has emphasized exercise for strength and balance, monitoring for environmental hazards, and hearing and vision care, as well as medication management. The American Geriatric Society (AGS) has recommended asking about prior falls annually and assessing gait and balance on those who have experienced a fall. The AGS also has recommended strength and gait training, environmental modification, medication management, and vitamin D supplementation of at least 800 IU/day for those vitamin D deficient or at increased risk of falls. The Center for Disease Control and Prevention recommends STEADI (Stopping Elderly Accidents, Deaths & Injuries), a coordinated approach to implement the AGS’s clinical practice guidelines. The American Academy of Family Physicians recommends exercise or physical therapy and vitamin D supplementation.

The bottom line

Regarding reduction of falls, the USPSTF found adequate evidence that exercise interventions confer a moderate net benefit, multifactorial interventions have a small net benefit, and vitamin D supplementation offers no net benefit in preventing falls.

References

1. Guirquis-Blake JM et al. JAMA. 2018 Apr 24;319(16):1705-16.

2. U.S. Preventive Services Task Force et al. JAMA. 2018 Apr 24;319(16):1696-1704.
 

Dr. Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

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Guidelines issued jointly by the Endocrine Society and the European Society for Endocrinology provide clinicians with a clear consensus approach to male hypogonadism, commonly referred to by patients as “low T.” Hypogonadism results from “the failure of the testes to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic-pituitary-testicular axis,” according to the definition that serves as the basis for the guidelines.

Diagnosis

The signs and symptoms of hypogonadism are often nonspecific and include decreased energy, depressed mood, poor concentration and memory, sleep disturbance, mild normocytic normochromic anemia, reduced muscle bulk and strength, increased body fat, reduced libido, decreased erections, gynecomastia, low-trauma fractures, and loss of body hair. The diagnosis of hypogonadism is made when there are signs and symptoms of testosterone deficiency and of unequivocally and consistently low serum total testosterone and/or free testosterone concentrations.

Serum testosterone concentrations have diurnal variations, with values peaking in the morning. In addition, food intake suppresses testosterone concentrations. Therefore, testosterone levels should be measured in the morning after an overnight fast. Low testosterone concentrations need to be confirmed before making the diagnosis of hypogonadism because 30% of men with an initial testosterone concentration in the hypogonadal range have a normal testosterone concentration on repeat measurement. In addition, testosterone concentrations are not accurate in patients recovering from acute illness or taking medications known to suppress testosterone.

Testing of free testosterone and sex hormone–binding globulin (SHBG) may be considered in patients at risk for increased or decreased SHBG, including the obese, men with diabetes, the elderly, those with HIV or liver disease, or those taking estrogens and medications that may affect SHBG.

In individuals with low testosterone levels, a serum FSH and LH should be ordered to differentiate primary from secondary hypogonadism. Middle-aged and older men with secondary hypogonadism have a low prevalence of hypothalamic/pituitary abnormalities.

Treatment

In patients found to have low testosterone with signs and symptoms of testosterone deficiency, testosterone therapy is recommended to induce and maintain secondary sex characteristics and correct the symptoms of testosterone deficiency. Testosterone-replacement therapy in men with low testosterone levels leads to a small but statistically significant improvement in libido, erectile function, sexual activity or satisfaction, muscle mass, and bone density but does not lead to improvements in energy and mood.

Testosterone replacement should not be done in patient’s planning fertility in the near future, those with prostate or breast cancer, a palpable prostate nodule, a prostate-specific antigen (PSA) level greater than 4 ng/mL, a PSA greater than 3 ng/mL with high risk for prostate cancer, high hematocrit, untreated obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, MI or stroke within the last 6 months, or thrombophilia.

In men undergoing therapy, there is a higher frequency of erythrocytosis (hematocrit greater than 54%; relative risk, 8.14) but no increase in lower urinary tract symptoms. The benefit and risk of regular prostate cancer screening should be discussed prior to starting therapy with men aged 40-69 years with an increased risk of prostate cancer and with all men aged 55-69 years. For those who desire prostate cancer screening, PSA levels should be checked prior to starting therapy, and a digital prostate examination should be done at baseline and at 3-12 months after starting testosterone treatment. After 1 year, prostate cancer screening can be done per standard guidelines.

The decision about therapy in men older than 65 years is challenging because testosterone levels normally decline with age. It is not necessary to prescribe testosterone routinely to men older than 65 years with only low testosterone, and treatment should be reserved for those with symptoms along with low testosterone concentrations.

Men with HIV with low testosterone concentrations and weight loss can be treated with testosterone to induce and maintain body weight and lean muscle mass.
 

Monitoring

Patients should be evaluated 3-6 months after initiating treatment to see whether symptoms have improved, to see whether there have been adverse reactions, and to check labs.

Serum testosterone should be checked and the dose of testosterone replacement should be adjusted to maintain the serum testosterone level in the mid-normal range for healthy young men. Serum testosterone should be drawn at different times for different formulations – for instance, it should be checked 2-8 hours following a gel application.

Hematocrit should be checked at baseline and 3-6 months into treatment. If hematocrit is greater than 54%, therapy should be held until hematocrit decreases and then restarted at a reduced dose. Screening for prostate cancer should be done if that was decided upon during discussion with the patient. Further urologic evaluation is indicated in men who, during the first year of treatment, develop an increase from baseline PSA greater than 1.4 ng/mL, have a repeat PSA over 4 ng/mL, or have a prostatic abnormality on digital rectal exam.

The bottom line

Hypogonadism is common and presents diagnostic challenges because of nonspecific signs and symptoms. Serum testosterone should be checked on a first-morning fasting specimen. Low testosterone concentrations need to be confirmed before making the diagnosis and should be followed by checking FSH and LH. For those with signs and symptoms of hypogonadism and persistently low testosterone, testosterone replacement therapy can be beneficial, with a goal of maintaining serum testosterone in the mid-range of normal.

Reference

Bhasin S et al. Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 May;103(5):1-30.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Hurchick is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Guidelines issued jointly by the Endocrine Society and the European Society for Endocrinology provide clinicians with a clear consensus approach to male hypogonadism, commonly referred to by patients as “low T.” Hypogonadism results from “the failure of the testes to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic-pituitary-testicular axis,” according to the definition that serves as the basis for the guidelines.

Diagnosis

The signs and symptoms of hypogonadism are often nonspecific and include decreased energy, depressed mood, poor concentration and memory, sleep disturbance, mild normocytic normochromic anemia, reduced muscle bulk and strength, increased body fat, reduced libido, decreased erections, gynecomastia, low-trauma fractures, and loss of body hair. The diagnosis of hypogonadism is made when there are signs and symptoms of testosterone deficiency and of unequivocally and consistently low serum total testosterone and/or free testosterone concentrations.

Serum testosterone concentrations have diurnal variations, with values peaking in the morning. In addition, food intake suppresses testosterone concentrations. Therefore, testosterone levels should be measured in the morning after an overnight fast. Low testosterone concentrations need to be confirmed before making the diagnosis of hypogonadism because 30% of men with an initial testosterone concentration in the hypogonadal range have a normal testosterone concentration on repeat measurement. In addition, testosterone concentrations are not accurate in patients recovering from acute illness or taking medications known to suppress testosterone.

Testing of free testosterone and sex hormone–binding globulin (SHBG) may be considered in patients at risk for increased or decreased SHBG, including the obese, men with diabetes, the elderly, those with HIV or liver disease, or those taking estrogens and medications that may affect SHBG.

In individuals with low testosterone levels, a serum FSH and LH should be ordered to differentiate primary from secondary hypogonadism. Middle-aged and older men with secondary hypogonadism have a low prevalence of hypothalamic/pituitary abnormalities.

Treatment

In patients found to have low testosterone with signs and symptoms of testosterone deficiency, testosterone therapy is recommended to induce and maintain secondary sex characteristics and correct the symptoms of testosterone deficiency. Testosterone-replacement therapy in men with low testosterone levels leads to a small but statistically significant improvement in libido, erectile function, sexual activity or satisfaction, muscle mass, and bone density but does not lead to improvements in energy and mood.

Testosterone replacement should not be done in patient’s planning fertility in the near future, those with prostate or breast cancer, a palpable prostate nodule, a prostate-specific antigen (PSA) level greater than 4 ng/mL, a PSA greater than 3 ng/mL with high risk for prostate cancer, high hematocrit, untreated obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, MI or stroke within the last 6 months, or thrombophilia.

In men undergoing therapy, there is a higher frequency of erythrocytosis (hematocrit greater than 54%; relative risk, 8.14) but no increase in lower urinary tract symptoms. The benefit and risk of regular prostate cancer screening should be discussed prior to starting therapy with men aged 40-69 years with an increased risk of prostate cancer and with all men aged 55-69 years. For those who desire prostate cancer screening, PSA levels should be checked prior to starting therapy, and a digital prostate examination should be done at baseline and at 3-12 months after starting testosterone treatment. After 1 year, prostate cancer screening can be done per standard guidelines.

The decision about therapy in men older than 65 years is challenging because testosterone levels normally decline with age. It is not necessary to prescribe testosterone routinely to men older than 65 years with only low testosterone, and treatment should be reserved for those with symptoms along with low testosterone concentrations.

Men with HIV with low testosterone concentrations and weight loss can be treated with testosterone to induce and maintain body weight and lean muscle mass.
 

Monitoring

Patients should be evaluated 3-6 months after initiating treatment to see whether symptoms have improved, to see whether there have been adverse reactions, and to check labs.

Serum testosterone should be checked and the dose of testosterone replacement should be adjusted to maintain the serum testosterone level in the mid-normal range for healthy young men. Serum testosterone should be drawn at different times for different formulations – for instance, it should be checked 2-8 hours following a gel application.

Hematocrit should be checked at baseline and 3-6 months into treatment. If hematocrit is greater than 54%, therapy should be held until hematocrit decreases and then restarted at a reduced dose. Screening for prostate cancer should be done if that was decided upon during discussion with the patient. Further urologic evaluation is indicated in men who, during the first year of treatment, develop an increase from baseline PSA greater than 1.4 ng/mL, have a repeat PSA over 4 ng/mL, or have a prostatic abnormality on digital rectal exam.

The bottom line

Hypogonadism is common and presents diagnostic challenges because of nonspecific signs and symptoms. Serum testosterone should be checked on a first-morning fasting specimen. Low testosterone concentrations need to be confirmed before making the diagnosis and should be followed by checking FSH and LH. For those with signs and symptoms of hypogonadism and persistently low testosterone, testosterone replacement therapy can be beneficial, with a goal of maintaining serum testosterone in the mid-range of normal.

Reference

Bhasin S et al. Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 May;103(5):1-30.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Hurchick is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Guidelines issued jointly by the Endocrine Society and the European Society for Endocrinology provide clinicians with a clear consensus approach to male hypogonadism, commonly referred to by patients as “low T.” Hypogonadism results from “the failure of the testes to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic-pituitary-testicular axis,” according to the definition that serves as the basis for the guidelines.

Diagnosis

The signs and symptoms of hypogonadism are often nonspecific and include decreased energy, depressed mood, poor concentration and memory, sleep disturbance, mild normocytic normochromic anemia, reduced muscle bulk and strength, increased body fat, reduced libido, decreased erections, gynecomastia, low-trauma fractures, and loss of body hair. The diagnosis of hypogonadism is made when there are signs and symptoms of testosterone deficiency and of unequivocally and consistently low serum total testosterone and/or free testosterone concentrations.

Serum testosterone concentrations have diurnal variations, with values peaking in the morning. In addition, food intake suppresses testosterone concentrations. Therefore, testosterone levels should be measured in the morning after an overnight fast. Low testosterone concentrations need to be confirmed before making the diagnosis of hypogonadism because 30% of men with an initial testosterone concentration in the hypogonadal range have a normal testosterone concentration on repeat measurement. In addition, testosterone concentrations are not accurate in patients recovering from acute illness or taking medications known to suppress testosterone.

Testing of free testosterone and sex hormone–binding globulin (SHBG) may be considered in patients at risk for increased or decreased SHBG, including the obese, men with diabetes, the elderly, those with HIV or liver disease, or those taking estrogens and medications that may affect SHBG.

In individuals with low testosterone levels, a serum FSH and LH should be ordered to differentiate primary from secondary hypogonadism. Middle-aged and older men with secondary hypogonadism have a low prevalence of hypothalamic/pituitary abnormalities.

Treatment

In patients found to have low testosterone with signs and symptoms of testosterone deficiency, testosterone therapy is recommended to induce and maintain secondary sex characteristics and correct the symptoms of testosterone deficiency. Testosterone-replacement therapy in men with low testosterone levels leads to a small but statistically significant improvement in libido, erectile function, sexual activity or satisfaction, muscle mass, and bone density but does not lead to improvements in energy and mood.

Testosterone replacement should not be done in patient’s planning fertility in the near future, those with prostate or breast cancer, a palpable prostate nodule, a prostate-specific antigen (PSA) level greater than 4 ng/mL, a PSA greater than 3 ng/mL with high risk for prostate cancer, high hematocrit, untreated obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, MI or stroke within the last 6 months, or thrombophilia.

In men undergoing therapy, there is a higher frequency of erythrocytosis (hematocrit greater than 54%; relative risk, 8.14) but no increase in lower urinary tract symptoms. The benefit and risk of regular prostate cancer screening should be discussed prior to starting therapy with men aged 40-69 years with an increased risk of prostate cancer and with all men aged 55-69 years. For those who desire prostate cancer screening, PSA levels should be checked prior to starting therapy, and a digital prostate examination should be done at baseline and at 3-12 months after starting testosterone treatment. After 1 year, prostate cancer screening can be done per standard guidelines.

The decision about therapy in men older than 65 years is challenging because testosterone levels normally decline with age. It is not necessary to prescribe testosterone routinely to men older than 65 years with only low testosterone, and treatment should be reserved for those with symptoms along with low testosterone concentrations.

Men with HIV with low testosterone concentrations and weight loss can be treated with testosterone to induce and maintain body weight and lean muscle mass.
 

Monitoring

Patients should be evaluated 3-6 months after initiating treatment to see whether symptoms have improved, to see whether there have been adverse reactions, and to check labs.

Serum testosterone should be checked and the dose of testosterone replacement should be adjusted to maintain the serum testosterone level in the mid-normal range for healthy young men. Serum testosterone should be drawn at different times for different formulations – for instance, it should be checked 2-8 hours following a gel application.

Hematocrit should be checked at baseline and 3-6 months into treatment. If hematocrit is greater than 54%, therapy should be held until hematocrit decreases and then restarted at a reduced dose. Screening for prostate cancer should be done if that was decided upon during discussion with the patient. Further urologic evaluation is indicated in men who, during the first year of treatment, develop an increase from baseline PSA greater than 1.4 ng/mL, have a repeat PSA over 4 ng/mL, or have a prostatic abnormality on digital rectal exam.

The bottom line

Hypogonadism is common and presents diagnostic challenges because of nonspecific signs and symptoms. Serum testosterone should be checked on a first-morning fasting specimen. Low testosterone concentrations need to be confirmed before making the diagnosis and should be followed by checking FSH and LH. For those with signs and symptoms of hypogonadism and persistently low testosterone, testosterone replacement therapy can be beneficial, with a goal of maintaining serum testosterone in the mid-range of normal.

Reference

Bhasin S et al. Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 May;103(5):1-30.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Hurchick is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Significant changes have occurred in the updated American Heart Association Stroke Council’s recommendations for early management of acute ischemic stroke (AIS). Conceptually, early management can be separated into initial triage and decisions about intervention to restore blood flow with thrombolysis or mechanical thrombectomy. If reperfusion therapy is not appropriate, then the focus is on management to minimize further damage from the stroke, decrease the likelihood of recurrence, and lessen secondary problems related to the stroke.

All patients with AIS should receive noncontrast CT to determine if there is evidence of a hemorrhagic stroke and, if such evidence exists, than the patient is not a candidate for thrombolysis. Intravenous alteplase should be considered for patients who present within 3 hours of stroke onset and for selected patients presenting between 3-4.5 hours after stroke onset (for more details, see Table 6 in the guidelines). Selected patients with AIS who present within 6-24 hours of last time they were known to be normal and who have large vessel occlusion in the anterior circulation, may be candidates for mechanical thrombectomy in specialized centers. Patients who are not candidates for acute interventions should then be managed according to early stroke management guidelines.

Early stroke management for patients with AIS admitted to medical floors involves attention to blood pressure, glucose, and antiplatelet therapy. For patients with blood pressure lower than 220/120 mm Hg who did not receive IV alteplase or thrombectomy, treatment of hypertension in the first 48-72 hours after an AIS does not change the outcome. It is reasonable when patients have BP greater than or equal to 220/120 mm Hg, to lower blood pressure by 15% during the first 24 hours after onset of stroke. Starting or restarting antihypertensive therapy during hospitalization in patients with blood pressure higher than 140/90 mm Hg who are neurologically stable improves long-term blood pressure control and is considered a reasonable strategy.

For patients with noncardioembolic AIS, the use of antiplatelet agents rather than oral anticoagulation is recommended. Patients should be treated with aspirin 160 mg-325 mg within 24-48 hours of presentation. In patients unsafe or unable to swallow, rectal or nasogastric administration is recommended. In patients with minor stroke, 21 days of dual-antiplatelet therapy (aspirin and clopidogrel) started within 24 hours can decrease stroke recurrence for the first 90 days after a stroke. This recommendation is based on a single study, the CHANCE trial, in a homogeneous population in China, and its generalizability is not known. If a patient had an AIS while already on aspirin, there is some evidence supporting a decreased risk of major cardiovascular events and recurrent stroke in patients switching to an alternative antiplatelet agent or combination antiplatelet therapy. Because of methodologic issues in the those studies, the guideline concludes that, for those already on aspirin, it is of unclear benefit to increase the dose of aspirin, switch to a different antiplatelet agent, or add a second antiplatelet agent. Switching to warfarin is not beneficial for secondary stroke prevention. High-dose statin therapy should be initiated. For patients with AIS in the setting of atrial fibrillation, oral anticoagulation can be started within 4-14 days after the stroke. One study showed that anticoagulation should not be started before 4 days after the stroke, with a hazard ratio of 0.53 for starting anticoagulation at 4-14 days, compared with less than 4 days.

Hyperglycemia should be controlled to a range of 140-180 mg/dL, because higher values are associated with worse outcomes. Oxygen should be used if needed to maintain oxygen saturation greater than 94%. High-intensity statin therapy should be used, and smoking cessation is strongly encouraged for those who use tobacco, with avoidance of secondhand smoke whenever possible.

Patients should be screened for dysphagia before taking anything per oral, including medications. A nasogastric tube may be considered within the first 7 days, if patients are dysphagic. Oral hygiene protocols may include antibacterial mouth rinse, systematic oral care, and decontamination gel to decrease the risk of pneumonia .

For deep vein thrombosis prophylaxis, intermittent pneumatic compression, in addition to the aspirin that a patient is on is reasonable, and the benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin or low-molecular-weight heparin) in immobile patients with AIS is not well established.

The bottom line

Early management of stroke involves first determining whether someone is a candidate for reperfusion therapy with alteplase or thrombectomy and then, if not, admitting them to a monitored setting to screen for atrial fibrillation and evaluation for carotid stenosis. Patients should be evaluated for both depression and swallowing function, and there should be initiation of deep vein thrombosis prevention, appropriate management of elevated blood pressures, anti-platelet therapy, and statin therapy as well as plans for rehabilitation services.

Reference

Powers WJ et al. on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Callahan is an attending physician and preceptor in the family medicine residency program at Abington Jefferson Health.

Significant changes have occurred in the updated American Heart Association Stroke Council’s recommendations for early management of acute ischemic stroke (AIS). Conceptually, early management can be separated into initial triage and decisions about intervention to restore blood flow with thrombolysis or mechanical thrombectomy. If reperfusion therapy is not appropriate, then the focus is on management to minimize further damage from the stroke, decrease the likelihood of recurrence, and lessen secondary problems related to the stroke.

All patients with AIS should receive noncontrast CT to determine if there is evidence of a hemorrhagic stroke and, if such evidence exists, than the patient is not a candidate for thrombolysis. Intravenous alteplase should be considered for patients who present within 3 hours of stroke onset and for selected patients presenting between 3-4.5 hours after stroke onset (for more details, see Table 6 in the guidelines). Selected patients with AIS who present within 6-24 hours of last time they were known to be normal and who have large vessel occlusion in the anterior circulation, may be candidates for mechanical thrombectomy in specialized centers. Patients who are not candidates for acute interventions should then be managed according to early stroke management guidelines.

Early stroke management for patients with AIS admitted to medical floors involves attention to blood pressure, glucose, and antiplatelet therapy. For patients with blood pressure lower than 220/120 mm Hg who did not receive IV alteplase or thrombectomy, treatment of hypertension in the first 48-72 hours after an AIS does not change the outcome. It is reasonable when patients have BP greater than or equal to 220/120 mm Hg, to lower blood pressure by 15% during the first 24 hours after onset of stroke. Starting or restarting antihypertensive therapy during hospitalization in patients with blood pressure higher than 140/90 mm Hg who are neurologically stable improves long-term blood pressure control and is considered a reasonable strategy.

For patients with noncardioembolic AIS, the use of antiplatelet agents rather than oral anticoagulation is recommended. Patients should be treated with aspirin 160 mg-325 mg within 24-48 hours of presentation. In patients unsafe or unable to swallow, rectal or nasogastric administration is recommended. In patients with minor stroke, 21 days of dual-antiplatelet therapy (aspirin and clopidogrel) started within 24 hours can decrease stroke recurrence for the first 90 days after a stroke. This recommendation is based on a single study, the CHANCE trial, in a homogeneous population in China, and its generalizability is not known. If a patient had an AIS while already on aspirin, there is some evidence supporting a decreased risk of major cardiovascular events and recurrent stroke in patients switching to an alternative antiplatelet agent or combination antiplatelet therapy. Because of methodologic issues in the those studies, the guideline concludes that, for those already on aspirin, it is of unclear benefit to increase the dose of aspirin, switch to a different antiplatelet agent, or add a second antiplatelet agent. Switching to warfarin is not beneficial for secondary stroke prevention. High-dose statin therapy should be initiated. For patients with AIS in the setting of atrial fibrillation, oral anticoagulation can be started within 4-14 days after the stroke. One study showed that anticoagulation should not be started before 4 days after the stroke, with a hazard ratio of 0.53 for starting anticoagulation at 4-14 days, compared with less than 4 days.

Hyperglycemia should be controlled to a range of 140-180 mg/dL, because higher values are associated with worse outcomes. Oxygen should be used if needed to maintain oxygen saturation greater than 94%. High-intensity statin therapy should be used, and smoking cessation is strongly encouraged for those who use tobacco, with avoidance of secondhand smoke whenever possible.

Patients should be screened for dysphagia before taking anything per oral, including medications. A nasogastric tube may be considered within the first 7 days, if patients are dysphagic. Oral hygiene protocols may include antibacterial mouth rinse, systematic oral care, and decontamination gel to decrease the risk of pneumonia .

For deep vein thrombosis prophylaxis, intermittent pneumatic compression, in addition to the aspirin that a patient is on is reasonable, and the benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin or low-molecular-weight heparin) in immobile patients with AIS is not well established.

The bottom line

Early management of stroke involves first determining whether someone is a candidate for reperfusion therapy with alteplase or thrombectomy and then, if not, admitting them to a monitored setting to screen for atrial fibrillation and evaluation for carotid stenosis. Patients should be evaluated for both depression and swallowing function, and there should be initiation of deep vein thrombosis prevention, appropriate management of elevated blood pressures, anti-platelet therapy, and statin therapy as well as plans for rehabilitation services.

Reference

Powers WJ et al. on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Callahan is an attending physician and preceptor in the family medicine residency program at Abington Jefferson Health.

Significant changes have occurred in the updated American Heart Association Stroke Council’s recommendations for early management of acute ischemic stroke (AIS). Conceptually, early management can be separated into initial triage and decisions about intervention to restore blood flow with thrombolysis or mechanical thrombectomy. If reperfusion therapy is not appropriate, then the focus is on management to minimize further damage from the stroke, decrease the likelihood of recurrence, and lessen secondary problems related to the stroke.

All patients with AIS should receive noncontrast CT to determine if there is evidence of a hemorrhagic stroke and, if such evidence exists, than the patient is not a candidate for thrombolysis. Intravenous alteplase should be considered for patients who present within 3 hours of stroke onset and for selected patients presenting between 3-4.5 hours after stroke onset (for more details, see Table 6 in the guidelines). Selected patients with AIS who present within 6-24 hours of last time they were known to be normal and who have large vessel occlusion in the anterior circulation, may be candidates for mechanical thrombectomy in specialized centers. Patients who are not candidates for acute interventions should then be managed according to early stroke management guidelines.

Early stroke management for patients with AIS admitted to medical floors involves attention to blood pressure, glucose, and antiplatelet therapy. For patients with blood pressure lower than 220/120 mm Hg who did not receive IV alteplase or thrombectomy, treatment of hypertension in the first 48-72 hours after an AIS does not change the outcome. It is reasonable when patients have BP greater than or equal to 220/120 mm Hg, to lower blood pressure by 15% during the first 24 hours after onset of stroke. Starting or restarting antihypertensive therapy during hospitalization in patients with blood pressure higher than 140/90 mm Hg who are neurologically stable improves long-term blood pressure control and is considered a reasonable strategy.

For patients with noncardioembolic AIS, the use of antiplatelet agents rather than oral anticoagulation is recommended. Patients should be treated with aspirin 160 mg-325 mg within 24-48 hours of presentation. In patients unsafe or unable to swallow, rectal or nasogastric administration is recommended. In patients with minor stroke, 21 days of dual-antiplatelet therapy (aspirin and clopidogrel) started within 24 hours can decrease stroke recurrence for the first 90 days after a stroke. This recommendation is based on a single study, the CHANCE trial, in a homogeneous population in China, and its generalizability is not known. If a patient had an AIS while already on aspirin, there is some evidence supporting a decreased risk of major cardiovascular events and recurrent stroke in patients switching to an alternative antiplatelet agent or combination antiplatelet therapy. Because of methodologic issues in the those studies, the guideline concludes that, for those already on aspirin, it is of unclear benefit to increase the dose of aspirin, switch to a different antiplatelet agent, or add a second antiplatelet agent. Switching to warfarin is not beneficial for secondary stroke prevention. High-dose statin therapy should be initiated. For patients with AIS in the setting of atrial fibrillation, oral anticoagulation can be started within 4-14 days after the stroke. One study showed that anticoagulation should not be started before 4 days after the stroke, with a hazard ratio of 0.53 for starting anticoagulation at 4-14 days, compared with less than 4 days.

Hyperglycemia should be controlled to a range of 140-180 mg/dL, because higher values are associated with worse outcomes. Oxygen should be used if needed to maintain oxygen saturation greater than 94%. High-intensity statin therapy should be used, and smoking cessation is strongly encouraged for those who use tobacco, with avoidance of secondhand smoke whenever possible.

Patients should be screened for dysphagia before taking anything per oral, including medications. A nasogastric tube may be considered within the first 7 days, if patients are dysphagic. Oral hygiene protocols may include antibacterial mouth rinse, systematic oral care, and decontamination gel to decrease the risk of pneumonia .

For deep vein thrombosis prophylaxis, intermittent pneumatic compression, in addition to the aspirin that a patient is on is reasonable, and the benefit of prophylactic-dose subcutaneous heparin (unfractionated heparin or low-molecular-weight heparin) in immobile patients with AIS is not well established.

The bottom line

Early management of stroke involves first determining whether someone is a candidate for reperfusion therapy with alteplase or thrombectomy and then, if not, admitting them to a monitored setting to screen for atrial fibrillation and evaluation for carotid stenosis. Patients should be evaluated for both depression and swallowing function, and there should be initiation of deep vein thrombosis prevention, appropriate management of elevated blood pressures, anti-platelet therapy, and statin therapy as well as plans for rehabilitation services.

Reference

Powers WJ et al. on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110.

Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Callahan is an attending physician and preceptor in the family medicine residency program at Abington Jefferson Health.

The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.¹ This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).

Importance

Wavebreakmedia/Thinkstock

Screening methods

The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).

The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.

In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
 

Effectiveness of intervention or treatment

Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.

Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.

Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.

Association between spinal curvature severity and adult health outcomes

The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.

Recommendation of others

The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.²

Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
 

The Bottom Line

Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.

References

1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.

2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
 

The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.¹ This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).

Importance

Wavebreakmedia/Thinkstock

Screening methods

The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).

The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.

In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
 

Effectiveness of intervention or treatment

Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.

Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.

Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.

Association between spinal curvature severity and adult health outcomes

The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.

Recommendation of others

The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.²

Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
 

The Bottom Line

Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.

References

1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.

2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
 

The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.¹ This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).

Importance

Wavebreakmedia/Thinkstock

Screening methods

The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).

The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.

In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
 

Effectiveness of intervention or treatment

Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.

Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.

Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.

Association between spinal curvature severity and adult health outcomes

The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.

Recommendation of others

The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.²

Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
 

The Bottom Line

Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.

References

1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.

2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
 

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.

Measurement

While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.

Kidney injury

Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.

Bleeding

Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.

Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
 

Overdose

Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.

Intracranial hemorrhage

Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.

Ischemic stroke

Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.

The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
 

Procedures and surgeries

Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.

Spinal or epidural anesthesia

Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.

The bottom line

NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.

Reference

Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477

While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.

Diagnostic tests for LTBI

The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.

Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.

Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.

Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.

Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.

In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
 

Bottom line

Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

Reference

Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.

While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.

Diagnostic tests for LTBI

The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.

Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.

Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.

Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.

Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.

In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
 

Bottom line

Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

Reference

Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.

While cases of active tuberculosis are relatively rare in the United States, TB is a major cause of morbidity and mortality worldwide. In the United States, there are an estimated 11 million individuals who have latent TB infection (LTBI). Without prophylactic treatment, somewhere between 4%-6% of individuals with LTBI will develop active disease during their lifetimes; roughly half of these cases will occur within a few years of the initial infection. Treatment of LTBI reduces – but does not eliminate – the risk for active disease, decreasing the consequences of active disease for the patient and the risk of transmitting infection to others.

Diagnostic tests for LTBI

The tuberculin skin test (TST) has been the standard method of diagnosing LTBI. It involves measuring induration caused by a delayed-type hypersensitivity reaction to Mycobacterium tuberculosis (Mtb) 2 or 3 days after injecting the reagent into the skin. The TST can result in false positives when detecting antibodies to BCG and nontuberculous mycobacteria, and false negatives when the patient does not demonstrate a robust immune response. A newer testing method is the Interferon Gamma Release Assay (IGRA), which involves phlebotomy, followed by a series of laboratory procedures that measure IFN-gamma release by T cells that have been sensitized to Mtb. The sensitivity of IGRA is similar to the TST, but it has better specificity; it is much less likely to react to antigens from BCG or nontuberculous mycobacteria. As detailed below, this guideline suggests a significantly more prominent role for IGRA, compared with previous recommendations.

Recommendation 1. Perform an IGRA, rather than a TST, in individuals 5 years or older who meet the following criteria: 1) are likely to be infected with Mtb; 2) have a low or intermediate risk of disease progression; 3) in whom it has been decided that testing for LTBI is warranted. A TST is an acceptable alternative, particularly if an IGRA is not available, is too costly, or is too burdensome. If an individual either has a history of BCG vaccination or is unlikely to return to have their TST read, then it is strongly recommended to use the IGRA as the test of choice.

Recommendation 2. There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to active disease, and in whom it has been determined that diagnostic testing for LTBI infection is warranted; either test would be acceptable. In very high-risk patients, consider dual testing, with a positive result from either test (TST or IGRA) being considered positive.

Recommendation 3. Guidelines do not recommend testing for persons at low risk for Mtb infection. However, the authors recognize that testing in such persons may nevertheless be mandated in certain situations (for example in some school or child care settings). In these cases, the authors recommend performing an IGRA instead of a TST, to minimize the chance of a false-positive result, although a TST is an acceptable alternative. Furthermore, if the initial test is positive, they suggest performing a confirmatory test (either an IGRA or TST) and considering the person infected only if both tests are positive.

Recommendation 4. The authors suggest performing a TST rather than an IGRA in healthy children less than 5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted. This recommendation reflects the limited body of evidence regarding IGRA testing in young children and the apparent decreased sensitivity (i.e. more false negatives) in this population, compared with TST use.

In the area of serial testing for TB infection, often done in health care and institutional settings, the guideline points out areas of uncertainty with IGRA testing. Specifically, the IGRA test is subject to variability in readings and boosting with antigen exposure that can complicate interpretation of apparent conversion on repeat testing. One longitudinal study showed conversion rates with IGRA to be six to nine times higher than that seen for the TST, and those conversions were thought to represent false positive tests. The guideline concludes that, “There is insufficient information available to guide the establishment of definitive criteria for the conversion.” The committee thought that a positive test in a low-risk individual was likely to be a false-positive result and recommended repeat testing. Because of the possibility of boosting with antigen exposure in situations where dual testing is anticipated, it may be preferable to obtain a specimen for IGRA prior to, or concurrently with TST placement.
 

Bottom line

Current guidelines suggest a more prominent role for IGRA in testing for LTBI, particularly when the likelihood of exposure is low and in situations where a person may have received BCG vaccination, or would be unlikely to return for TST reading.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Clark is associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

Reference

Lewisohn DM et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Inf Dis. 2017;64(2):111-5.

Syncope is characterized by sudden transient loss of consciousness due to cerebral hypoperfusion and is typically associated with an inability to maintain postural tone. There are many different causes and clinical presentations of syncope and the incidence varies depending on the population. Estimated lifetime prevalence rates are as high as 41% for a single episode of syncope, with recurrent syncope occurring in 13.5% of the general population. Incidence follows a trimodal distribution with peaks at age 20, 60, and 80 years for both men and women. The National Hospital Ambulatory Medical Care Survey reported 6.7 million episodes of syncope in the emergency department, which is where most patients with syncope initially present. However, patients may also present to the primary care outpatient setting, and providers should be equipped for initial evaluation and management.

Previous and current treatment guidelines

Although there have been general reviews published by general and specialty societies, there were no comprehensive guidelines on the evaluation and management of syncope until recently. The 2017 guideline from the American College of Cardiology, American Heart Association, and Heart Rhythm Society is intended to provide guidance on evaluation and management of syncope, specifically in the context of different clinical settings, specific causes, or selected circumstances.¹

What primary care providers should know

A detailed history and physical exam should be performed in all patients with syncope. Useful details include the setting in which syncope occurs, prodromal symptoms, witness reports, postevent symptoms, comorbidities, medication use, past medical history, and family history. The physical exam should include orthostatic vital signs, cardiac exam, neurologic exam, and any other relevant systems. A resting 12-lead ECG in the initial evaluation is recommended to detect underlying arrhythmia or structural heart disease (Class I recommendation – strong).

There are many different causes of syncope (see Table 1). Vasovagal syncope, a form of reflex syncope mediated by the vasovagal reflex, is the most common cause of syncope and a frequent reason for emergency department visits. There is often a prodrome of diaphoresis, warmth, nausea, and/or pallor, often followed by fatigue. The diagnosis can be made by the history, physical exam, and eyewitness observation.

Special populations

There are specific considerations for certain populations. In the pediatric population, the vast majority of syncopal episodes are reflex syncope but breath-holding spells should also be considered. In the geriatric population, particularly individuals older than 75 years, the incidence of syncope is high, the differential diagnosis is broad, and the diagnosis may be imprecise given amnesia, falls, lack of witnesses, and polypharmacy. In this group, morbidity is high because of multimorbidity and frailty. A careful history and physical exam with orthostatic vital signs is important, as is a multidisciplinary approach with geriatric consultation when needed.

Summary

Syncope is a common clinical syndrome often presenting to the emergency department or primary care setting. There are many causes, the most common being vasovagal syncope. In the initial evaluation, providers should perform a detailed history and physical exam, check orthostatic signs and perform a 12-lead ECG. Patients can be evaluated and managed safely in the outpatient setting in the absence of risk factors. Routine comprehensive laboratory testing and cardiac imaging are often not needed. For patients with defined risk factors, a more detailed evaluation in the hospital is recommended.

Dr. Li is a second-year resident in the family medicine residency program in the department of family and community medicine at the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the departments of family and community medicine and physiology at the Sidney Kimmel Medical College. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. Shen W, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope. Circulation. 2017 Aug 1;136(5):e60-e122. doi: 10.1161/CIR.0000000000000499. Epub 2017 Mar 9.

2. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-85.

Syncope is characterized by sudden transient loss of consciousness due to cerebral hypoperfusion and is typically associated with an inability to maintain postural tone. There are many different causes and clinical presentations of syncope and the incidence varies depending on the population. Estimated lifetime prevalence rates are as high as 41% for a single episode of syncope, with recurrent syncope occurring in 13.5% of the general population. Incidence follows a trimodal distribution with peaks at age 20, 60, and 80 years for both men and women. The National Hospital Ambulatory Medical Care Survey reported 6.7 million episodes of syncope in the emergency department, which is where most patients with syncope initially present. However, patients may also present to the primary care outpatient setting, and providers should be equipped for initial evaluation and management.

Previous and current treatment guidelines

Although there have been general reviews published by general and specialty societies, there were no comprehensive guidelines on the evaluation and management of syncope until recently. The 2017 guideline from the American College of Cardiology, American Heart Association, and Heart Rhythm Society is intended to provide guidance on evaluation and management of syncope, specifically in the context of different clinical settings, specific causes, or selected circumstances.¹

What primary care providers should know

A detailed history and physical exam should be performed in all patients with syncope. Useful details include the setting in which syncope occurs, prodromal symptoms, witness reports, postevent symptoms, comorbidities, medication use, past medical history, and family history. The physical exam should include orthostatic vital signs, cardiac exam, neurologic exam, and any other relevant systems. A resting 12-lead ECG in the initial evaluation is recommended to detect underlying arrhythmia or structural heart disease (Class I recommendation – strong).

There are many different causes of syncope (see Table 1). Vasovagal syncope, a form of reflex syncope mediated by the vasovagal reflex, is the most common cause of syncope and a frequent reason for emergency department visits. There is often a prodrome of diaphoresis, warmth, nausea, and/or pallor, often followed by fatigue. The diagnosis can be made by the history, physical exam, and eyewitness observation.

Special populations

There are specific considerations for certain populations. In the pediatric population, the vast majority of syncopal episodes are reflex syncope but breath-holding spells should also be considered. In the geriatric population, particularly individuals older than 75 years, the incidence of syncope is high, the differential diagnosis is broad, and the diagnosis may be imprecise given amnesia, falls, lack of witnesses, and polypharmacy. In this group, morbidity is high because of multimorbidity and frailty. A careful history and physical exam with orthostatic vital signs is important, as is a multidisciplinary approach with geriatric consultation when needed.

Summary

Syncope is a common clinical syndrome often presenting to the emergency department or primary care setting. There are many causes, the most common being vasovagal syncope. In the initial evaluation, providers should perform a detailed history and physical exam, check orthostatic signs and perform a 12-lead ECG. Patients can be evaluated and managed safely in the outpatient setting in the absence of risk factors. Routine comprehensive laboratory testing and cardiac imaging are often not needed. For patients with defined risk factors, a more detailed evaluation in the hospital is recommended.

Dr. Li is a second-year resident in the family medicine residency program in the department of family and community medicine at the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the departments of family and community medicine and physiology at the Sidney Kimmel Medical College. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. Shen W, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope. Circulation. 2017 Aug 1;136(5):e60-e122. doi: 10.1161/CIR.0000000000000499. Epub 2017 Mar 9.

2. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-85.

Syncope is characterized by sudden transient loss of consciousness due to cerebral hypoperfusion and is typically associated with an inability to maintain postural tone. There are many different causes and clinical presentations of syncope and the incidence varies depending on the population. Estimated lifetime prevalence rates are as high as 41% for a single episode of syncope, with recurrent syncope occurring in 13.5% of the general population. Incidence follows a trimodal distribution with peaks at age 20, 60, and 80 years for both men and women. The National Hospital Ambulatory Medical Care Survey reported 6.7 million episodes of syncope in the emergency department, which is where most patients with syncope initially present. However, patients may also present to the primary care outpatient setting, and providers should be equipped for initial evaluation and management.

Previous and current treatment guidelines

Although there have been general reviews published by general and specialty societies, there were no comprehensive guidelines on the evaluation and management of syncope until recently. The 2017 guideline from the American College of Cardiology, American Heart Association, and Heart Rhythm Society is intended to provide guidance on evaluation and management of syncope, specifically in the context of different clinical settings, specific causes, or selected circumstances.¹

What primary care providers should know

A detailed history and physical exam should be performed in all patients with syncope. Useful details include the setting in which syncope occurs, prodromal symptoms, witness reports, postevent symptoms, comorbidities, medication use, past medical history, and family history. The physical exam should include orthostatic vital signs, cardiac exam, neurologic exam, and any other relevant systems. A resting 12-lead ECG in the initial evaluation is recommended to detect underlying arrhythmia or structural heart disease (Class I recommendation – strong).

There are many different causes of syncope (see Table 1). Vasovagal syncope, a form of reflex syncope mediated by the vasovagal reflex, is the most common cause of syncope and a frequent reason for emergency department visits. There is often a prodrome of diaphoresis, warmth, nausea, and/or pallor, often followed by fatigue. The diagnosis can be made by the history, physical exam, and eyewitness observation.

Special populations

There are specific considerations for certain populations. In the pediatric population, the vast majority of syncopal episodes are reflex syncope but breath-holding spells should also be considered. In the geriatric population, particularly individuals older than 75 years, the incidence of syncope is high, the differential diagnosis is broad, and the diagnosis may be imprecise given amnesia, falls, lack of witnesses, and polypharmacy. In this group, morbidity is high because of multimorbidity and frailty. A careful history and physical exam with orthostatic vital signs is important, as is a multidisciplinary approach with geriatric consultation when needed.

Summary

Syncope is a common clinical syndrome often presenting to the emergency department or primary care setting. There are many causes, the most common being vasovagal syncope. In the initial evaluation, providers should perform a detailed history and physical exam, check orthostatic signs and perform a 12-lead ECG. Patients can be evaluated and managed safely in the outpatient setting in the absence of risk factors. Routine comprehensive laboratory testing and cardiac imaging are often not needed. For patients with defined risk factors, a more detailed evaluation in the hospital is recommended.

Dr. Li is a second-year resident in the family medicine residency program in the department of family and community medicine at the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the departments of family and community medicine and physiology at the Sidney Kimmel Medical College. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. Shen W, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope. Circulation. 2017 Aug 1;136(5):e60-e122. doi: 10.1161/CIR.0000000000000499. Epub 2017 Mar 9.

2. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12):878-85.