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Ezetimibe’s ACS benefit centers on high-risk, post-CABG patients
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: The absolute primary-event risk reduction was 9% in post-CABG patients and 1% in all other patients.
Data source: An exploratory, post-hoc analysis of data collected in IMPROVE-IT, a multicenter trial with 18,144 patients.
Disclosures: IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
Joint European atrial fibrillation guidelines break new ground
ROME – The 2016 joint European guidelines on management of atrial fibrillation break new ground by declaring as a strong Class IA recommendation that the novel oral anticoagulants are now the drugs of choice – preferred over warfarin – for stroke prevention.
The joint guidelines from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery recommend that warfarin’s use be reserved for the relatively small proportion of atrial fibrillation (AF) patients who are ineligible for the four commercially available novel oral anticoagulants (NOACs). That’s mainly patients with mechanical heart valves, moderate to severe mitral stenosis, or severe chronic kidney disease.
The ESC/EACTS guidelines, taken together with the American College of Chest Physicians guidelines on antithrombotic therapy for venous thromboembolic disease released earlier in the year, suggest that the old war horse warfarin is being eased out to pasture. The ACCP guidelines recommend any of the four NOACS – apixaban, dabigatran, edoxaban, or rivaroxaban – be used preferentially over warfarin in the treatment of venous thromboembolism (Chest 2016 Feb;149[2]:315-52). Both sets of guidelines cite compelling evidence that the NOACs are significantly safer than warfarin yet equally effective.
The ESC/EACTS guidelines are a full rewrite containing numerous departures from the previous 2012 AF management guidelines as well as from current ACC/AHA guidelines. The report includes more than 1,000 references. Eighty percent of the 154 recommendations provide Class I or IIa guidance. Two-thirds of the recommendations are Level of Evidence A or B, task force chairperson Paulus Kirchhof, MD, said at the annual congress of the European Society of Cardiology.
He and co-chairperson Stefano Benussi, MD, presented some of the highlights.
The guidelines issue a strong call for greater use of targeted ECG screening in populations at risk for silent AF, including stroke survivors and the elderly. And AF should always be documented before starting treatment, given that all of the treatments carry risk, said Dr. Kirchhof, professor of cardiovascular medicine at the University of Birmingham (England).
Once the diagnosis is established, it’s essential to address in a structured way five domains of management: acute rate and rhythm control; management of precipitating factors, including underlying cardiovascular conditions such as hypertension or valvular heart disease; assessment of stroke risk using the CHA2DS2-VASc scoring system; assessment of heart rate; and evaluation of the impact of AF symptoms on the patient’s life, including fatigue and breathlessness, using a structured instrument such as the modified European Heart Rhythm Association symptom scale.
Men with a CHA2DS2-VASc score of 1 and women with a score of 2 should be considered for anticoagulation. And the treatment should be recommended – not merely considered – for men with a score of 2 or more and women with a score of 3; that’s a Class Ia recommendation, Dr. Kirchhof continued.
The use of a specific bleeding risk score is no longer recommended in AF patients on oral anticoagulation. The emphasis has shifted to reduction of modifiable bleeding risk factors, including limiting alcohol intake to fewer than 8 drinks per week, control of hypertension, and discontinuing antiplatelet and anti-inflammatory agents.
Consideration of left atrial appendage occlusion devices should be reserved for the small percentage of patients who have clear contraindications to all forms of oral anticoagulation.
The task force concluded that patients who have bleeding on oral anticoagulation can often be managed with local therapy and discontinuation of anticoagulation therapy for a day or two before resumption. However, decisions regarding resumption of a NOAC or warfarin after an intracranial bleed should be handled by an interdisciplinary panel composed of a stroke neurologist, a cardiologist, a neuroradiologist, and a neurosurgeon.
Evidence-based treatment options in patients with symptomatic AF after failed catheter ablation include minimally invasive surgery with epicardial pulmonary vein isolation, more extensive catheter ablation, and hybrid procedures, according to Dr. Benussi, who is codirector of clinical cardiovascular surgery at University Hospital in Zurich.
The guidelines state that the data supporting catheter ablation to achieve long-term rhythm control are now sufficiently strong that this intervention should be considered as a first-line option alongside antiarrhythmic drugs as a matter of patient preference in the setting of symptomatic paroxysmal AF regardless of whether the patient has CAD, heart failure, valvular heart disease, or no structural heart disease.
Catheter ablation using radiofrequency energy or cryoablation should target complete isolation of the pulmonary veins.
“Additional ablation lines do not provide demonstrable clinical benefit and increase the risk of postablation left atrial arrhythmias,” the surgeon said.
Maze surgery, preferably biatrial, received a favorable Class IIa, Level of Evidence A recommendation as worthy of consideration in patients with symptomatic AF who are already undergoing cardiac surgery. This recommendation was based upon an external review by the Cochrane group which was commissioned by the guidelines task force. The Cochrane review of eight published studies concluded that Maze surgery under such circumstances was associated with a twofold increased freedom from AF, atrial flutter, and atrial tachycardia (Cochrane Database of Systematic Reviews 2016;8: CD012088. doi: 10.1002/14651858.CD012088.pub2).
The AF management guidelines are supported by the ESC Pocket Guidelines app, which includes an overall AF treatment manager developed by the European Union–funded CATCH ME (Characterizing Atrial Fibrillation by Translating its Causes Into Health Modifiers in the Elderly) project.
The multidisciplinary 17-member AF management task force was drawn from cardiology, stroke neurology, cardiac surgery, and specialist nursing. Dr. Kirchhof stressed that only recommendations supported by at least 75% of task force members made it into the guidelines (Eur Heart J. 2016 Aug 27. pii: ehw210. [Epub ahead of print] doi: 10.1093/eurheartj/ehw210).
ROME – The 2016 joint European guidelines on management of atrial fibrillation break new ground by declaring as a strong Class IA recommendation that the novel oral anticoagulants are now the drugs of choice – preferred over warfarin – for stroke prevention.
The joint guidelines from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery recommend that warfarin’s use be reserved for the relatively small proportion of atrial fibrillation (AF) patients who are ineligible for the four commercially available novel oral anticoagulants (NOACs). That’s mainly patients with mechanical heart valves, moderate to severe mitral stenosis, or severe chronic kidney disease.
The ESC/EACTS guidelines, taken together with the American College of Chest Physicians guidelines on antithrombotic therapy for venous thromboembolic disease released earlier in the year, suggest that the old war horse warfarin is being eased out to pasture. The ACCP guidelines recommend any of the four NOACS – apixaban, dabigatran, edoxaban, or rivaroxaban – be used preferentially over warfarin in the treatment of venous thromboembolism (Chest 2016 Feb;149[2]:315-52). Both sets of guidelines cite compelling evidence that the NOACs are significantly safer than warfarin yet equally effective.
The ESC/EACTS guidelines are a full rewrite containing numerous departures from the previous 2012 AF management guidelines as well as from current ACC/AHA guidelines. The report includes more than 1,000 references. Eighty percent of the 154 recommendations provide Class I or IIa guidance. Two-thirds of the recommendations are Level of Evidence A or B, task force chairperson Paulus Kirchhof, MD, said at the annual congress of the European Society of Cardiology.
He and co-chairperson Stefano Benussi, MD, presented some of the highlights.
The guidelines issue a strong call for greater use of targeted ECG screening in populations at risk for silent AF, including stroke survivors and the elderly. And AF should always be documented before starting treatment, given that all of the treatments carry risk, said Dr. Kirchhof, professor of cardiovascular medicine at the University of Birmingham (England).
Once the diagnosis is established, it’s essential to address in a structured way five domains of management: acute rate and rhythm control; management of precipitating factors, including underlying cardiovascular conditions such as hypertension or valvular heart disease; assessment of stroke risk using the CHA2DS2-VASc scoring system; assessment of heart rate; and evaluation of the impact of AF symptoms on the patient’s life, including fatigue and breathlessness, using a structured instrument such as the modified European Heart Rhythm Association symptom scale.
Men with a CHA2DS2-VASc score of 1 and women with a score of 2 should be considered for anticoagulation. And the treatment should be recommended – not merely considered – for men with a score of 2 or more and women with a score of 3; that’s a Class Ia recommendation, Dr. Kirchhof continued.
The use of a specific bleeding risk score is no longer recommended in AF patients on oral anticoagulation. The emphasis has shifted to reduction of modifiable bleeding risk factors, including limiting alcohol intake to fewer than 8 drinks per week, control of hypertension, and discontinuing antiplatelet and anti-inflammatory agents.
Consideration of left atrial appendage occlusion devices should be reserved for the small percentage of patients who have clear contraindications to all forms of oral anticoagulation.
The task force concluded that patients who have bleeding on oral anticoagulation can often be managed with local therapy and discontinuation of anticoagulation therapy for a day or two before resumption. However, decisions regarding resumption of a NOAC or warfarin after an intracranial bleed should be handled by an interdisciplinary panel composed of a stroke neurologist, a cardiologist, a neuroradiologist, and a neurosurgeon.
Evidence-based treatment options in patients with symptomatic AF after failed catheter ablation include minimally invasive surgery with epicardial pulmonary vein isolation, more extensive catheter ablation, and hybrid procedures, according to Dr. Benussi, who is codirector of clinical cardiovascular surgery at University Hospital in Zurich.
The guidelines state that the data supporting catheter ablation to achieve long-term rhythm control are now sufficiently strong that this intervention should be considered as a first-line option alongside antiarrhythmic drugs as a matter of patient preference in the setting of symptomatic paroxysmal AF regardless of whether the patient has CAD, heart failure, valvular heart disease, or no structural heart disease.
Catheter ablation using radiofrequency energy or cryoablation should target complete isolation of the pulmonary veins.
“Additional ablation lines do not provide demonstrable clinical benefit and increase the risk of postablation left atrial arrhythmias,” the surgeon said.
Maze surgery, preferably biatrial, received a favorable Class IIa, Level of Evidence A recommendation as worthy of consideration in patients with symptomatic AF who are already undergoing cardiac surgery. This recommendation was based upon an external review by the Cochrane group which was commissioned by the guidelines task force. The Cochrane review of eight published studies concluded that Maze surgery under such circumstances was associated with a twofold increased freedom from AF, atrial flutter, and atrial tachycardia (Cochrane Database of Systematic Reviews 2016;8: CD012088. doi: 10.1002/14651858.CD012088.pub2).
The AF management guidelines are supported by the ESC Pocket Guidelines app, which includes an overall AF treatment manager developed by the European Union–funded CATCH ME (Characterizing Atrial Fibrillation by Translating its Causes Into Health Modifiers in the Elderly) project.
The multidisciplinary 17-member AF management task force was drawn from cardiology, stroke neurology, cardiac surgery, and specialist nursing. Dr. Kirchhof stressed that only recommendations supported by at least 75% of task force members made it into the guidelines (Eur Heart J. 2016 Aug 27. pii: ehw210. [Epub ahead of print] doi: 10.1093/eurheartj/ehw210).
ROME – The 2016 joint European guidelines on management of atrial fibrillation break new ground by declaring as a strong Class IA recommendation that the novel oral anticoagulants are now the drugs of choice – preferred over warfarin – for stroke prevention.
The joint guidelines from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery recommend that warfarin’s use be reserved for the relatively small proportion of atrial fibrillation (AF) patients who are ineligible for the four commercially available novel oral anticoagulants (NOACs). That’s mainly patients with mechanical heart valves, moderate to severe mitral stenosis, or severe chronic kidney disease.
The ESC/EACTS guidelines, taken together with the American College of Chest Physicians guidelines on antithrombotic therapy for venous thromboembolic disease released earlier in the year, suggest that the old war horse warfarin is being eased out to pasture. The ACCP guidelines recommend any of the four NOACS – apixaban, dabigatran, edoxaban, or rivaroxaban – be used preferentially over warfarin in the treatment of venous thromboembolism (Chest 2016 Feb;149[2]:315-52). Both sets of guidelines cite compelling evidence that the NOACs are significantly safer than warfarin yet equally effective.
The ESC/EACTS guidelines are a full rewrite containing numerous departures from the previous 2012 AF management guidelines as well as from current ACC/AHA guidelines. The report includes more than 1,000 references. Eighty percent of the 154 recommendations provide Class I or IIa guidance. Two-thirds of the recommendations are Level of Evidence A or B, task force chairperson Paulus Kirchhof, MD, said at the annual congress of the European Society of Cardiology.
He and co-chairperson Stefano Benussi, MD, presented some of the highlights.
The guidelines issue a strong call for greater use of targeted ECG screening in populations at risk for silent AF, including stroke survivors and the elderly. And AF should always be documented before starting treatment, given that all of the treatments carry risk, said Dr. Kirchhof, professor of cardiovascular medicine at the University of Birmingham (England).
Once the diagnosis is established, it’s essential to address in a structured way five domains of management: acute rate and rhythm control; management of precipitating factors, including underlying cardiovascular conditions such as hypertension or valvular heart disease; assessment of stroke risk using the CHA2DS2-VASc scoring system; assessment of heart rate; and evaluation of the impact of AF symptoms on the patient’s life, including fatigue and breathlessness, using a structured instrument such as the modified European Heart Rhythm Association symptom scale.
Men with a CHA2DS2-VASc score of 1 and women with a score of 2 should be considered for anticoagulation. And the treatment should be recommended – not merely considered – for men with a score of 2 or more and women with a score of 3; that’s a Class Ia recommendation, Dr. Kirchhof continued.
The use of a specific bleeding risk score is no longer recommended in AF patients on oral anticoagulation. The emphasis has shifted to reduction of modifiable bleeding risk factors, including limiting alcohol intake to fewer than 8 drinks per week, control of hypertension, and discontinuing antiplatelet and anti-inflammatory agents.
Consideration of left atrial appendage occlusion devices should be reserved for the small percentage of patients who have clear contraindications to all forms of oral anticoagulation.
The task force concluded that patients who have bleeding on oral anticoagulation can often be managed with local therapy and discontinuation of anticoagulation therapy for a day or two before resumption. However, decisions regarding resumption of a NOAC or warfarin after an intracranial bleed should be handled by an interdisciplinary panel composed of a stroke neurologist, a cardiologist, a neuroradiologist, and a neurosurgeon.
Evidence-based treatment options in patients with symptomatic AF after failed catheter ablation include minimally invasive surgery with epicardial pulmonary vein isolation, more extensive catheter ablation, and hybrid procedures, according to Dr. Benussi, who is codirector of clinical cardiovascular surgery at University Hospital in Zurich.
The guidelines state that the data supporting catheter ablation to achieve long-term rhythm control are now sufficiently strong that this intervention should be considered as a first-line option alongside antiarrhythmic drugs as a matter of patient preference in the setting of symptomatic paroxysmal AF regardless of whether the patient has CAD, heart failure, valvular heart disease, or no structural heart disease.
Catheter ablation using radiofrequency energy or cryoablation should target complete isolation of the pulmonary veins.
“Additional ablation lines do not provide demonstrable clinical benefit and increase the risk of postablation left atrial arrhythmias,” the surgeon said.
Maze surgery, preferably biatrial, received a favorable Class IIa, Level of Evidence A recommendation as worthy of consideration in patients with symptomatic AF who are already undergoing cardiac surgery. This recommendation was based upon an external review by the Cochrane group which was commissioned by the guidelines task force. The Cochrane review of eight published studies concluded that Maze surgery under such circumstances was associated with a twofold increased freedom from AF, atrial flutter, and atrial tachycardia (Cochrane Database of Systematic Reviews 2016;8: CD012088. doi: 10.1002/14651858.CD012088.pub2).
The AF management guidelines are supported by the ESC Pocket Guidelines app, which includes an overall AF treatment manager developed by the European Union–funded CATCH ME (Characterizing Atrial Fibrillation by Translating its Causes Into Health Modifiers in the Elderly) project.
The multidisciplinary 17-member AF management task force was drawn from cardiology, stroke neurology, cardiac surgery, and specialist nursing. Dr. Kirchhof stressed that only recommendations supported by at least 75% of task force members made it into the guidelines (Eur Heart J. 2016 Aug 27. pii: ehw210. [Epub ahead of print] doi: 10.1093/eurheartj/ehw210).
Study links low diastolic blood pressure to myocardial damage, coronary heart disease
Low diastolic blood pressure (DBP) was significantly associated with myocardial injury and incident coronary heart disease, especially when the systolic blood pressure was 120 mm or higher, investigators reported.
Compared with a DBP of 80 to 89 mm Hg, DBP below 60 mm Hg more than doubled the odds of high-sensitivity cardiac troponin-T levels equaling or exceeding 14 ng per mL, and increased the risk of incident coronary heart disease (CHD) by about 50%, in a large observational study. Associations were strongest when baseline systolic blood pressure was at least 120 mm Hg, signifying elevated pulse pressure, reported Dr. John McEvoy of the Ciccarone Center for the Prevention of Heart Disease, Hopkins University, Baltimore, and associates (J Am Coll Cardiol 2016;68[16]:1713–22).
Their study included 11,565 individuals tracked for 21 years through the Atherosclerosis Risk in Communities Cohort, an observational population-based study of adults from in North Carolina, Mississippi, Minnesota, and Maryland. The researchers excluded participants with known baseline cardiovascular disease or heart failure. High-sensitivity cardiac troponin-T levels were measured at three time points between 1990 and 1992, 1996 and 1998, and 2011 and 2013. Participants averaged 57 years old at enrollment, 57% were female, and 25% were black (J Am Coll Cardiol. 2016 Oct 18. doi: 10.1016/j.jacc.2016.07.754).
Compared with baseline DBP of 80 to 89 mm Hg, DBP under 60 mm Hg was associated with a 2.2-fold greater odds (P = .01) of high-sensitivity cardiac troponin-T levels equal to or exceeding 14 ng per mL during the same visit – indicating prevalent myocardial damage – even after controlling for race, sex, body mass index, smoking and alcohol use, triglyceride and cholesterol levels, diabetes, glomerular filtration rate, and use of antihypertensives and lipid-lowering drugs, said the researchers. The odds of myocardial damage remained increased even when DBP was 60 to 69 mm Hg (odds ratio, 1.5; P = .05). Low DBP also was associated with myocardial damage at any given systolic blood pressure.
Furthermore, low DBP significantly increased the risk of progressively worsening myocardial damage, as indicated by a rising annual change in high-sensitivity cardiac troponin-T levels over 6 years. The association was significant as long as DBP was under 80 mm Hg, but was strongest when DBP was less than 60 mm Hg. Diastolic blood pressure under 60 mm Hg also significantly increased the chances of incident CHD and death, but not stroke.
Low DBP was most strongly linked to subclinical myocardial damage and incident CHD when systolic blood pressure was at least 120 mm Hg, indicating elevated pulse pressure, the researchers reported. Systolic pressure is “the main determinant of cardiac afterload and, thus, a primary driver of myocardial energy requirements,” while low DBP reduces myocardial energy supply, they noted. Therefore, high pulse pressure would lead to the greatest mismatch between myocardial energy demand and supply.
“Among patients being treated to SBP goals of 140 mm Hg or lower, attention may need to be paid not only to SBP, but also, importantly, to achieved DBP. Diastolic and systolic BP are inextricably linked, and our results highlighted the importance of not ignoring the former and focusing only on the latter, instead emphasizing the need to consider both in the optimal treatment of adults with hypertension.,”
The study was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by the National Heart, Lung, and Blood Institute. Roche Diagnostics provided reagents for the cardiac troponin assays. Dr. McEvoy had no disclosures. One author disclosed ties to Roche; one author disclosed ties to Roche, Abbott Diagnostics, and several other relevant companies; and two authors are coinvestigators on a provisional patent filed by Roche for use of biomarkers in predicting heart failure. The other four authors had no disclosures.
The average age in the study by McEvoy et al. was 57 years. One might anticipate that in an older population, the side effects from lower BPs [blood pressures] due to drug therapy such as hypotension or syncope would be greater, and the potential for adverse cardiovascular events due to a J-curve would be substantially increased compared with what was seen in the present study. Similarly, an exacerbated potential for lower DBP to be harmful might be expected in patients with established coronary artery disease.
The well done study ... shows that lower may not always be better with respect to blood pressure control and, along with other accumulating evidence, strongly suggests careful thought before pushing blood pressure control below current guideline targets, especially if the diastolic blood pressure falls below 60 mm Hg while the pulse pressure is[greater than] 60 mm Hg.
Deepak L. Bhatt, MD, MPH, is at Brigham and Women’s Hospital Heart & Vascular Center, Boston. He disclosed ties to Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, and a number of other pharmaceutical and medical education companies. His comments are from an accompanying editorial (J Am Coll Cardiol. 2016 Oct 18;68[16]:1723-1726).
The average age in the study by McEvoy et al. was 57 years. One might anticipate that in an older population, the side effects from lower BPs [blood pressures] due to drug therapy such as hypotension or syncope would be greater, and the potential for adverse cardiovascular events due to a J-curve would be substantially increased compared with what was seen in the present study. Similarly, an exacerbated potential for lower DBP to be harmful might be expected in patients with established coronary artery disease.
The well done study ... shows that lower may not always be better with respect to blood pressure control and, along with other accumulating evidence, strongly suggests careful thought before pushing blood pressure control below current guideline targets, especially if the diastolic blood pressure falls below 60 mm Hg while the pulse pressure is[greater than] 60 mm Hg.
Deepak L. Bhatt, MD, MPH, is at Brigham and Women’s Hospital Heart & Vascular Center, Boston. He disclosed ties to Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, and a number of other pharmaceutical and medical education companies. His comments are from an accompanying editorial (J Am Coll Cardiol. 2016 Oct 18;68[16]:1723-1726).
The average age in the study by McEvoy et al. was 57 years. One might anticipate that in an older population, the side effects from lower BPs [blood pressures] due to drug therapy such as hypotension or syncope would be greater, and the potential for adverse cardiovascular events due to a J-curve would be substantially increased compared with what was seen in the present study. Similarly, an exacerbated potential for lower DBP to be harmful might be expected in patients with established coronary artery disease.
The well done study ... shows that lower may not always be better with respect to blood pressure control and, along with other accumulating evidence, strongly suggests careful thought before pushing blood pressure control below current guideline targets, especially if the diastolic blood pressure falls below 60 mm Hg while the pulse pressure is[greater than] 60 mm Hg.
Deepak L. Bhatt, MD, MPH, is at Brigham and Women’s Hospital Heart & Vascular Center, Boston. He disclosed ties to Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, and a number of other pharmaceutical and medical education companies. His comments are from an accompanying editorial (J Am Coll Cardiol. 2016 Oct 18;68[16]:1723-1726).
Low diastolic blood pressure (DBP) was significantly associated with myocardial injury and incident coronary heart disease, especially when the systolic blood pressure was 120 mm or higher, investigators reported.
Compared with a DBP of 80 to 89 mm Hg, DBP below 60 mm Hg more than doubled the odds of high-sensitivity cardiac troponin-T levels equaling or exceeding 14 ng per mL, and increased the risk of incident coronary heart disease (CHD) by about 50%, in a large observational study. Associations were strongest when baseline systolic blood pressure was at least 120 mm Hg, signifying elevated pulse pressure, reported Dr. John McEvoy of the Ciccarone Center for the Prevention of Heart Disease, Hopkins University, Baltimore, and associates (J Am Coll Cardiol 2016;68[16]:1713–22).
Their study included 11,565 individuals tracked for 21 years through the Atherosclerosis Risk in Communities Cohort, an observational population-based study of adults from in North Carolina, Mississippi, Minnesota, and Maryland. The researchers excluded participants with known baseline cardiovascular disease or heart failure. High-sensitivity cardiac troponin-T levels were measured at three time points between 1990 and 1992, 1996 and 1998, and 2011 and 2013. Participants averaged 57 years old at enrollment, 57% were female, and 25% were black (J Am Coll Cardiol. 2016 Oct 18. doi: 10.1016/j.jacc.2016.07.754).
Compared with baseline DBP of 80 to 89 mm Hg, DBP under 60 mm Hg was associated with a 2.2-fold greater odds (P = .01) of high-sensitivity cardiac troponin-T levels equal to or exceeding 14 ng per mL during the same visit – indicating prevalent myocardial damage – even after controlling for race, sex, body mass index, smoking and alcohol use, triglyceride and cholesterol levels, diabetes, glomerular filtration rate, and use of antihypertensives and lipid-lowering drugs, said the researchers. The odds of myocardial damage remained increased even when DBP was 60 to 69 mm Hg (odds ratio, 1.5; P = .05). Low DBP also was associated with myocardial damage at any given systolic blood pressure.
Furthermore, low DBP significantly increased the risk of progressively worsening myocardial damage, as indicated by a rising annual change in high-sensitivity cardiac troponin-T levels over 6 years. The association was significant as long as DBP was under 80 mm Hg, but was strongest when DBP was less than 60 mm Hg. Diastolic blood pressure under 60 mm Hg also significantly increased the chances of incident CHD and death, but not stroke.
Low DBP was most strongly linked to subclinical myocardial damage and incident CHD when systolic blood pressure was at least 120 mm Hg, indicating elevated pulse pressure, the researchers reported. Systolic pressure is “the main determinant of cardiac afterload and, thus, a primary driver of myocardial energy requirements,” while low DBP reduces myocardial energy supply, they noted. Therefore, high pulse pressure would lead to the greatest mismatch between myocardial energy demand and supply.
“Among patients being treated to SBP goals of 140 mm Hg or lower, attention may need to be paid not only to SBP, but also, importantly, to achieved DBP. Diastolic and systolic BP are inextricably linked, and our results highlighted the importance of not ignoring the former and focusing only on the latter, instead emphasizing the need to consider both in the optimal treatment of adults with hypertension.,”
The study was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by the National Heart, Lung, and Blood Institute. Roche Diagnostics provided reagents for the cardiac troponin assays. Dr. McEvoy had no disclosures. One author disclosed ties to Roche; one author disclosed ties to Roche, Abbott Diagnostics, and several other relevant companies; and two authors are coinvestigators on a provisional patent filed by Roche for use of biomarkers in predicting heart failure. The other four authors had no disclosures.
Low diastolic blood pressure (DBP) was significantly associated with myocardial injury and incident coronary heart disease, especially when the systolic blood pressure was 120 mm or higher, investigators reported.
Compared with a DBP of 80 to 89 mm Hg, DBP below 60 mm Hg more than doubled the odds of high-sensitivity cardiac troponin-T levels equaling or exceeding 14 ng per mL, and increased the risk of incident coronary heart disease (CHD) by about 50%, in a large observational study. Associations were strongest when baseline systolic blood pressure was at least 120 mm Hg, signifying elevated pulse pressure, reported Dr. John McEvoy of the Ciccarone Center for the Prevention of Heart Disease, Hopkins University, Baltimore, and associates (J Am Coll Cardiol 2016;68[16]:1713–22).
Their study included 11,565 individuals tracked for 21 years through the Atherosclerosis Risk in Communities Cohort, an observational population-based study of adults from in North Carolina, Mississippi, Minnesota, and Maryland. The researchers excluded participants with known baseline cardiovascular disease or heart failure. High-sensitivity cardiac troponin-T levels were measured at three time points between 1990 and 1992, 1996 and 1998, and 2011 and 2013. Participants averaged 57 years old at enrollment, 57% were female, and 25% were black (J Am Coll Cardiol. 2016 Oct 18. doi: 10.1016/j.jacc.2016.07.754).
Compared with baseline DBP of 80 to 89 mm Hg, DBP under 60 mm Hg was associated with a 2.2-fold greater odds (P = .01) of high-sensitivity cardiac troponin-T levels equal to or exceeding 14 ng per mL during the same visit – indicating prevalent myocardial damage – even after controlling for race, sex, body mass index, smoking and alcohol use, triglyceride and cholesterol levels, diabetes, glomerular filtration rate, and use of antihypertensives and lipid-lowering drugs, said the researchers. The odds of myocardial damage remained increased even when DBP was 60 to 69 mm Hg (odds ratio, 1.5; P = .05). Low DBP also was associated with myocardial damage at any given systolic blood pressure.
Furthermore, low DBP significantly increased the risk of progressively worsening myocardial damage, as indicated by a rising annual change in high-sensitivity cardiac troponin-T levels over 6 years. The association was significant as long as DBP was under 80 mm Hg, but was strongest when DBP was less than 60 mm Hg. Diastolic blood pressure under 60 mm Hg also significantly increased the chances of incident CHD and death, but not stroke.
Low DBP was most strongly linked to subclinical myocardial damage and incident CHD when systolic blood pressure was at least 120 mm Hg, indicating elevated pulse pressure, the researchers reported. Systolic pressure is “the main determinant of cardiac afterload and, thus, a primary driver of myocardial energy requirements,” while low DBP reduces myocardial energy supply, they noted. Therefore, high pulse pressure would lead to the greatest mismatch between myocardial energy demand and supply.
“Among patients being treated to SBP goals of 140 mm Hg or lower, attention may need to be paid not only to SBP, but also, importantly, to achieved DBP. Diastolic and systolic BP are inextricably linked, and our results highlighted the importance of not ignoring the former and focusing only on the latter, instead emphasizing the need to consider both in the optimal treatment of adults with hypertension.,”
The study was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by the National Heart, Lung, and Blood Institute. Roche Diagnostics provided reagents for the cardiac troponin assays. Dr. McEvoy had no disclosures. One author disclosed ties to Roche; one author disclosed ties to Roche, Abbott Diagnostics, and several other relevant companies; and two authors are coinvestigators on a provisional patent filed by Roche for use of biomarkers in predicting heart failure. The other four authors had no disclosures.
From the Journal of the American College of Cardiology
Key clinical point: Low diastolic blood pressure is associated with myocardial injury and incident coronary heart disease.
Major finding: Diastolic blood pressure below 60 mm Hg more than doubled the odds of high-sensitivity cardiac troponin-T levels equaling or exceeding 14 ng per mL and increased the risk of incident coronary heart disease by about 50%, compared to diastolic blood pressure of 80 to 89 mm Hg. Associations were strongest when pressure was elevated (above 60 mm Hg).
Data source: A prospective observational study of 11,565 adults followed for 21 years as part of the Atherosclerosis Risk in Communities cohort.
Disclosures: The study was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and by the National Heart, Lung, and Blood Institute. Roche Diagnostics provided reagents for the cardiac troponin assays. Dr. McEvoy had no disclosures. One author disclosed ties to Roche; one author disclosed ties to Roche, Abbott Diagnostics, and several other relevant companies; and two authors are coinvestigators on a provisional patent filed by Roche for use of biomarkers in predicting heart failure. The other four authors had no disclosures.
SAVR for radiation-induced aortic stenosis has high late mortality
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
ROME – Radiation-induced aortic stenosis is associated with markedly worse long-term outcome after surgical aortic valve replacement than when the operation is performed in patients without a history of radiotherapy, Milind Y. Desai, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, the Society of Thoracic Surgeons (STS) score isn’t good at risk-stratifying patients with radiation-induced aortic stenosis who are under consideration for surgical aortic valve replacement (SAVR).
Radiation-induced heart disease is a late complication of thoracic radiotherapy. It’s particularly common in patients who got radiation for lymphomas or breast cancer. It can affect any cardiac structure, including the myocardium, pericardium, valves, coronary arteries, and the conduction system.
Aortic stenosis is the most common valvular manifestation, present in roughly 80% of patients with radiation-induced heart disease. At the Cleveland Clinic, the average time from radiotherapy to development of radiation-induced aortic stenosis (RIAS) is about 20 years. The condition is characterized by thickening of the junction between the base of the anterior mitral leaflet and aortic root, known as the aortomitral curtain, Dr. Desai explained.
He presented a retrospective observational cohort study involving 172 patients who underwent SAVR for RIAS and an equal number of SAVR patients with no such history. The groups were matched by age, sex, aortic valve area, and type and timing of SAVR. Of note, the group with RIAS had a mean preoperative STS score of 11, and the control group averaged a similar score of 10.
The key finding: During a mean follow-up of 6 years, the all-cause mortality rate was a hefty 48% in patients with RIAS, compared with just 7% in matched controls. Only about 5% of deaths in the group with RIAS were from recurrent malignancy. The low figure is not surprising given the average 20-year lag between radiotherapy and development of radiation-induced heart disease.
“In our experience, most of these patients develop a recurrent pleural effusion and nasty cardiopulmonary issues that result in their death,” according to Dr. Desai.
In a multivariate Cox proportional hazards analysis, a history of chest radiation therapy was by far the strongest predictor of all-cause mortality, conferring an 8.5-fold increase in risk.
The only other statistically significant predictor of mortality during follow-up in multivariate analysis was a high STS score, with an associated weak albeit statistically significant 1.15-fold increased risk. A total of 30 of 78 (39%) RIAS patients with an STS score below 4 died during follow-up, compared with none of 91 controls.
Thirty-four of 92 (37%) RIAS patients under age 65 died during follow-up, whereas none of 83 control SAVR patients did so.
Having coronary artery bypass surgery or other cardiac surgery at the time of SAVR was not associated with significantly increased risk of mortality compared with solo SAVR.
In-hospital outcomes were consistently worse after SAVR in the RIAS group. Half of the RIAS patients experienced in-hospital atrial fibrillation and 29% developed persistent atrial fibrillation, compared with 30% and 24% of controls. About 22% of RIAS patients were readmitted within 3 months after surgery, as were only 8% of controls. In-hospital mortality occurred in 2% of SAVR patients with RIAS; none of the matched controls did.
Dr. Desai reported having no financial interests relative to this study.
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: All-cause mortality occurred in 48% of 172 patients with radiation-induced severe aortic stenosis during a mean follow-up of 6 years after surgical aortic valve replacement, compared with just 7% of matched controls.
Data source: This was a retrospective observational study involving 172 closely matched pairs of surgical aortic valve replacement patients.
Disclosures: The presenter reported having no financial conflicts of interest regarding this study.
Beta-blockers curb death risk in patients with primary prevention ICD
ROME – Beta-blocker therapy reduces the risks of all-cause mortality as well as cardiac death in patients with a left ventricular ejection fraction below 35% who get an implantable cardioverter-defibrillator for primary prevention, Laurent Fauchier, MD, PhD, reported at the annual congress of the European Society of Cardiology.
Some physicians have recently urged reconsideration of current guidelines recommending routine use of beta-blockers for prevention of cardiovascular events in certain groups of patients with coronary artery disease, including those with chronic heart failure who have received an ICD for primary prevention of sudden death. And indeed it’s true that the now–relatively old randomized trials of ICDs for primary prevention in patients with chronic heart failure don’t provide any real evidence that beta-blockers reduce mortality in this setting. In fact, the guideline recommendation for beta-blockade has been based upon expert opinion. This was the impetus for Dr. Fauchier and coinvestigators to conduct a large retrospective observational study in a contemporary cohort of heart failure patients who received an ICD for primary prevention during a recent 10-year period at the 12 largest centers in France.
Fifteen percent of the 3,975 French ICD recipients did not receive a beta-blocker. They differed from those who did in that they were on average 2 years older, had an absolute 5% lower ejection fraction, and were more likely to also receive cardiac resynchronization therapy. Propensity score matching based on these and 19 other baseline characteristics enabled investigators to assemble a cohort of 541 closely matched patient pairs, explained Dr. Fauchier, professor of cardiology at Francois Rabelais University in Tours, France.
During a mean follow-up of 3.2 years, the risk of all-cause mortality in ICD recipients not on a beta-blocker was 34% higher than in those who were. Moreover, their risk of cardiac death was 50% greater.
In contrast, beta-blocker therapy had no effect on the risks of sudden death or of appropriate or inappropriate shocks.
The finding that beta-blocker therapy doesn’t prevent sudden death in patients with an ICD for primary prevention has not previously been reported. However, it makes sense. The device prevents such events so effectively that a beta-blocker adds nothing further in that regard, according to Dr. Fauchier.
“Beta-blockers should continue to be used widely, as currently recommended, for heart failure in the specific setting of patients with prophylactic ICD implantation. You do not have the benefit for prevention of sudden death, but you still have all the benefit from preventing cardiac death,” the electrophysiologist concluded.
This study was supported by French governmental research grants. Dr. Fauchier reported serving as a consultant to Bayer, Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.
ROME – Beta-blocker therapy reduces the risks of all-cause mortality as well as cardiac death in patients with a left ventricular ejection fraction below 35% who get an implantable cardioverter-defibrillator for primary prevention, Laurent Fauchier, MD, PhD, reported at the annual congress of the European Society of Cardiology.
Some physicians have recently urged reconsideration of current guidelines recommending routine use of beta-blockers for prevention of cardiovascular events in certain groups of patients with coronary artery disease, including those with chronic heart failure who have received an ICD for primary prevention of sudden death. And indeed it’s true that the now–relatively old randomized trials of ICDs for primary prevention in patients with chronic heart failure don’t provide any real evidence that beta-blockers reduce mortality in this setting. In fact, the guideline recommendation for beta-blockade has been based upon expert opinion. This was the impetus for Dr. Fauchier and coinvestigators to conduct a large retrospective observational study in a contemporary cohort of heart failure patients who received an ICD for primary prevention during a recent 10-year period at the 12 largest centers in France.
Fifteen percent of the 3,975 French ICD recipients did not receive a beta-blocker. They differed from those who did in that they were on average 2 years older, had an absolute 5% lower ejection fraction, and were more likely to also receive cardiac resynchronization therapy. Propensity score matching based on these and 19 other baseline characteristics enabled investigators to assemble a cohort of 541 closely matched patient pairs, explained Dr. Fauchier, professor of cardiology at Francois Rabelais University in Tours, France.
During a mean follow-up of 3.2 years, the risk of all-cause mortality in ICD recipients not on a beta-blocker was 34% higher than in those who were. Moreover, their risk of cardiac death was 50% greater.
In contrast, beta-blocker therapy had no effect on the risks of sudden death or of appropriate or inappropriate shocks.
The finding that beta-blocker therapy doesn’t prevent sudden death in patients with an ICD for primary prevention has not previously been reported. However, it makes sense. The device prevents such events so effectively that a beta-blocker adds nothing further in that regard, according to Dr. Fauchier.
“Beta-blockers should continue to be used widely, as currently recommended, for heart failure in the specific setting of patients with prophylactic ICD implantation. You do not have the benefit for prevention of sudden death, but you still have all the benefit from preventing cardiac death,” the electrophysiologist concluded.
This study was supported by French governmental research grants. Dr. Fauchier reported serving as a consultant to Bayer, Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.
ROME – Beta-blocker therapy reduces the risks of all-cause mortality as well as cardiac death in patients with a left ventricular ejection fraction below 35% who get an implantable cardioverter-defibrillator for primary prevention, Laurent Fauchier, MD, PhD, reported at the annual congress of the European Society of Cardiology.
Some physicians have recently urged reconsideration of current guidelines recommending routine use of beta-blockers for prevention of cardiovascular events in certain groups of patients with coronary artery disease, including those with chronic heart failure who have received an ICD for primary prevention of sudden death. And indeed it’s true that the now–relatively old randomized trials of ICDs for primary prevention in patients with chronic heart failure don’t provide any real evidence that beta-blockers reduce mortality in this setting. In fact, the guideline recommendation for beta-blockade has been based upon expert opinion. This was the impetus for Dr. Fauchier and coinvestigators to conduct a large retrospective observational study in a contemporary cohort of heart failure patients who received an ICD for primary prevention during a recent 10-year period at the 12 largest centers in France.
Fifteen percent of the 3,975 French ICD recipients did not receive a beta-blocker. They differed from those who did in that they were on average 2 years older, had an absolute 5% lower ejection fraction, and were more likely to also receive cardiac resynchronization therapy. Propensity score matching based on these and 19 other baseline characteristics enabled investigators to assemble a cohort of 541 closely matched patient pairs, explained Dr. Fauchier, professor of cardiology at Francois Rabelais University in Tours, France.
During a mean follow-up of 3.2 years, the risk of all-cause mortality in ICD recipients not on a beta-blocker was 34% higher than in those who were. Moreover, their risk of cardiac death was 50% greater.
In contrast, beta-blocker therapy had no effect on the risks of sudden death or of appropriate or inappropriate shocks.
The finding that beta-blocker therapy doesn’t prevent sudden death in patients with an ICD for primary prevention has not previously been reported. However, it makes sense. The device prevents such events so effectively that a beta-blocker adds nothing further in that regard, according to Dr. Fauchier.
“Beta-blockers should continue to be used widely, as currently recommended, for heart failure in the specific setting of patients with prophylactic ICD implantation. You do not have the benefit for prevention of sudden death, but you still have all the benefit from preventing cardiac death,” the electrophysiologist concluded.
This study was supported by French governmental research grants. Dr. Fauchier reported serving as a consultant to Bayer, Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: Patients with heart failure with reduced ejection fraction who received an ICD for primary prevention and were not on a beta-blocker were at an adjusted 50% increased risk for cardiac death and 34% increased risk for all-cause mortality during 3.2 years of follow-up, but they were at no increased risk for sudden death.
Data source: A retrospective observational study of all of the nearly 4,000 patients who received a primary prevention ICD at the 12 largest French centers during a recent 10-year period.
Disclosures: This study was supported by French governmental research funds. The presenter reported serving as a consultant to Bayer, Pfizer, Boehringer Ingelheim, Medtronic, and Novartis.
More restrictive hemoglobin threshold recommended for transfusion
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
The two-tiered approach of this important update to the red blood cell transfusion guidelines acknowledges the current state of the evidence and also provides support for making more individualized transfusion decisions.
These new guidelines represent medicine at its best in that they are evidence based, derived from randomized controlled trials, reflect important clinical perspectives, and are definitive for conditions in which data are substantial, but provide greater flexibility for conditions in which data are less certain.
One major limitation of these guidelines is that they are based on hemoglobin level as the transfusion trigger, when good clinical practice dictates that the decision to transfuse should also be based on clinical factors, availability of alternative therapies, and patient preferences.
Mark H. Yazer, MD and Darrell J. Triulzi, MD, are in the division of transfusion medicine at the University of Pittsburgh Medical Center. These comments are adapted from an editorial (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.10887 ). Dr Triulzi reported receiving grants from the National Heart, Lung, and Blood Institute; and receiving personal fees for serving on an advisory board for Fresenius Kabi.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
FROM JAMA
Key clinical point: A restrictive threshold for red blood cell transfusion, in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL, is now recommended for most patients.
Major finding: A more restrictive threshold for red blood cell transfusion is not associated with an increased risk of mortality or other adverse outcomes from transfusion.
Data source: Updated guidelines from the AABB (formerly known as the American Association of Blood Banks).
Disclosures: Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies including CSL and Fresenius Kabi, but no other conflicts of interest were declared.
Midterm results of thoracic stenting for acute type B dissection promising
LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.
Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.
One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).
Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.
Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.
The primary safety endpoint was all-cause mortality within 30 days from the index procedure.
A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.
At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.
One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.
Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.
The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.
LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.
Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.
One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).
Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.
Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.
The primary safety endpoint was all-cause mortality within 30 days from the index procedure.
A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.
At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.
One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.
Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.
The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.
LAS VEGAS – Patients with acute, complicated type B aortic dissections are reported to have a greater than 50% likelihood of dying from their condition. Three-year results of the Valiant thoracic stent graft in the treatment of these dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%, according to Ali Azizzadeh, MD.
Dr. Azizzadeh presented the midterm results of the Medtronic Dissection US IDE trial of endovascular treatment with the Valiant Captivia thoracic stent graft (Medtronic) in acute, complicated type B aortic dissection patients at the 2016 Vascular Interventional Advances meeting.
One-year outcomes of the trial were reported last year in the Annals of Thoracic Surgery (2015 Sep;100:802-9).
Dr. Azizzadeh is a vascular surgeon at the Memorial Hermann Heart and Vascular Institute, Houston.
Between June 2010 and May 2012, 50 patients with acute, complicated type B aortic dissection were enrolled at 16 clinical sites in the United States in this multicenter, prospective, nonrandomized trial with a planned 5-year follow-up.
The primary safety endpoint was all-cause mortality within 30 days from the index procedure.
A total of 28 patients completed their 3-year follow-up. Through 3 years, there were no postindex ruptures or conversions to open surgical repair reported in the trial.
At 3 years, true lumen diameter over the stented region (or endograft segment) remained stable or increased in 92.3% of patients, according to Dr. Azizzadeh. False lumen diameter remained stable or decreased in 69.3% of patients, and the false lumen was partially or completely thrombosed in 75% of patients.
One death (from sepsis) occurred between years 2 and 3; and was adjudicated by the clinical events committee as unrelated to the device, the procedure, or the dissection.
Although these midterm results are encouraging, said Dr. Azizzadeh, longer-term outcomes are needed to assess the durability of the stent graft in this indication.
The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.
AT VIVA16 LAS VEGAS
Key clinical point:
Major finding: Three-year results of the Valiant thoracic stent graft in the treatment of acute type B dissections showed freedom from all-cause mortality of 79.4%, and a freedom from dissection-related mortality of 90%.
Data source: Midterm results were presented from the multicenter, prospective, nonrandomized Medtronic Dissection US IDE trial.
Disclosures: The trial was sponsored by Medtronic. Dr. Azizzadeh has consulted for and received research/trial funding from W.L. Gore & Associates and Medtronic.
Rivaroxaban linked to more bleeding compared with dabigatran in elderly patients with nonvalvular AF
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
This “milestone” study offers real-world data for a large number of older patients with multiple comorbidities who constitute the rising tide of the AF population.
The findings should lead physicians to prescribe dabigatran over rivaroxaban in most patients with AF. Even though this was a retrospective cohort study, there are no prospective randomized trials directly comparing the two non–vitamin-K oral anticoagulants, and the few indirect comparisons derived from clinical trial data are very limited.
Anna L. Parks, MD, is at the University of California, San Francisco. Rita F. Redberg, M.D., is the editor of JAMA Internal Medicine and professor of cardiology at UCSF. Dr. Parks and Dr. Redberg made these remarks in an Editor’s Note accompanying Dr. Graham’s report (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.6429).
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.
This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.
During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.
The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.
The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).
In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).
Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.
Key clinical point: Rivaroxaban is associated with significantly more intra- and extracranial bleeding than dabigatran in patients aged 75 and older with nonvalvular atrial fibrillation.
Major finding: Rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment.
Data source: A retrospective cohort study of 118,891 patients aged 65 and older who initiated anticoagulation therapy for AF during a 2.5-year period.
Disclosures: This study was conducted by employees or contractors of the Centers for Medicare & Medicaid Services and the Food and Drug Administration. Dr. Graham and his associates reported having no relevant financial disclosures.
Genes that drive glucose levels also drive heart disease
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
AT EASD 2016
Key clinical point: Twelve newly identified genes associated with glucose levels appear to be independent drivers of coronary heart disease.
Major finding: Altogether, the constellation of genes raises the risk of heart disease by 43% for every 1 mmol/L increase in blood glucose.
Data source: Analysis of 133,000 subjects without diabetes.
Disclosures: Dr. Merino had no financial disclosures.
Heart failure risk with individual NSAIDs examined in study
Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.
Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).
The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.
Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.
In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.
“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.
The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.
The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.
This report provides additional weight backing the association between increased risk of heart failure with NSAID use and gives better insight on the dose-response relationship between individual NSAIDs and heart failure. However, beyond that, its clinical impact is hurt by the lack of data on the magnitude of excess absolute risk of heart failure with NSAID use, which varies according to baseline cardiovascular risk.
Even though the risk of heart failure associated with NSAID use in the study occurred independent of a history of heart failure, it still is prudent to restrict NSAID use in patients with heart failure because of the high risk noted in this group in other studies.
The widespread use and ease of access to NSAIDs fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone, and this warrants a more restrictive policy by regulatory authorities on the availability of NSAIDs and requirements for health care professionals providing advice on their use.
Gunnar H. Gislason, MD, PhD, is a professor of cardiology at Copenhagen University Hospital Herlev and Gentofte, Denmark, and Christian Torp-Pedersen, MD, is a professor of cardiology at Aalborg (Denmark) University. Dr. Gislason had no disclosures and Dr. Torp-Pedersen advises Bayer on anticoagulation for atrial fibrillation. Their remarks are taken from an editorial accompanying the study by Mr. Arfè and his colleagues (BMJ. 2016 Sep;354:i5163 doi: 10.1136/bmj.i5163).
This report provides additional weight backing the association between increased risk of heart failure with NSAID use and gives better insight on the dose-response relationship between individual NSAIDs and heart failure. However, beyond that, its clinical impact is hurt by the lack of data on the magnitude of excess absolute risk of heart failure with NSAID use, which varies according to baseline cardiovascular risk.
Even though the risk of heart failure associated with NSAID use in the study occurred independent of a history of heart failure, it still is prudent to restrict NSAID use in patients with heart failure because of the high risk noted in this group in other studies.
The widespread use and ease of access to NSAIDs fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone, and this warrants a more restrictive policy by regulatory authorities on the availability of NSAIDs and requirements for health care professionals providing advice on their use.
Gunnar H. Gislason, MD, PhD, is a professor of cardiology at Copenhagen University Hospital Herlev and Gentofte, Denmark, and Christian Torp-Pedersen, MD, is a professor of cardiology at Aalborg (Denmark) University. Dr. Gislason had no disclosures and Dr. Torp-Pedersen advises Bayer on anticoagulation for atrial fibrillation. Their remarks are taken from an editorial accompanying the study by Mr. Arfè and his colleagues (BMJ. 2016 Sep;354:i5163 doi: 10.1136/bmj.i5163).
This report provides additional weight backing the association between increased risk of heart failure with NSAID use and gives better insight on the dose-response relationship between individual NSAIDs and heart failure. However, beyond that, its clinical impact is hurt by the lack of data on the magnitude of excess absolute risk of heart failure with NSAID use, which varies according to baseline cardiovascular risk.
Even though the risk of heart failure associated with NSAID use in the study occurred independent of a history of heart failure, it still is prudent to restrict NSAID use in patients with heart failure because of the high risk noted in this group in other studies.
The widespread use and ease of access to NSAIDs fuels the common misconception that NSAIDs are harmless drugs that are safe for everyone, and this warrants a more restrictive policy by regulatory authorities on the availability of NSAIDs and requirements for health care professionals providing advice on their use.
Gunnar H. Gislason, MD, PhD, is a professor of cardiology at Copenhagen University Hospital Herlev and Gentofte, Denmark, and Christian Torp-Pedersen, MD, is a professor of cardiology at Aalborg (Denmark) University. Dr. Gislason had no disclosures and Dr. Torp-Pedersen advises Bayer on anticoagulation for atrial fibrillation. Their remarks are taken from an editorial accompanying the study by Mr. Arfè and his colleagues (BMJ. 2016 Sep;354:i5163 doi: 10.1136/bmj.i5163).
Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.
Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).
The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.
Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.
In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.
“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.
The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.
The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.
Nine popular painkillers – including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors – are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ.
Although data from previous large studies suggest that high doses of NSAIDs as well as COX-2 inhibitors increase the risk of hospital admission for heart failure, “there is still limited information on the risk of heart failure associated with the use of individual NSAIDs in clinical practice,” wrote Andrea Arfè of the University of Milano-Bicocca, Milan, and his colleagues (BMJ. 2016 Sep;354:i4857 doi: 10.1136/bmj.i4857).
The researchers reviewed data from five electronic health databases in the Netherlands, Italy, Germany, and the United Kingdom as part of the SOS (Safety of Non-Steroidal Anti-Inflammatory Drugs) project and conducted a nested, case-control study including 92,163 hospital admissions for heart failure and 8,246,403 controls matched for age, sex, and year of study entry. The study included 23 traditional NSAIDs and four selective COX-2 inhibitors.
Overall, individual use of any of nine different NSAIDs within 14 days was associated with a nearly 20% higher likelihood of hospital admission for heart failure, compared with NSAID use more than 183 days in the past (odds ratio, 1.19). For seven traditional NSAIDS (diclofenac, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, and piroxicam) and the COX-2 inhibitors etoricoxib and rofecoxib, the odds ratios for heart failure with current use ranged from 1.16 for naproxen to 1.83 for ketorolac, compared with past use.
In addition, the odds of hospitalization for heart failure doubled for diclofenac, etoricoxib, indomethacin, piroxicam, and rofecoxib when dosed at two or more daily dose equivalents, the researchers noted. There was no increase in the odds of hospitalization for heart failure with celecoxib when dosed at standard levels, but “indomethacin and etoricoxib seemed to increase the risk of hospital admission for heart failure, even if used at medium doses,” they said. Other lesser-used NSAIDs were associated with an increased risk, but it was not statistically significant.
“The effect of individual NSAIDs could depend on a complex interaction of pharmacological properties, including duration and extent of platelet inhibition, extent of blood pressure increase, and properties possibly unique to the molecule,” the researchers said.
The findings were limited by several factors including misclassification of outcomes and the observational nature of the study, which prevents conclusions about cause and effect, the researchers noted. However, “Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinical practice and regulatory activities,” they said.
The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.
FROM BMJ
Key clinical point: Patients taking high doses of certain NSAIDS had significantly higher odds of hospital admission for heart failure, compared with controls not currently taking the medications.
Major finding: The odds of hospitalization for heart failure increased by 19% overall for adults currently using certain NSAIDS and doubled for users of certain NSAIDs at high doses.
Data source: The data come from approximately 10 million hospital admissions taken from databases in the Netherlands, Italy, Germany, and the United Kingdom.
Disclosures: The study was funded in part by the European Community’s seventh Framework Programme. Mr. Arfè had no financial conflicts to disclose. Several study coauthors disclosed relationships with multiple companies including AstraZeneca, Bayer, Celgene, GlaxoSmithKline, Schwabe, and Novartis.
