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    • HOPE

    "Ramipril in High-Risk Patients".The New England Journal of Medicine. 2000. 342(3):145-153. PubMed • Full text • PDF

    Clinical Question


    Does ramipril reduce the risk of cardiovascular events in high-risk patients without heart failure or left ventricular dysfunction?

    Bottom Line


    In high-risk patients without heart failure or left ventricular dysfunction, ramipril significantly reduces the rates of death, myocardial infarction, stroke, coronary revascularization, cardiac arrest, and heart failure, as well as the risk of complications related to diabetes and the incidence of new diabetes cases.

    Major Points




    Guidelines


    As of the last knowledge update, guidelines recommend the use of ACE inhibitors in patients with established cardiovascular disease for risk reduction, regardless of left ventricular function or presence of heart failure.

    Design


    Multicenter, double-blind, two-by-two factorial, randomized, placebo-controlled trial.

    Population


    - Inclusion Criteria: Men and women 55 years or older with evidence of vascular disease or diabetes, plus at least one cardiovascular risk factor, and no known low ejection fraction or heart failure.
    - Baseline Characteristics: Age ≥55, 2480 women, 5128 ≥65 years old, 8162 with cardiovascular disease, 4355 with hypertension, 3577 with diabetes.

    Interventions


    - Ramipril (10 mg once per day) vs. matching placebo.
    - Mean follow-up of 5 years.

    Outcomes


    - Primary Outcome: A composite of myocardial infarction, stroke, or death from cardiovascular causes.
    - Secondary Outcomes: Death from any cause, revascularization procedures, hospitalization for unstable angina or heart failure, complications related to diabetes, worsening angina, cardiac arrest, heart failure, and development of diabetes.

    Major Points


    - Ramipril group had significantly fewer primary outcome events (14.0%) compared to the placebo group (17.8%; relative risk 0.78).
    - Significant reductions in individual components of the primary endpoint and secondary outcomes were observed for ramipril versus placebo.
    - Ramipril reduced the incidence of complications related to diabetes and new cases of diabetes.

    Criticisms


    - The significances of small blood pressure changes cannot be discounted as a contributing factor to the overall outcome.
    - The overall generalizability to other populations was not explored within the scope of this study.

    Funding


    Medical Research Council of Canada, Hoechst–Marion Roussel, AstraZeneca, King Pharmaceuticals, Natural Source Vitamin E Association and Negma, Heart and Stroke Foundation of Ontario, and other organizations.

    Further Reading