EFFECTS OF ANTIHYPERTENSIVE DRUGS ON CORONARY-ARTERY DISEASE RISK - AMETAANALYSIS

1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical s ignificance of these effects and the extent to which they persist duri ng long-term therapy is uncertain. 2. We performed a mete-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta(2)-adrenoce ptor intrinsic sympathominetic activity), enalapril, nifedipine and do xazosin on plasma cholesterol, low density lipoprotein cholesterol (LD L-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive effi cacy between the drugs, atenolol significantly (P<0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 year s for celiprolol). 6. The improvement in Framingham equation point sco res (systolic BP formula) was significantly (P<0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29- -0.78) than for celiprolol ( -1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11--2.23), enalapril (- 1.43; CI 0.23--3.07) and nifedipine (-1.91; CI -1.22--2.59). Similar r esults were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol on plasma lipids do not improve with prolonged therapy and are theoretically great eno ugh to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect pla sma lipids. However it must be emphasized that these are theoretical e ffects. In order to determine the actual differences between these dru gs on CAD end points, studies using these end points are required.