Coronary heart disease: gemfibrozil decreased myocardial infarction and death due to heart disease.

Clinical bottom line (level 1b)

  1. Men with coronary heart disease and low levels of HDL cholesterol who were given gemfibrozil were less likely to have a nonfatal myocardial infarction or death due to coronary heart disease, than those given placebo (NNT = 23 at 5.1 years) .
  2. Men who were given gemfibrozil had no clear difference in stroke, than those given placebo.
Rubins et al: New England Journal of Medicine 1999; 341 (6): 410-418
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 20 Veterans; Affairs medical centres, USA

2531 patients (aged mean 64 years, 100% male) documented history of coronary heart disease (history of myocardial infarction, angina corroborated by objective evidence of ischaemia, coronary revascularisation or angiographic evidence of stenosis >50% of luminal diameter in one or more major epicardial coronary arteries)

Excluded if
  • aged >73 years
  • serious coexisting conditions
  • HDL cholesterol >40 mg per decilitre (1.0 mmol per litre)
  • LDL cholesterol >140 mg per decilitre (3.6 mmol per litre)
  • triglyceride level of >300 mg per decilitre (3.4 mmol per litre)


    • Note:
  • Block randomisation with stratification according to centre.


    • Control Group: (n = 1267, 1267 analysed): placebo
    Experimental Group: (n = 1264, 1264 analysed): slow-release gemfibrozil , 1200 mg once daily
    Later on in the study, the manufacturer of slow-release gemfibrozil discontinued production, regular gemfibrozil 600 mg twice daily was given.
    99.9% followed for 5.1 years Median follow-up was 5.1 years (range 0 to 6.9).
    Outcome notes:
    • nonfatal myocardial infarction or death due to coronary heart disease : sudden death, death due to MI, death due to congestive heart failure and death as a complication of invasive cardiac procedures.

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    nonfatal myocardial infarction or death due to coronary heart disease 5.1 years 275
    (21.7%)    		 219
    (17.3%)    		 20.0%
    (6.00% to 32.0%)    		 4.38%
    (1.30% to 7.46%)    		 23
    (12 to 77)
    stroke 5.1 years 76
    (6.00%)    		 58
    (4.59%)    		 24.0%
    (-7.00% to 45.0%)    		 1.41%
    (-0.33% to 3.15%)    		 71
    (NNT = 32 to infinity;
    NNH = 300 to infinity)

  • Analysis on raw events over a mean of 5.1y, without Kaplan-Meier analysis.

    • Comments

    1. A comparison with statins is required.
    2. Compliance was 75% in both groups.
    3. At the last follow-up session, 71% of each group were still taking their assigned medication.

    Citation

    1. Rubins HB, Robins SJ, Collins D, et al: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. New England Journal of Medicine 1999; 341 (6): 410-418
    Contributor: Clare Wotton and Bob Phillips, January 2000
    Reviewer: Edward Havranek

    Clinical Question.
    Patient coronary heart disease
    Intervention or Exposure gemfibrozil
    Comparison placebo
    Outcome major cardiovascular events