Background

Angiotensin-converting enzyme (ACE) inhibitors have been proven to reduce morbidity and mortality in patients with low ejection fraction with and without heart failure. However, there are no data on the impact of ACE inhibitors in patients without pre-existing heart failure, low ejection fraction or hypertension.

Aim

To assess the potential of ramipril to prevent the development of heart failure in patients at high risk of cardiovascular events but without heart failure or known low left ventricular ejection fraction.

Patient characteristics

9297 patients (> 55 years of age) with a history of

• Coronary artery disease, or
• Stroke, or
• Peripheral vascular disease, or
• Diabetes plus one other cardiovascular risk factor (hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level, cigarette smoking, or microalbuminuria).
  

Exclusion criteria

Patients with history of 6 months

• Heart failure, or
• Low left ventricular ejection He fraction < 0.40, or
• On ACE inhibitor treatment, or
• Uncontrolled hypertension or
• Overt nephropathy, or
• Myocardial infarction or stroke within 4 weeks before entering the study.

Treatment groups Study duration

Ramipril (10 mg daily) vs. Placebo 4.5 years

Study outcomes

Primary outcome: A composite of myocardial infarction, stroke and death from cardiovascular causes.
Secondary outcome: Hospitalization for heart failure. (All heart failure was defined as heart failure causing death, heart failure requiring hospitalization, heart failure requiring open-label ACE inhibition, or development of typical symptoms and signs)

Results

1. The rate of developing heart failure was significantly increased as per the following conditions:

2. Ramipril significantly reduced the rate of all heart failure by 23%.

3. Ramipril reduced the incidence of combined cardiovascular death and all heart failure by 24%

4. Ramipril showed significant benefits even in the sub group of patients with normal left ventricular ejection fraction (n=4775).

5. Ramipril also significantly reduced the rate of heart failure by 22% in the much larger group of patients (n=8315) who did not have myocardial infarction.

Conclusion

Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events. HOPE substudy with ramipril extends the benefits of ACE inhibition to an even broader range of patients at high risk of cardiovascular events but without a history of heart failure or known left ventricular ejection fraction <0.40, and undergoing concomitant medical therapy.

Circulation 2003; 107:1284-1290

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