Efficacy of Perindopril in Reducing Risk of Cardiac Events
Efficacy of Perindopril in Reducing Risk of Cardiac Events
Background: The aim of the study was to assess the effect on cardiac events of adding perindopril 8 mg once daily to standard preventive therapy in the subgroup of EUROPA patients with previous revascularization and without previous myocardial infarction (MI).
Methods: We conducted a subgroup analysis of the EUROPA study patients according to their revascularization and previous MI history. Among the 12218 patients of EUROPA, we identified 6709 (54.9%) patients who had a previous revascularization. Approximately equal proportions had undergone percutaneous coronary intervention (3122) or coronary artery bypass grafting (3136). Of the revascularized patients, 3047 (24.9%) patients had not experienced a previous MI.
Results: Out of the 6709 revascularized patients, 3340 were treated with perindopril and 3369 with placebo. Baseline characteristics were similar to the whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood pressure), and medications at screening. The mean patient age was 60 years, and 85% were men. The relative risk reduction with perindopril 8 mg was 17.3% (95% CI 1.3%-30.8%, P = .035) for the composite primary end point of cardiovascular death, nonfatal MI, and resuscitated cardiac arrest and was 23% (95% CI 4.9%-37.6%, P = .015) for fatal and nonfatal MI. In the 3047 revascularized patients without a history of MI, perindopril was associated with a relative risk reduction of 31.7% for fatal and nonfatal MI (95% CI 4.4%-51.2%, P = .026).
Conclusion: Perindopril 8 mg daily is beneficial for primary and secondary prevention of cardiac events in patients with coronary artery disease without clinical evidence of heart failure including those with previous revascularization.
Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are widely used to relieve symptoms and improve prognosis in patients with stable angina. However, there is a lack of consensus about the appropriate long-term medical therapy (ie, after the immediate postoperative period) for patients who have undergone these procedures. A recent article pointed out the inadequacy of evidence concerning the efficacy of cardiac medical therapy in patients who have undergone CABG. However, patients with established coronary artery disease (CAD) represent a group in which secondary cardiovascular disease prevention is likely to be particularly useful and cost-effective.
Existing guidelines do provide some recommendations. The American College of Cardiology/American Heart Association (ACC/AHA) 2001 guidelines for PCI suggest that post-PCI patients should adhere to recommended medical therapies known to reduce subsequent morbidity and mortality from CAD; and more recent ACC/AHA guidelines on CABG recommend the use of antiplatelet agents and lipid-lowering therapy to reduce late morbidity and mortality.
Trials such as SOLVD, SAVE, AIRE, and TRACE established that angiotensin-converting enzyme (ACE) inhibitors improve the long-term prognosis in patients with reduced left ventricular (LV) ejection fraction. More recently, the HOPE and EUROPA trial results have shown that ACE inhibitors are also useful in patients with normal ejection fraction. The study populations in these 2 trials included patients who had undergone revascularization. However, only one small randomized controlled trial in 149 patients, QUO VADIS, has specifically examined the use of an ACE inhibitor in post-CABG patients with normal LV function. In this trial, fewer patients treated with quinapril (4%) had experienced clinical ischemic events at 1-year follow-up relative to placebo (15%, P = .02). A beneficial effect was also shown with ramipril, which reduced cardiovascular events in postrevascularization patients in APRES; but these patients (n = 159) had moderately reduced LV function. Importantly, only 38% and 30% of patients in QUO VADIS and APRES, respectively, were taking lipid-lowering drugs at baseline.
On the basis of this evidence, it is suggested that ACE inhibitors should routinely be given to patients who have undergone CABG. Furthermore, the ACC/AHA guidelines for preventing myocardial infarction (MI) and death in patients with atherosclerotic cardiovascular disease suggest that ACE inhibitors be considered for all patients with vascular disease. However, the QUIET and PEACE studies, which included high proportions of revascularized patients (100% and 72%, respectively), did not show reductions in their primary end points (composites of ischemic cardiac events) after treatment with quinapril and trandolapril. Therefore, further clear evidence of the benefits of ACE inhibitors in postrevascularization patients would be useful. Consequently, we conducted a subanalysis of the EUROPA study to examine the effect on the rate of cardiac events of adding perindopril 8 mg once daily to standard therapy in CAD patients with previous revascularization.
Abstract and Introduction
Abstract
Background: The aim of the study was to assess the effect on cardiac events of adding perindopril 8 mg once daily to standard preventive therapy in the subgroup of EUROPA patients with previous revascularization and without previous myocardial infarction (MI).
Methods: We conducted a subgroup analysis of the EUROPA study patients according to their revascularization and previous MI history. Among the 12218 patients of EUROPA, we identified 6709 (54.9%) patients who had a previous revascularization. Approximately equal proportions had undergone percutaneous coronary intervention (3122) or coronary artery bypass grafting (3136). Of the revascularized patients, 3047 (24.9%) patients had not experienced a previous MI.
Results: Out of the 6709 revascularized patients, 3340 were treated with perindopril and 3369 with placebo. Baseline characteristics were similar to the whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood pressure), and medications at screening. The mean patient age was 60 years, and 85% were men. The relative risk reduction with perindopril 8 mg was 17.3% (95% CI 1.3%-30.8%, P = .035) for the composite primary end point of cardiovascular death, nonfatal MI, and resuscitated cardiac arrest and was 23% (95% CI 4.9%-37.6%, P = .015) for fatal and nonfatal MI. In the 3047 revascularized patients without a history of MI, perindopril was associated with a relative risk reduction of 31.7% for fatal and nonfatal MI (95% CI 4.4%-51.2%, P = .026).
Conclusion: Perindopril 8 mg daily is beneficial for primary and secondary prevention of cardiac events in patients with coronary artery disease without clinical evidence of heart failure including those with previous revascularization.
Introduction
Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are widely used to relieve symptoms and improve prognosis in patients with stable angina. However, there is a lack of consensus about the appropriate long-term medical therapy (ie, after the immediate postoperative period) for patients who have undergone these procedures. A recent article pointed out the inadequacy of evidence concerning the efficacy of cardiac medical therapy in patients who have undergone CABG. However, patients with established coronary artery disease (CAD) represent a group in which secondary cardiovascular disease prevention is likely to be particularly useful and cost-effective.
Existing guidelines do provide some recommendations. The American College of Cardiology/American Heart Association (ACC/AHA) 2001 guidelines for PCI suggest that post-PCI patients should adhere to recommended medical therapies known to reduce subsequent morbidity and mortality from CAD; and more recent ACC/AHA guidelines on CABG recommend the use of antiplatelet agents and lipid-lowering therapy to reduce late morbidity and mortality.
Trials such as SOLVD, SAVE, AIRE, and TRACE established that angiotensin-converting enzyme (ACE) inhibitors improve the long-term prognosis in patients with reduced left ventricular (LV) ejection fraction. More recently, the HOPE and EUROPA trial results have shown that ACE inhibitors are also useful in patients with normal ejection fraction. The study populations in these 2 trials included patients who had undergone revascularization. However, only one small randomized controlled trial in 149 patients, QUO VADIS, has specifically examined the use of an ACE inhibitor in post-CABG patients with normal LV function. In this trial, fewer patients treated with quinapril (4%) had experienced clinical ischemic events at 1-year follow-up relative to placebo (15%, P = .02). A beneficial effect was also shown with ramipril, which reduced cardiovascular events in postrevascularization patients in APRES; but these patients (n = 159) had moderately reduced LV function. Importantly, only 38% and 30% of patients in QUO VADIS and APRES, respectively, were taking lipid-lowering drugs at baseline.
On the basis of this evidence, it is suggested that ACE inhibitors should routinely be given to patients who have undergone CABG. Furthermore, the ACC/AHA guidelines for preventing myocardial infarction (MI) and death in patients with atherosclerotic cardiovascular disease suggest that ACE inhibitors be considered for all patients with vascular disease. However, the QUIET and PEACE studies, which included high proportions of revascularized patients (100% and 72%, respectively), did not show reductions in their primary end points (composites of ischemic cardiac events) after treatment with quinapril and trandolapril. Therefore, further clear evidence of the benefits of ACE inhibitors in postrevascularization patients would be useful. Consequently, we conducted a subanalysis of the EUROPA study to examine the effect on the rate of cardiac events of adding perindopril 8 mg once daily to standard therapy in CAD patients with previous revascularization.
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