Cardiovascular disease: ramipril reduced death and cardiovascular disease in high-risk patients

Clinical bottom line (level 1b)

  1. Patients at high-risk for cardiovascular disease who took ramipril compared with placebo were less likely to die (NNT = 55 at 5 years) , have a myocardial infarction (NNT = 44 at 5 years) , a stroke (NNT = at 68 years) , or develop heart failure (NNT = 39 at 5 years) .
  2. Patients on ramipril were less likely to develop worsening angina (NNT = 41 at 5 years) , require revascularisation (NNT = 38 at 5 years) or have a cardiac arrest (NNT = 222 at 5 years) .
  3. Patients on ramipril were less likely to develop diabetes (NNT = 61 at 5 years) or have diabetic complications (NNT = 85 at 5 years) .
  4. Patients on ramipril were more likely to discontinue treatment permanently (NNH = 52 at 5 years) , particularly due to cough (NNH = 18 at 5 years) .
The Heart Outcomes Prevention Evaluation Study Investigators : New England Journal of Medicine 2000; 334: -
Expires November 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 267 acute hospitals in the Americas and Europe

9297 patients (aged mean 66, 73% male) with a history of coronary artery disease, stroke, peripheral vascular disease or diabetes plus one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low high-density lipoprotein cholesterol levels, cigarette smoking or documented microalbuminuria)

Excluded if
  • aged < 55
  • non-compliance (< 80% of pills taken), side-effects or abnormal serum creatinine or potassium levels
  • heart failure
  • ejection fraction < 40%
  • taking ACE inhibitor or vitamin E
  • uncontrolled hypertension or overt nephropathy
  • stroke or myocardial infarction within previous 4 weeks


    • Note:
  • 56% had an echocardiogram - only 8.2% of these patients had low ejection fraction.


    • Control Group: (n = 4652, 4652 analysed): placebo
    Experimental Group: (n = 4645, 4645 analysed): ramipril 2.5 mg for one week, 5 mg for 3 weeks, then 10 mg daily
    Patients were also randomised to 400 IU vitamin E daily
    99.9% followed for 5 years

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death from any cause 5 years 568
    (12.2%)    		 482
    (10.4%)    		 15%
    (5% to 24%)    		 1.83%
    (0.55% to 3.12%)    		 55
    (32 to 180)
    death from cardiovascular cause 5 years 375
    (8.06%)    		 282
    (6.07%)    		 25%
    (13% to 35%)    		 1.99%
    (0.95% to 3.03%)    		 50
    (33 to 110)
    myocardial infarction 5 years 567
    (12.2%)    		 460
    (9.90%)    		 19%
    (9% to 28%)    		 2.29%
    (1.01% to 3.56%)    		 44
    (28 to 99)
    stroke 5 years 226
    (4.86%)    		 157
    (3.38%)    		 30%
    (15% to 43%)    		 1.48%
    (0.67% to 2.29%)    		 68
    (44 to 150)
    heart failure 5 years 545
    (11.7%)    		 426
    (9.17%)    		 22%
    (12% to 31%)    		 2.54%
    (1.30% to 3.79%)    		 39
    (26 to 77)
    cardiac arrest 5 years 58
    (1.25%)    		 37
    (0.80%)    		 36%
    (4% to 58%)    		 0.45%
    (0.042% to 0.86%)    		 222
    (116 to 2408)
    worsening angina 5 years 1221
    (26.2%)    		 1107
    (23.8%)    		 9%
    (3% to 15%)    		 2.41%
    (0.65% to 4.18%)    		 41
    (24 to 150)
    revascularisation 5 years 864
    (18.6%)    		 742
    (16.0%)    		 14%
    (6% to 21%)    		 2.60%
    (1.06% to 4.13%)    		 38
    (24 to 94)
    new diagnosis of diabetes 5 years 154
    (5.34%)    		 105
    (3.70%)    		 31%
    (12% to 46%)    		 1.64%
    (0.57% to 2.72%)    		 61
    (37 to 180)
    complications from diabetes 5 years 344
    (7.39%)    		 289
    (6.22%)    		 16%
    (2% to 28%)    		 1.17%
    (0.15% to 2.20%)    		 85
    (46 to 670)
    discontinued therapy permanently 5 years 1429
    (30.7%)    		 1516
    (32.6%)    		 -6%
    (-13% to -0.086%)    		 -1.92%
    (-3.81% to -0.028%)    		 -52
    (-3500 to -26)
    treatment discontinued due to cough 5 years 85
    (1.83%)    		 340
    (7.32%)    		 -301%
    (-406% to -217%)    		 -5.49%
    (-6.33% to -4.65%)    		 -18
    (-22 to -16)

    Comments

    1. 65% of patients were still taking ramipril after 5 years.
    2. At 5 years, systolic blood pressure in the ramipril group had fallen by only 2 mmHg, and diastolic by 3 mmHg.

    Citation

    1. The Heart Outcomes Prevention Evaluation Study Investigators , : Effects of an angiotension-converting-enzyme inhibitor, ramipril on death from cardiovascular causes, myocardial infarction, and stroke in high-risk patients. New England Journal of Medicine 2000; 334: -
    Search Terms: hand-search
    Contributor: Chris Ball and Musab Hayatli, November 1999
    Reviewer:

    Clinical Question.
    Patient high-risk for cardiovascular disease, stroke, diabetes, myocardial infarction, peripheral vascular disease
    Intervention or Exposure ramipril
    Comparison placebo
    Outcome death, myocardial infarction