Should Patients With Stable Coronary Artery Disease Be Treated
Should Patients With Stable Coronary Artery Disease Be Treated
Original article The PEACE trial investigators (2004) Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease. N Engl J Med 351: 2058-2068
Studies have shown that angiotensin-converting-enzyme (ACE) inhibitors can successfully reduce cardiovascular-related mortality and myocardial infarction (MI) in high-risk patients with heart failure, left-ventricular dysfunction and coronary disease. Whether ACE inhibitors, in addition to conventional therapy, benefit patients at low risk is unknown.
Whether cardiovascular-related mortality, nonfatal MI or revascularization are reduced when patients with stable coronary artery disease, with or without marginally reduced left-ventricular systolic function, are treated with ACE inhibitors.
The 4-year, international, randomized, placebo-controlled Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial included patients aged at least 50 years old with normal left-ventricular function or a left-ventricular ejection fraction of 0.4 or more. In addition, eligible patients had either undergone revascularization, experienced MI 3 months or more before trial entry or had stenosis of at least 50% in one or more native vessel, identified by angiography. Patients were excluded if they were hospitalized for unstable angina within 2 months of trial entry, they were taking angiotensin-II-receptor blockers or ACE inhibitors or had undergone revascularization within 3 months of trial entry. Other exclusion criteria included valvular heart disease requiring an operation, serum potassium and creatinine levels higher than 5.5 mM/l and 2.0 mg/dl, respectively, and proposed coronary revascularization procedures.
Initially, all patients received 2 mg trandolapril daily for 2 weeks. Patients experiencing side effects, not adhering to the regimen or experiencing large serum potassium or creatinine increases were excluded. If still eligible, patients were randomized to 2 mg trandolapril or placebo daily. If tolerated, trandolapril was increased to 4 mg daily at 6 months. Patients were followed-up every 6 months thereafter.
The main endpoint was nonfatal MI or cardiovascular-related mortality, modified to include coronary revascularization during the trial. The secondary endpoint was a combination of nonfatal MI, cardiovascular-related mortality or revascularization.
In total, 8,290 patients were included, 4,158 patients received trandolapril and 4,132 placebo (mean age 64 years, 72% had undergone previous revascularization, 70% were receiving lipid-lowering therapy in the two groups and 81% and 83% respectively were male). The mean blood pressure of the trandolapril group patients dropped significantly more than in the placebo group after 36 months. ACE inhibitor therapy did not, however, reduce the occurrence of nonfatal MI, cardiovascular-related deaths or revascularization when compared with placebo (21.9% in trandolapril-treated vs 22.5% in placebo-treated patients, P = 0.43). ACE inhibitor therapy did not confer any advantage in terms of the composite secondary endpoint of nonfatal MI, cardiovascular-related death or coronary revascularization.
Patients at low risk of cardiovascular events (i.e. stable coronary artery disease and normal or slightly impaired left-ventricular function) do not benefit from ACE inhibitor therapy.
Original article The PEACE trial investigators (2004) Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease. N Engl J Med 351: 2058-2068
Studies have shown that angiotensin-converting-enzyme (ACE) inhibitors can successfully reduce cardiovascular-related mortality and myocardial infarction (MI) in high-risk patients with heart failure, left-ventricular dysfunction and coronary disease. Whether ACE inhibitors, in addition to conventional therapy, benefit patients at low risk is unknown.
Whether cardiovascular-related mortality, nonfatal MI or revascularization are reduced when patients with stable coronary artery disease, with or without marginally reduced left-ventricular systolic function, are treated with ACE inhibitors.
The 4-year, international, randomized, placebo-controlled Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial included patients aged at least 50 years old with normal left-ventricular function or a left-ventricular ejection fraction of 0.4 or more. In addition, eligible patients had either undergone revascularization, experienced MI 3 months or more before trial entry or had stenosis of at least 50% in one or more native vessel, identified by angiography. Patients were excluded if they were hospitalized for unstable angina within 2 months of trial entry, they were taking angiotensin-II-receptor blockers or ACE inhibitors or had undergone revascularization within 3 months of trial entry. Other exclusion criteria included valvular heart disease requiring an operation, serum potassium and creatinine levels higher than 5.5 mM/l and 2.0 mg/dl, respectively, and proposed coronary revascularization procedures.
Initially, all patients received 2 mg trandolapril daily for 2 weeks. Patients experiencing side effects, not adhering to the regimen or experiencing large serum potassium or creatinine increases were excluded. If still eligible, patients were randomized to 2 mg trandolapril or placebo daily. If tolerated, trandolapril was increased to 4 mg daily at 6 months. Patients were followed-up every 6 months thereafter.
The main endpoint was nonfatal MI or cardiovascular-related mortality, modified to include coronary revascularization during the trial. The secondary endpoint was a combination of nonfatal MI, cardiovascular-related mortality or revascularization.
In total, 8,290 patients were included, 4,158 patients received trandolapril and 4,132 placebo (mean age 64 years, 72% had undergone previous revascularization, 70% were receiving lipid-lowering therapy in the two groups and 81% and 83% respectively were male). The mean blood pressure of the trandolapril group patients dropped significantly more than in the placebo group after 36 months. ACE inhibitor therapy did not, however, reduce the occurrence of nonfatal MI, cardiovascular-related deaths or revascularization when compared with placebo (21.9% in trandolapril-treated vs 22.5% in placebo-treated patients, P = 0.43). ACE inhibitor therapy did not confer any advantage in terms of the composite secondary endpoint of nonfatal MI, cardiovascular-related death or coronary revascularization.
Patients at low risk of cardiovascular events (i.e. stable coronary artery disease and normal or slightly impaired left-ventricular function) do not benefit from ACE inhibitor therapy.