Benefits of Ramipril in High Cardiovascular Risk Patients: The HOPE Trial
Ramipril significantly reduces cardiovascular mortality by 37%, myocardial infarction by 22%, stroke by 33%, and the combined primary outcome by 25% in high-risk patients, as demonstrated in the landmark HOPE trial. 1
Key Findings from the HOPE Trial
The Heart Outcomes Prevention Evaluation (HOPE) trial was a large, multinational randomized controlled trial that evaluated the efficacy of ramipril in high-risk patients:
- Study Population: 9,297 high-risk patients (≥55 years) with evidence of vascular disease or diabetes plus one additional cardiovascular risk factor, without known left ventricular dysfunction or heart failure 2
- Intervention: Ramipril 10 mg once daily versus placebo
- Follow-up: Mean of 5 years
- Primary Outcome: Composite of myocardial infarction, stroke, or death from cardiovascular causes
Major Outcome Reductions with Ramipril
| Outcome | Reduction |
|---|---|
| Cardiovascular mortality | 37% |
| Myocardial infarction | 22% |
| Stroke | 33% |
| Combined primary outcome | 25% |
| All-cause mortality | 16% |
| Heart failure | 23% |
| Diabetic complications (including nephropathy) | 24% |
Benefits Beyond Blood Pressure Reduction
A critical finding of the HOPE trial was that the benefits of ramipril extended beyond its modest blood pressure-lowering effect:
- The reduction in blood pressure attributable to ramipril was only 3-4 mmHg systolic and 1-2 mmHg diastolic 3
- The blood pressure lowering effect accounts for only a small part (2-3 mmHg reduction) of ramipril's overall benefit 1
- Multiple regression analysis showed similar risk reductions even after adjusting for the effects of blood pressure reduction 3
Benefits in Special Populations
Diabetic Patients
- The 3,577 diabetic subjects in the HOPE trial showed even more striking benefits, with a 25% reduction in the combined primary endpoint 3
- Ramipril reduced diabetic complications, including nephropathy, need for dialysis, and diabetic retinopathy 1
- Decreased the development of new diabetes in previously non-diabetic patients 1, 4
Normotensive vs. Hypertensive Patients
- Benefits were observed in both hypertensive and normotensive patients 1
- The HOPE study demonstrated that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors 3
Clinical Implications
The HOPE trial significantly expanded the indications for ACE inhibitors beyond traditional uses in heart failure, left ventricular dysfunction, and hypertension to include:
- Patients with established coronary artery disease
- Diabetic patients with additional risk factors
- Patients with other vascular diseases (peripheral arterial disease, stroke)
The American College of Cardiology recommends:
- ACE inhibitors for all patients with coronary artery disease who also have diabetes and/or left ventricular systolic dysfunction (Class I Recommendation, Level of Evidence: A) 1
- ACE inhibitors for patients with coronary artery disease or other vascular disease without diabetes or LV dysfunction (Class IIa Recommendation, Level of Evidence: B) 1
Safety Considerations
- Renal function should be monitored in patients starting ramipril, particularly those with pre-existing renal conditions 1
- Use with caution in patients with eGFR <30 mL/min/1.73 m² 1
- Symptomatic postural hypotension is infrequent but can occur in patients who are salt- and/or volume-depleted 5
Mechanism of Action
The benefits of ramipril beyond blood pressure reduction may be attributed to:
- Reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation
- Possible plaque stabilization 3
- Improvement in endothelial function
- Anti-inflammatory effects
The HOPE trial provided compelling evidence that ramipril significantly reduces cardiovascular events in high-risk patients, establishing ACE inhibitors as a cornerstone therapy for cardiovascular risk reduction beyond their traditional role in hypertension and heart failure management.