Benefits of Ramipril in High Cardiovascular Risk Patients: The HOPE Trial
Ramipril significantly reduces cardiovascular mortality (37%), myocardial infarction (22%), and stroke (33%) in high-risk patients, with a 25% reduction in the combined primary outcome of these events, as demonstrated conclusively in the HOPE trial. 1
Key Findings from the HOPE Trial
The Heart Outcomes Prevention Evaluation (HOPE) trial was a landmark study that evaluated the effect of ramipril 10 mg daily in patients at high risk for cardiovascular events:
- Study Population: 9,541 patients (age ≥55 years) with evidence of vascular disease or diabetes plus one additional cardiovascular risk factor, but without heart failure 1, 2
- Primary Outcome: Composite of cardiovascular death, myocardial infarction, and stroke
- Results: Each component of the primary outcome showed statistically significant reductions:
- 37% reduction in cardiovascular death (P<0.0001)
- 22% reduction in myocardial infarction (P<0.01)
- 33% reduction in stroke (P<0.0074)
- 25% reduction in combined primary outcome (P<0.0004) 1
Benefits Beyond Blood Pressure Reduction
The cardiovascular benefits of ramipril in the HOPE trial extended beyond what would be expected from its modest blood pressure-lowering effect:
- Mean blood pressure reduction was only 2-3 mmHg systolic and 1-2 mmHg diastolic 1, 3
- Benefits were observed in both hypertensive and normotensive patients 1
- A HOPE substudy revealed that 24-hour ambulatory blood pressure monitoring showed greater reductions than office measurements, suggesting the trial may have underestimated the blood pressure effect 1
Additional Benefits in Diabetic Patients
The HOPE study included a substantial diabetic population (3,577 patients, 37.5% of total) with remarkable findings:
- Significant reduction in diabetic complications (composite of nephropathy, need for dialysis, and diabetic retinopathy) 1
- 24% reduction in overt nephropathy (P=0.027) 1
- Reduced incidence of new diabetes diagnosis among non-diabetic participants 1
- The MICRO-HOPE substudy confirmed cardiorenal benefits in diabetic patients 1
Other Clinical Benefits
Ramipril therapy in the HOPE trial also demonstrated significant reductions in:
- All-cause mortality (16% reduction, P=0.005) 2
- Revascularization procedures (15% reduction, P<0.001) 2
- Cardiac arrest (38% reduction, P=0.02) 2
- Heart failure (23% reduction, P<0.001) 2
- Diabetes-related complications (16% reduction, P=0.03) 2
Clinical Implications and Guidelines
Based on the HOPE trial results, the ACC/AHA guidelines recommend:
- Class I recommendation (Level of Evidence: A): ACE inhibitors for all patients with coronary artery disease who also have diabetes and/or left ventricular systolic dysfunction 1
- Class IIa recommendation (Level of Evidence: B): ACE inhibitors for patients with CAD or other vascular disease without these specific conditions 1
Important Considerations and Caveats
- Renal function: Monitor renal function in patients starting ramipril, particularly those with pre-existing renal conditions; use with caution in patients with eGFR <30 mL/min/1.73 m² 4
- Dose matters: The HOPE trial used ramipril 10 mg daily, which should be the target dose when possible 2
- Patient selection: The benefits may be more pronounced in higher-risk patients; the PEACE trial with lower-risk patients showed less benefit with trandolapril 1
- Long-term therapy: Benefits were demonstrated over a mean follow-up of 5 years, suggesting the importance of sustained therapy 3, 2
The HOPE trial provides compelling evidence that ramipril should be considered for all patients with established cardiovascular disease or diabetes with additional risk factors, regardless of blood pressure status, to reduce cardiovascular morbidity and mortality.