Angiotensin-converting enzyme (ACE) inhibitors have proven benefits in the treatment of chronic heart failure caused by systolic dysfunction. However, it is not known whether these medications can prevent the development of heart failure. Arnold and colleagues report findings from the Heart Outcomes Prevention Evaluation (HOPE) trial to help answer this question. Previous reports from the HOPE trial showed that the ACE inhibitor ramipril reduced rates of myocardial infarction, stroke, and cardiovascular death in patients at high risk for these outcomes.
The HOPE study was a randomized, double-blinded, placebo-controlled trial comparing ramipril and vitamin E in patients at high risk for cardiovascular events. Elevated risk was defined as a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes plus one other risk factor, such as hypertension, elevated total cholesterol level, low high-density lipoprotein level, smoking, or microalbuminuria. Patients with known heart failure were excluded from this group. Heart failure occurred in 10.2 percent of randomized patients during follow-up (median, 4.6 years), and development of heart failure was associated with a fourfold increase in mortality. Patients who had a myocardial infarction during the study had a ninefold increased risk of heart failure. Age was the greatest predictor of developing heart failure. Other significant indicators included higher body mass index, systolic blood pressure, heart rate, and pulse pressure. Including patients with undiagnosed systolic dysfunction in the study group did not affect the findings significantly.
Ramipril use reduced the relative rate of heart failure development by 23 percent and the combined rate of heart failure and cardiovascular death by 24 percent. There was a 13 percent relative reduction in the rate of heart failure in patients who had a myocardial infarction during the study period. To prevent one new case of heart failure, 40 high-risk patients would have to be treated for 4.5 years. However, when heart failure was combined with other key outcomes of the HOPE trial (i.e., myocardial infarction, cardiovascular death, stroke, revascularization), only 13 patients would need to be treated to prevent one outcome.
The authors conclude that the beneficial effects of ACE inhibitors can be extended to the prevention of heart failure in patients at high risk for cardiovascular events.