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In This Edition
Literature at a Glance
A guide to this month’s studies
- Effect of early follow-up on readmission rates
- Heart rate control and outcomes in atrial fibrillation
- Pneumococcal vaccine to prevent stroke and MI
- Long-term outcomes of endovascular repair of AAA
- Insurance and outcomes in myocardial infarction
- Risk of gastrointestinal bleeding and cardiovascular outcomes with concurrent PPI and clopidogrel use
- CT in patients with suspected coronary artery disease
Reduced 30-Day Readmission Rate for Patients Discharged from Hospitals with Higher Rates of Early Follow-Up
Clinical question: Is early follow-up after discharge for heart failure associated with a reduction in readmission rates?
Background: Readmission for heart failure is very frequent and often unplanned. Early follow-up visits after discharge have been hypothesized to reduce readmissions but have been undefined.
Study design: Retrospective cohort study.
Setting: Patients with Medicare inpatient claims data linked to the OPTIMIZE-HF and GWTG-HF registries.
Synopsis: The study included 30,136 patients >65 years old with the principal discharge diagnosis of heart failure from 2003 to 2006. Hospitals were stratified into quartiles based upon the median arrival rate to “early” (within one week after discharge) follow-up appointments. Ranges of arrival rates to these appointments ranged from Quartile 1 (Q1) (<32.4% of patients) to Q4 (>44.5%). Readmission rates were highest in the lowest quartile of “early” follow-up (Q1: 23.3%; Q2: 20.5%; Q3: 20.5%; Q4: 20.5%, P<0.001). No mortality difference was seen.
The study also examined whether the physician following the patient after discharge impacted the readmission rate for these same quartiles, comparing cardiologists to generalists and comparing the same physician at discharge and follow-up (defined as “continuity”) versus different physicians. Follow-up with continuity or a cardiologist did not reduce readmissions.
Interestingly, nearly all markers of quality were best in Q1 and Q2 hospitals, which had the lowest arrival rates to appointments, which might reflect patient-centered rather than hospital-centered issues.
Bottom line: Hospitals with low “early” follow-up appointment rates after discharge have a higher readmission rate, although causality is not established.
Citation: Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303 (17):1716-1722.
Strict Heart Rate Control Is Not Necessary in Management of Chronic Atrial Fibrillation
Clinical question: Is lenient heart rate control inferior to strict heart rate control in preventing cardiovascular events in patients with chronic atrial fibrillation?
Background: Guidelines generally call for the use of medications to achieve strict heart rate control in the management of chronic atrial fibrillation, but the optimal level of heart rate control necessary to avoid cardiovascular events remains uncertain.
Study design: Prospectively randomized, noninferiority trial.
Setting: Thirty-three medical centers in the Netherlands.
Synopsis: The study looked at 614 patients with permanent atrial fibrillation; 311 patients were randomized to lenient control and 303 to strict control. Calcium channel blockers, beta-blockers, or digoxin were dose-adjusted to control heart rate below 110 beats per minute (bpm) in the lenient control group versus 80 bpm in the strict control group.
Thirty-eight patients (12.9%) in the lenient control group and 43 (14.9%) in the strict control group reached the primary composite outcome of significant cardiovascular events (death, heart failure, stroke, embolism, major bleeding, major arrhythmia, need for pacemaker, or severe drug adverse event). Although no statistical difference in the frequency of these events between groups was detected, the study was dramatically underpowered due to unanticipated low event rates.
Bottom line: Although the lenient control group had far fewer outpatient visits and a trend toward improved outcomes, no definite conclusion regarding the management of permanent atrial fibrillation can be drawn from this underpowered noninferiority trial.
Citation: Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362(15):1363-1373.
Pneumococcal Vaccine Does Not Reduce the Risk of Stroke or Myocardial Infarction
Clinical question: Does pneumococcal vaccination reduce the risk of acute myocardial infarction (MI) and stroke?
Background: Studies have demonstrated that influenza vaccination reduces the risk of cardiac and cerebrovascular events. A single study has shown similar outcomes for the pneumococcal vaccination, although the study was limited by confounders and selection bias.
Study design: Retrospective cohort.
Setting: Large HMO in California.
Synopsis: More than 84,000 men participating in the California Men’s Health Study (CMHS) and enrolled in the Kaiser Permanente health plan were categorized as unvaccinated or vaccinated with the pneumococcal vaccine. Vaccinated patients had 10.73 first MIs and 5.30 strokes per 1,000 person-years, compared with unvaccinated patients who incurred 6.07 MIs and 1.90 strokes per 1,000 unvaccinated person-years based on ICD-9 codes.
Even with propensity scoring to minimize selection bias, no clear evidence of benefit was observed. One significant limitation is that 80% of the unvaccinated patients were younger than 60 years old, whereas 74% of the vaccinated patients were 60 or older; this might represent selection bias that cannot be overcome with propensity scoring.
Bottom line: In a population of men older than age 45, pneumococcal vaccination does not appear to reduce the risk of acute MI or stroke.
Citation: Tseng HF, Slezak JM, Quinn VP, et al. Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men. JAMA. 2010;303(17):1699-1706.
No Durable Mortality Benefit from Endovascular Repair of Enlarged Abdominal Aortic Aneurysm
Clinical question: What is the cost and mortality benefit of endovascular versus open repair of abdominal aneurysms?
Background: Previous studies demonstrated a 30-day mortality benefit using endovascular repair over open surgical repair of large abdominal aortic aneurysms. Limited longer-term data are available assessing the durability of these findings.
Study design: Randomized controlled trial.
Setting: Thirty-seven hospitals in the United Kingdom.
Synopsis: Researchers looked at 1,252 patients who were at least 60 years old with a large abdominal aortic aneurysm (>5.5 cm) on CT scan. The patients were randomized to open versus endovascular repair and followed for a median of six years postoperatively. An early, postoperative, all-cause mortality benefit was observed for endovascular repair (1.8%) compared with open repair (4.3%), but no benefit was seen after six months of follow-up, driven by secondary aneurysm ruptures with endovascular grafts. Graft-related complications in all time periods were higher in the endovascular repair group, highest from 0 to 6 months (nearly 50% of patients), and were associated with an increased cost.
Bottom line: Immediate postoperative mortality benefit of endovascular repair is not sustained for abdominal aortic aneurysm beyond six months postoperatively.
Citation: The United Kingdom EVAR trial investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010:362(20):1863-1870.
Financial Constraints Delay Presentation in Patients Suffering from Acute Myocardial Infarction
Clinical question: Does being underinsured or uninsured delay individuals from seeking treatment for emergency medical care?
Background: The number of underinsured or uninsured Americans is growing. Studies have shown that patients with financial concerns avoid routine preventive and chronic medical care; however, similar avoidance has not been defined clearly for patients seeking emergent care.
Study design: Prospective cohort study.
Setting: Twenty-four urban hospitals in the U.S. included in a multisite, acute myocardial infarction (AMI) registry.
Synopsis: Of the 3,721 patients enrolled in the AMI registry, 61.7% of the cohort was insured and without financial concerns that prevented them from seeking care. These patients were less likely to have delays in care related to AMI compared with patients who were insured with financial concerns (18.5% of the cohort; OR 1.22; 95% confidence interval [CI], 1.06-1.40) or uninsured (19.8%; OR 1.30; 95% CI, 1.12-1.51) in all time frames after symptom onset. Patients were less likely to undergo PCI or thrombolysis if the delay to presentation was more than six hours.
After adjustment for confounding factors, the authors concluded that uninsured and underinsured patients were likely to delay presentation to the hospital. Despite these findings, alternative etiologies for delays in care are likely to be more significant, as insurance considerations only account for an 8% difference between the well-insured group (39.3% delayed seeking care >6 hours) and the uninsured group (48.6%). These etiologies are ill-defined.
Bottom line: Underinsured or uninsured patients have a small but significant delay in seeking treatment for AMI due to financial concerns.
Citation: Smolderen KG, Spertus JA, Nallamothu BK, et al. Health care insurance, financial concerns in accessing care, and delays to hospital presentation in acute myocardial infarction. JAMA. 2010;303 (14):1392-1400.
Concurrent Use of PPIs and Clopidogrel Decrease Hospitalizations for Gastroduodenal Bleeding without Significant Increase in Adverse Cardiovascular Events
Clinical question: Does concomitant use of proton-pump inhibitors (PPIs) and clopidogrel affect the risks of hospitalizations for gastroduodenal bleeding and serious cardiovascular events?
Background: PPIs commonly are prescribed with clopidogrel to reduce the risk of serious gastroduodenal bleeding. Recent observational studies suggest that concurrent PPI and clopidogrel administration might increase the risk of cardiovascular events compared with clopidogrel alone.
Study design: Retrospective cohort.
Setting: Tennessee Medicaid program.
Synopsis: Researchers identified 20,596 patients hospitalized for acute MI, revascularization, or unstable angina, and prescribed clopidogrel. Of this cohort, 7,593 were initial concurrent PPI users—62% used pantoprazole and 9% used omeprazole. Hospitalizations for gastroduodenal bleeding were reduced by 50% (HR 0.50 [95% CI, 0.39-0.65]) in concurrent users of PPIs and clopidogrel, compared with nonusers of PPIs.
Concurrent use was not associated with a statistically significant increase in serious cardiovascular diseases (HR, 0.99 [95% CI, 0.82-1.19]), defined as acute MI, sudden cardiac death, nonfatal or fatal stroke, or other cardiovascular deaths.
Subgroup analyses of individual PPIs and patients undergoing percutaneous coronary interventions also showed no increased risk of serious cardiovascular events. This study could differ from previous observational studies because far fewer patients were on omeprazole, the most potent inhibitor of clopidogrel.
Bottom line: In patients treated with clopidogrel, PPI users had 50% fewer hospitalizations for gastroduodenal bleeding compared with nonusers. Concurrent use of clopidogrel and PPIs, most of which was pantoprazole, was not associated with a significant increase in serious cardiovascular events.
Citation: Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors. Ann Intern Med. 2010;152(6):337-345.
CTCA a Promising, Noninvasive Option in Evaluating Patients with Suspected Coronary Artery Disease
Clinical question: How does computed tomography coronary angiography (CTCA) compare to noninvasive stress testing for diagnosing coronary artery disease (CAD)?
Background: CTCA is a newer, noninvasive test that has a high diagnostic accuracy for CAD, but its clinical role in the evaluation of patients with chest symptoms is unclear.
Study design: Observational study.
Setting: Single academic center in the Netherlands.
Synopsis: Five hundred seventeen eligible patients were evaluated with stress testing and CTCA. The patients were classified as having a low (<20%), intermediate (20%-80%), or high (>80%) pretest probability of CAD based on the Duke clinical score. Using coronary angiography as the gold standard, stress-testing was found to be less accurate than CTCA in all of the patient groups. In patients with low and intermediate pretest probabilities, a negative CTCA had a post-test probability of 0% and 1%, respectively. On the other hand, patients with an intermediate pretest probability and a positive CTCA had a post-test probability of 94% (CI, 89%-97%). In patients with an initial high pretest probability, stress-testing and CTCA confirmed disease in most cases.
The results of this study suggest that CTCA is particularly useful in evaluating patients with an intermediate pretest probability.
Patients were ineligible in this study if they had acute coronary syndromes, previous coronary stent placement, coronary artery bypass surgery, or myocardial infarction. It is important to note that because anatomic lesions seen on imaging (CTCA and coronary angiography) are not always functionally significant, CTCA might have seemed more accurate and clinically useful than it actually is. The investigators also acknowledge that further studies are necessary before CTCA can be accepted as a first-line diagnostic test.
Bottom line: In patients with an intermediate pretest probability of CAD, a negative CTCA is valuable in excluding coronary artery disease, thereby reducing the need for invasive coronary angiography in this group.
Citation: Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med. 2010;152(10):630-639. TH
PEDIATRIC HM LITerature
Neonatal Nonhemolytic Hyperbilirubinemia Not Associated with Long-Term Cognitive or Neuropsychiatric Disability
Clinical question: Is exposure to neonatal nonhemolytic hyperbilirubinemia associated with negative long-term cognitive effects?
Background: Guidelines for the treatment of neonatal hyperbilirubinemia focus on the prevention of rare but potentially devastating consequences: bilirubin encephalopathy and subsequent kernicterus. Small studies have raised concerns regarding the potential for long-term cognitive disability in infants exposed to severe hyperbilirubinemia without kernicterus. This association primarily has been noted in patients with severe hemolytic hyperbilirubinemia; the relationship in nonhemolytic cases is less clear.
Study design: Retrospective, population-based cohort study.
Setting: Fifth Military Conscription District of Denmark.
Synopsis: All 18-year-old male conscripts born from 1977 to 1983 had data extracted from a national discharge registry with respect to maximum total serum bilirubin (TSB-max) and other clinical details. Infants born <35 weeks or of multiple gestation, age >14 days at TSB-max, or with hemolytic disease were excluded. TSB-max was analyzed as a categorical and dichotomous variable. Data were then compared to a validated Danish intelligence test administered at military draft conscription and the presence of neuropsychiatric diagnoses.
Of those examined, 463 men exceeded the cutoff for TSB-max, compared with 12,718 controls. There were no significant differences between groups with respect to the presence of neuropsychiatric diagnoses or cognitive performance.
This study benefits from its population-based design and use of an inclusive national database. However, cognitive performance is notoriously difficult to study, owing to the numerous potential confounders, many of which could not be ascertained retrospectively from the registry. Additional limitations were that the Danish thresholds for phototherapy and exchange transfusion were 240 μmol/L and 340 μmol/L (or approximately 14 mg/dL and 20 mg/dL), respectively, and only 25 newborns were exposed to levels greater than 340 μmol/L.
Although no dose response association was noted between 240 μmol/L and 340 μmol/L, no conclusions may be drawn regarding significantly higher levels.
Bottom line: Neonatal nonhemolytic hyperbilirubinemia requiring phototherapy is unlikely to be associated with long-term cognitive or neuropsychiatric disability.
Citation: Ebbesen F, Ehrenstein V, Traeger M, Nielsen GL. Neonatal non-hemolytic hyperbilirubinemia: a prevalence study of adult neuropsychiatric disability and cognitive function in 463 male Danish conscripts. Arch Dis Child. 2010;95(8):583-587.
In This Edition
Literature at a Glance
A guide to this month’s studies
- Effect of early follow-up on readmission rates
- Heart rate control and outcomes in atrial fibrillation
- Pneumococcal vaccine to prevent stroke and MI
- Long-term outcomes of endovascular repair of AAA
- Insurance and outcomes in myocardial infarction
- Risk of gastrointestinal bleeding and cardiovascular outcomes with concurrent PPI and clopidogrel use
- CT in patients with suspected coronary artery disease
Reduced 30-Day Readmission Rate for Patients Discharged from Hospitals with Higher Rates of Early Follow-Up
Clinical question: Is early follow-up after discharge for heart failure associated with a reduction in readmission rates?
Background: Readmission for heart failure is very frequent and often unplanned. Early follow-up visits after discharge have been hypothesized to reduce readmissions but have been undefined.
Study design: Retrospective cohort study.
Setting: Patients with Medicare inpatient claims data linked to the OPTIMIZE-HF and GWTG-HF registries.
Synopsis: The study included 30,136 patients >65 years old with the principal discharge diagnosis of heart failure from 2003 to 2006. Hospitals were stratified into quartiles based upon the median arrival rate to “early” (within one week after discharge) follow-up appointments. Ranges of arrival rates to these appointments ranged from Quartile 1 (Q1) (<32.4% of patients) to Q4 (>44.5%). Readmission rates were highest in the lowest quartile of “early” follow-up (Q1: 23.3%; Q2: 20.5%; Q3: 20.5%; Q4: 20.5%, P<0.001). No mortality difference was seen.
The study also examined whether the physician following the patient after discharge impacted the readmission rate for these same quartiles, comparing cardiologists to generalists and comparing the same physician at discharge and follow-up (defined as “continuity”) versus different physicians. Follow-up with continuity or a cardiologist did not reduce readmissions.
Interestingly, nearly all markers of quality were best in Q1 and Q2 hospitals, which had the lowest arrival rates to appointments, which might reflect patient-centered rather than hospital-centered issues.
Bottom line: Hospitals with low “early” follow-up appointment rates after discharge have a higher readmission rate, although causality is not established.
Citation: Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303 (17):1716-1722.
Strict Heart Rate Control Is Not Necessary in Management of Chronic Atrial Fibrillation
Clinical question: Is lenient heart rate control inferior to strict heart rate control in preventing cardiovascular events in patients with chronic atrial fibrillation?
Background: Guidelines generally call for the use of medications to achieve strict heart rate control in the management of chronic atrial fibrillation, but the optimal level of heart rate control necessary to avoid cardiovascular events remains uncertain.
Study design: Prospectively randomized, noninferiority trial.
Setting: Thirty-three medical centers in the Netherlands.
Synopsis: The study looked at 614 patients with permanent atrial fibrillation; 311 patients were randomized to lenient control and 303 to strict control. Calcium channel blockers, beta-blockers, or digoxin were dose-adjusted to control heart rate below 110 beats per minute (bpm) in the lenient control group versus 80 bpm in the strict control group.
Thirty-eight patients (12.9%) in the lenient control group and 43 (14.9%) in the strict control group reached the primary composite outcome of significant cardiovascular events (death, heart failure, stroke, embolism, major bleeding, major arrhythmia, need for pacemaker, or severe drug adverse event). Although no statistical difference in the frequency of these events between groups was detected, the study was dramatically underpowered due to unanticipated low event rates.
Bottom line: Although the lenient control group had far fewer outpatient visits and a trend toward improved outcomes, no definite conclusion regarding the management of permanent atrial fibrillation can be drawn from this underpowered noninferiority trial.
Citation: Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362(15):1363-1373.
Pneumococcal Vaccine Does Not Reduce the Risk of Stroke or Myocardial Infarction
Clinical question: Does pneumococcal vaccination reduce the risk of acute myocardial infarction (MI) and stroke?
Background: Studies have demonstrated that influenza vaccination reduces the risk of cardiac and cerebrovascular events. A single study has shown similar outcomes for the pneumococcal vaccination, although the study was limited by confounders and selection bias.
Study design: Retrospective cohort.
Setting: Large HMO in California.
Synopsis: More than 84,000 men participating in the California Men’s Health Study (CMHS) and enrolled in the Kaiser Permanente health plan were categorized as unvaccinated or vaccinated with the pneumococcal vaccine. Vaccinated patients had 10.73 first MIs and 5.30 strokes per 1,000 person-years, compared with unvaccinated patients who incurred 6.07 MIs and 1.90 strokes per 1,000 unvaccinated person-years based on ICD-9 codes.
Even with propensity scoring to minimize selection bias, no clear evidence of benefit was observed. One significant limitation is that 80% of the unvaccinated patients were younger than 60 years old, whereas 74% of the vaccinated patients were 60 or older; this might represent selection bias that cannot be overcome with propensity scoring.
Bottom line: In a population of men older than age 45, pneumococcal vaccination does not appear to reduce the risk of acute MI or stroke.
Citation: Tseng HF, Slezak JM, Quinn VP, et al. Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men. JAMA. 2010;303(17):1699-1706.
No Durable Mortality Benefit from Endovascular Repair of Enlarged Abdominal Aortic Aneurysm
Clinical question: What is the cost and mortality benefit of endovascular versus open repair of abdominal aneurysms?
Background: Previous studies demonstrated a 30-day mortality benefit using endovascular repair over open surgical repair of large abdominal aortic aneurysms. Limited longer-term data are available assessing the durability of these findings.
Study design: Randomized controlled trial.
Setting: Thirty-seven hospitals in the United Kingdom.
Synopsis: Researchers looked at 1,252 patients who were at least 60 years old with a large abdominal aortic aneurysm (>5.5 cm) on CT scan. The patients were randomized to open versus endovascular repair and followed for a median of six years postoperatively. An early, postoperative, all-cause mortality benefit was observed for endovascular repair (1.8%) compared with open repair (4.3%), but no benefit was seen after six months of follow-up, driven by secondary aneurysm ruptures with endovascular grafts. Graft-related complications in all time periods were higher in the endovascular repair group, highest from 0 to 6 months (nearly 50% of patients), and were associated with an increased cost.
Bottom line: Immediate postoperative mortality benefit of endovascular repair is not sustained for abdominal aortic aneurysm beyond six months postoperatively.
Citation: The United Kingdom EVAR trial investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010:362(20):1863-1870.
Financial Constraints Delay Presentation in Patients Suffering from Acute Myocardial Infarction
Clinical question: Does being underinsured or uninsured delay individuals from seeking treatment for emergency medical care?
Background: The number of underinsured or uninsured Americans is growing. Studies have shown that patients with financial concerns avoid routine preventive and chronic medical care; however, similar avoidance has not been defined clearly for patients seeking emergent care.
Study design: Prospective cohort study.
Setting: Twenty-four urban hospitals in the U.S. included in a multisite, acute myocardial infarction (AMI) registry.
Synopsis: Of the 3,721 patients enrolled in the AMI registry, 61.7% of the cohort was insured and without financial concerns that prevented them from seeking care. These patients were less likely to have delays in care related to AMI compared with patients who were insured with financial concerns (18.5% of the cohort; OR 1.22; 95% confidence interval [CI], 1.06-1.40) or uninsured (19.8%; OR 1.30; 95% CI, 1.12-1.51) in all time frames after symptom onset. Patients were less likely to undergo PCI or thrombolysis if the delay to presentation was more than six hours.
After adjustment for confounding factors, the authors concluded that uninsured and underinsured patients were likely to delay presentation to the hospital. Despite these findings, alternative etiologies for delays in care are likely to be more significant, as insurance considerations only account for an 8% difference between the well-insured group (39.3% delayed seeking care >6 hours) and the uninsured group (48.6%). These etiologies are ill-defined.
Bottom line: Underinsured or uninsured patients have a small but significant delay in seeking treatment for AMI due to financial concerns.
Citation: Smolderen KG, Spertus JA, Nallamothu BK, et al. Health care insurance, financial concerns in accessing care, and delays to hospital presentation in acute myocardial infarction. JAMA. 2010;303 (14):1392-1400.
Concurrent Use of PPIs and Clopidogrel Decrease Hospitalizations for Gastroduodenal Bleeding without Significant Increase in Adverse Cardiovascular Events
Clinical question: Does concomitant use of proton-pump inhibitors (PPIs) and clopidogrel affect the risks of hospitalizations for gastroduodenal bleeding and serious cardiovascular events?
Background: PPIs commonly are prescribed with clopidogrel to reduce the risk of serious gastroduodenal bleeding. Recent observational studies suggest that concurrent PPI and clopidogrel administration might increase the risk of cardiovascular events compared with clopidogrel alone.
Study design: Retrospective cohort.
Setting: Tennessee Medicaid program.
Synopsis: Researchers identified 20,596 patients hospitalized for acute MI, revascularization, or unstable angina, and prescribed clopidogrel. Of this cohort, 7,593 were initial concurrent PPI users—62% used pantoprazole and 9% used omeprazole. Hospitalizations for gastroduodenal bleeding were reduced by 50% (HR 0.50 [95% CI, 0.39-0.65]) in concurrent users of PPIs and clopidogrel, compared with nonusers of PPIs.
Concurrent use was not associated with a statistically significant increase in serious cardiovascular diseases (HR, 0.99 [95% CI, 0.82-1.19]), defined as acute MI, sudden cardiac death, nonfatal or fatal stroke, or other cardiovascular deaths.
Subgroup analyses of individual PPIs and patients undergoing percutaneous coronary interventions also showed no increased risk of serious cardiovascular events. This study could differ from previous observational studies because far fewer patients were on omeprazole, the most potent inhibitor of clopidogrel.
Bottom line: In patients treated with clopidogrel, PPI users had 50% fewer hospitalizations for gastroduodenal bleeding compared with nonusers. Concurrent use of clopidogrel and PPIs, most of which was pantoprazole, was not associated with a significant increase in serious cardiovascular events.
Citation: Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors. Ann Intern Med. 2010;152(6):337-345.
CTCA a Promising, Noninvasive Option in Evaluating Patients with Suspected Coronary Artery Disease
Clinical question: How does computed tomography coronary angiography (CTCA) compare to noninvasive stress testing for diagnosing coronary artery disease (CAD)?
Background: CTCA is a newer, noninvasive test that has a high diagnostic accuracy for CAD, but its clinical role in the evaluation of patients with chest symptoms is unclear.
Study design: Observational study.
Setting: Single academic center in the Netherlands.
Synopsis: Five hundred seventeen eligible patients were evaluated with stress testing and CTCA. The patients were classified as having a low (<20%), intermediate (20%-80%), or high (>80%) pretest probability of CAD based on the Duke clinical score. Using coronary angiography as the gold standard, stress-testing was found to be less accurate than CTCA in all of the patient groups. In patients with low and intermediate pretest probabilities, a negative CTCA had a post-test probability of 0% and 1%, respectively. On the other hand, patients with an intermediate pretest probability and a positive CTCA had a post-test probability of 94% (CI, 89%-97%). In patients with an initial high pretest probability, stress-testing and CTCA confirmed disease in most cases.
The results of this study suggest that CTCA is particularly useful in evaluating patients with an intermediate pretest probability.
Patients were ineligible in this study if they had acute coronary syndromes, previous coronary stent placement, coronary artery bypass surgery, or myocardial infarction. It is important to note that because anatomic lesions seen on imaging (CTCA and coronary angiography) are not always functionally significant, CTCA might have seemed more accurate and clinically useful than it actually is. The investigators also acknowledge that further studies are necessary before CTCA can be accepted as a first-line diagnostic test.
Bottom line: In patients with an intermediate pretest probability of CAD, a negative CTCA is valuable in excluding coronary artery disease, thereby reducing the need for invasive coronary angiography in this group.
Citation: Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med. 2010;152(10):630-639. TH
PEDIATRIC HM LITerature
Neonatal Nonhemolytic Hyperbilirubinemia Not Associated with Long-Term Cognitive or Neuropsychiatric Disability
Clinical question: Is exposure to neonatal nonhemolytic hyperbilirubinemia associated with negative long-term cognitive effects?
Background: Guidelines for the treatment of neonatal hyperbilirubinemia focus on the prevention of rare but potentially devastating consequences: bilirubin encephalopathy and subsequent kernicterus. Small studies have raised concerns regarding the potential for long-term cognitive disability in infants exposed to severe hyperbilirubinemia without kernicterus. This association primarily has been noted in patients with severe hemolytic hyperbilirubinemia; the relationship in nonhemolytic cases is less clear.
Study design: Retrospective, population-based cohort study.
Setting: Fifth Military Conscription District of Denmark.
Synopsis: All 18-year-old male conscripts born from 1977 to 1983 had data extracted from a national discharge registry with respect to maximum total serum bilirubin (TSB-max) and other clinical details. Infants born <35 weeks or of multiple gestation, age >14 days at TSB-max, or with hemolytic disease were excluded. TSB-max was analyzed as a categorical and dichotomous variable. Data were then compared to a validated Danish intelligence test administered at military draft conscription and the presence of neuropsychiatric diagnoses.
Of those examined, 463 men exceeded the cutoff for TSB-max, compared with 12,718 controls. There were no significant differences between groups with respect to the presence of neuropsychiatric diagnoses or cognitive performance.
This study benefits from its population-based design and use of an inclusive national database. However, cognitive performance is notoriously difficult to study, owing to the numerous potential confounders, many of which could not be ascertained retrospectively from the registry. Additional limitations were that the Danish thresholds for phototherapy and exchange transfusion were 240 μmol/L and 340 μmol/L (or approximately 14 mg/dL and 20 mg/dL), respectively, and only 25 newborns were exposed to levels greater than 340 μmol/L.
Although no dose response association was noted between 240 μmol/L and 340 μmol/L, no conclusions may be drawn regarding significantly higher levels.
Bottom line: Neonatal nonhemolytic hyperbilirubinemia requiring phototherapy is unlikely to be associated with long-term cognitive or neuropsychiatric disability.
Citation: Ebbesen F, Ehrenstein V, Traeger M, Nielsen GL. Neonatal non-hemolytic hyperbilirubinemia: a prevalence study of adult neuropsychiatric disability and cognitive function in 463 male Danish conscripts. Arch Dis Child. 2010;95(8):583-587.
In This Edition
Literature at a Glance
A guide to this month’s studies
- Effect of early follow-up on readmission rates
- Heart rate control and outcomes in atrial fibrillation
- Pneumococcal vaccine to prevent stroke and MI
- Long-term outcomes of endovascular repair of AAA
- Insurance and outcomes in myocardial infarction
- Risk of gastrointestinal bleeding and cardiovascular outcomes with concurrent PPI and clopidogrel use
- CT in patients with suspected coronary artery disease
Reduced 30-Day Readmission Rate for Patients Discharged from Hospitals with Higher Rates of Early Follow-Up
Clinical question: Is early follow-up after discharge for heart failure associated with a reduction in readmission rates?
Background: Readmission for heart failure is very frequent and often unplanned. Early follow-up visits after discharge have been hypothesized to reduce readmissions but have been undefined.
Study design: Retrospective cohort study.
Setting: Patients with Medicare inpatient claims data linked to the OPTIMIZE-HF and GWTG-HF registries.
Synopsis: The study included 30,136 patients >65 years old with the principal discharge diagnosis of heart failure from 2003 to 2006. Hospitals were stratified into quartiles based upon the median arrival rate to “early” (within one week after discharge) follow-up appointments. Ranges of arrival rates to these appointments ranged from Quartile 1 (Q1) (<32.4% of patients) to Q4 (>44.5%). Readmission rates were highest in the lowest quartile of “early” follow-up (Q1: 23.3%; Q2: 20.5%; Q3: 20.5%; Q4: 20.5%, P<0.001). No mortality difference was seen.
The study also examined whether the physician following the patient after discharge impacted the readmission rate for these same quartiles, comparing cardiologists to generalists and comparing the same physician at discharge and follow-up (defined as “continuity”) versus different physicians. Follow-up with continuity or a cardiologist did not reduce readmissions.
Interestingly, nearly all markers of quality were best in Q1 and Q2 hospitals, which had the lowest arrival rates to appointments, which might reflect patient-centered rather than hospital-centered issues.
Bottom line: Hospitals with low “early” follow-up appointment rates after discharge have a higher readmission rate, although causality is not established.
Citation: Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303 (17):1716-1722.
Strict Heart Rate Control Is Not Necessary in Management of Chronic Atrial Fibrillation
Clinical question: Is lenient heart rate control inferior to strict heart rate control in preventing cardiovascular events in patients with chronic atrial fibrillation?
Background: Guidelines generally call for the use of medications to achieve strict heart rate control in the management of chronic atrial fibrillation, but the optimal level of heart rate control necessary to avoid cardiovascular events remains uncertain.
Study design: Prospectively randomized, noninferiority trial.
Setting: Thirty-three medical centers in the Netherlands.
Synopsis: The study looked at 614 patients with permanent atrial fibrillation; 311 patients were randomized to lenient control and 303 to strict control. Calcium channel blockers, beta-blockers, or digoxin were dose-adjusted to control heart rate below 110 beats per minute (bpm) in the lenient control group versus 80 bpm in the strict control group.
Thirty-eight patients (12.9%) in the lenient control group and 43 (14.9%) in the strict control group reached the primary composite outcome of significant cardiovascular events (death, heart failure, stroke, embolism, major bleeding, major arrhythmia, need for pacemaker, or severe drug adverse event). Although no statistical difference in the frequency of these events between groups was detected, the study was dramatically underpowered due to unanticipated low event rates.
Bottom line: Although the lenient control group had far fewer outpatient visits and a trend toward improved outcomes, no definite conclusion regarding the management of permanent atrial fibrillation can be drawn from this underpowered noninferiority trial.
Citation: Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362(15):1363-1373.
Pneumococcal Vaccine Does Not Reduce the Risk of Stroke or Myocardial Infarction
Clinical question: Does pneumococcal vaccination reduce the risk of acute myocardial infarction (MI) and stroke?
Background: Studies have demonstrated that influenza vaccination reduces the risk of cardiac and cerebrovascular events. A single study has shown similar outcomes for the pneumococcal vaccination, although the study was limited by confounders and selection bias.
Study design: Retrospective cohort.
Setting: Large HMO in California.
Synopsis: More than 84,000 men participating in the California Men’s Health Study (CMHS) and enrolled in the Kaiser Permanente health plan were categorized as unvaccinated or vaccinated with the pneumococcal vaccine. Vaccinated patients had 10.73 first MIs and 5.30 strokes per 1,000 person-years, compared with unvaccinated patients who incurred 6.07 MIs and 1.90 strokes per 1,000 unvaccinated person-years based on ICD-9 codes.
Even with propensity scoring to minimize selection bias, no clear evidence of benefit was observed. One significant limitation is that 80% of the unvaccinated patients were younger than 60 years old, whereas 74% of the vaccinated patients were 60 or older; this might represent selection bias that cannot be overcome with propensity scoring.
Bottom line: In a population of men older than age 45, pneumococcal vaccination does not appear to reduce the risk of acute MI or stroke.
Citation: Tseng HF, Slezak JM, Quinn VP, et al. Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men. JAMA. 2010;303(17):1699-1706.
No Durable Mortality Benefit from Endovascular Repair of Enlarged Abdominal Aortic Aneurysm
Clinical question: What is the cost and mortality benefit of endovascular versus open repair of abdominal aneurysms?
Background: Previous studies demonstrated a 30-day mortality benefit using endovascular repair over open surgical repair of large abdominal aortic aneurysms. Limited longer-term data are available assessing the durability of these findings.
Study design: Randomized controlled trial.
Setting: Thirty-seven hospitals in the United Kingdom.
Synopsis: Researchers looked at 1,252 patients who were at least 60 years old with a large abdominal aortic aneurysm (>5.5 cm) on CT scan. The patients were randomized to open versus endovascular repair and followed for a median of six years postoperatively. An early, postoperative, all-cause mortality benefit was observed for endovascular repair (1.8%) compared with open repair (4.3%), but no benefit was seen after six months of follow-up, driven by secondary aneurysm ruptures with endovascular grafts. Graft-related complications in all time periods were higher in the endovascular repair group, highest from 0 to 6 months (nearly 50% of patients), and were associated with an increased cost.
Bottom line: Immediate postoperative mortality benefit of endovascular repair is not sustained for abdominal aortic aneurysm beyond six months postoperatively.
Citation: The United Kingdom EVAR trial investigators. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010:362(20):1863-1870.
Financial Constraints Delay Presentation in Patients Suffering from Acute Myocardial Infarction
Clinical question: Does being underinsured or uninsured delay individuals from seeking treatment for emergency medical care?
Background: The number of underinsured or uninsured Americans is growing. Studies have shown that patients with financial concerns avoid routine preventive and chronic medical care; however, similar avoidance has not been defined clearly for patients seeking emergent care.
Study design: Prospective cohort study.
Setting: Twenty-four urban hospitals in the U.S. included in a multisite, acute myocardial infarction (AMI) registry.
Synopsis: Of the 3,721 patients enrolled in the AMI registry, 61.7% of the cohort was insured and without financial concerns that prevented them from seeking care. These patients were less likely to have delays in care related to AMI compared with patients who were insured with financial concerns (18.5% of the cohort; OR 1.22; 95% confidence interval [CI], 1.06-1.40) or uninsured (19.8%; OR 1.30; 95% CI, 1.12-1.51) in all time frames after symptom onset. Patients were less likely to undergo PCI or thrombolysis if the delay to presentation was more than six hours.
After adjustment for confounding factors, the authors concluded that uninsured and underinsured patients were likely to delay presentation to the hospital. Despite these findings, alternative etiologies for delays in care are likely to be more significant, as insurance considerations only account for an 8% difference between the well-insured group (39.3% delayed seeking care >6 hours) and the uninsured group (48.6%). These etiologies are ill-defined.
Bottom line: Underinsured or uninsured patients have a small but significant delay in seeking treatment for AMI due to financial concerns.
Citation: Smolderen KG, Spertus JA, Nallamothu BK, et al. Health care insurance, financial concerns in accessing care, and delays to hospital presentation in acute myocardial infarction. JAMA. 2010;303 (14):1392-1400.
Concurrent Use of PPIs and Clopidogrel Decrease Hospitalizations for Gastroduodenal Bleeding without Significant Increase in Adverse Cardiovascular Events
Clinical question: Does concomitant use of proton-pump inhibitors (PPIs) and clopidogrel affect the risks of hospitalizations for gastroduodenal bleeding and serious cardiovascular events?
Background: PPIs commonly are prescribed with clopidogrel to reduce the risk of serious gastroduodenal bleeding. Recent observational studies suggest that concurrent PPI and clopidogrel administration might increase the risk of cardiovascular events compared with clopidogrel alone.
Study design: Retrospective cohort.
Setting: Tennessee Medicaid program.
Synopsis: Researchers identified 20,596 patients hospitalized for acute MI, revascularization, or unstable angina, and prescribed clopidogrel. Of this cohort, 7,593 were initial concurrent PPI users—62% used pantoprazole and 9% used omeprazole. Hospitalizations for gastroduodenal bleeding were reduced by 50% (HR 0.50 [95% CI, 0.39-0.65]) in concurrent users of PPIs and clopidogrel, compared with nonusers of PPIs.
Concurrent use was not associated with a statistically significant increase in serious cardiovascular diseases (HR, 0.99 [95% CI, 0.82-1.19]), defined as acute MI, sudden cardiac death, nonfatal or fatal stroke, or other cardiovascular deaths.
Subgroup analyses of individual PPIs and patients undergoing percutaneous coronary interventions also showed no increased risk of serious cardiovascular events. This study could differ from previous observational studies because far fewer patients were on omeprazole, the most potent inhibitor of clopidogrel.
Bottom line: In patients treated with clopidogrel, PPI users had 50% fewer hospitalizations for gastroduodenal bleeding compared with nonusers. Concurrent use of clopidogrel and PPIs, most of which was pantoprazole, was not associated with a significant increase in serious cardiovascular events.
Citation: Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors. Ann Intern Med. 2010;152(6):337-345.
CTCA a Promising, Noninvasive Option in Evaluating Patients with Suspected Coronary Artery Disease
Clinical question: How does computed tomography coronary angiography (CTCA) compare to noninvasive stress testing for diagnosing coronary artery disease (CAD)?
Background: CTCA is a newer, noninvasive test that has a high diagnostic accuracy for CAD, but its clinical role in the evaluation of patients with chest symptoms is unclear.
Study design: Observational study.
Setting: Single academic center in the Netherlands.
Synopsis: Five hundred seventeen eligible patients were evaluated with stress testing and CTCA. The patients were classified as having a low (<20%), intermediate (20%-80%), or high (>80%) pretest probability of CAD based on the Duke clinical score. Using coronary angiography as the gold standard, stress-testing was found to be less accurate than CTCA in all of the patient groups. In patients with low and intermediate pretest probabilities, a negative CTCA had a post-test probability of 0% and 1%, respectively. On the other hand, patients with an intermediate pretest probability and a positive CTCA had a post-test probability of 94% (CI, 89%-97%). In patients with an initial high pretest probability, stress-testing and CTCA confirmed disease in most cases.
The results of this study suggest that CTCA is particularly useful in evaluating patients with an intermediate pretest probability.
Patients were ineligible in this study if they had acute coronary syndromes, previous coronary stent placement, coronary artery bypass surgery, or myocardial infarction. It is important to note that because anatomic lesions seen on imaging (CTCA and coronary angiography) are not always functionally significant, CTCA might have seemed more accurate and clinically useful than it actually is. The investigators also acknowledge that further studies are necessary before CTCA can be accepted as a first-line diagnostic test.
Bottom line: In patients with an intermediate pretest probability of CAD, a negative CTCA is valuable in excluding coronary artery disease, thereby reducing the need for invasive coronary angiography in this group.
Citation: Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med. 2010;152(10):630-639. TH
PEDIATRIC HM LITerature
Neonatal Nonhemolytic Hyperbilirubinemia Not Associated with Long-Term Cognitive or Neuropsychiatric Disability
Clinical question: Is exposure to neonatal nonhemolytic hyperbilirubinemia associated with negative long-term cognitive effects?
Background: Guidelines for the treatment of neonatal hyperbilirubinemia focus on the prevention of rare but potentially devastating consequences: bilirubin encephalopathy and subsequent kernicterus. Small studies have raised concerns regarding the potential for long-term cognitive disability in infants exposed to severe hyperbilirubinemia without kernicterus. This association primarily has been noted in patients with severe hemolytic hyperbilirubinemia; the relationship in nonhemolytic cases is less clear.
Study design: Retrospective, population-based cohort study.
Setting: Fifth Military Conscription District of Denmark.
Synopsis: All 18-year-old male conscripts born from 1977 to 1983 had data extracted from a national discharge registry with respect to maximum total serum bilirubin (TSB-max) and other clinical details. Infants born <35 weeks or of multiple gestation, age >14 days at TSB-max, or with hemolytic disease were excluded. TSB-max was analyzed as a categorical and dichotomous variable. Data were then compared to a validated Danish intelligence test administered at military draft conscription and the presence of neuropsychiatric diagnoses.
Of those examined, 463 men exceeded the cutoff for TSB-max, compared with 12,718 controls. There were no significant differences between groups with respect to the presence of neuropsychiatric diagnoses or cognitive performance.
This study benefits from its population-based design and use of an inclusive national database. However, cognitive performance is notoriously difficult to study, owing to the numerous potential confounders, many of which could not be ascertained retrospectively from the registry. Additional limitations were that the Danish thresholds for phototherapy and exchange transfusion were 240 μmol/L and 340 μmol/L (or approximately 14 mg/dL and 20 mg/dL), respectively, and only 25 newborns were exposed to levels greater than 340 μmol/L.
Although no dose response association was noted between 240 μmol/L and 340 μmol/L, no conclusions may be drawn regarding significantly higher levels.
Bottom line: Neonatal nonhemolytic hyperbilirubinemia requiring phototherapy is unlikely to be associated with long-term cognitive or neuropsychiatric disability.
Citation: Ebbesen F, Ehrenstein V, Traeger M, Nielsen GL. Neonatal non-hemolytic hyperbilirubinemia: a prevalence study of adult neuropsychiatric disability and cognitive function in 463 male Danish conscripts. Arch Dis Child. 2010;95(8):583-587.