Drug combinations and all cause mortality in heart disease

Editor—Hippisley-Cox and Coupland conclude that the addition of angiotensin converting enzyme (ACE) inhibitors to combinations of drugs conferred no additional benefit in their study of patients in primary care with ischaemic heart disease.¹ However, such a conclusion should be reached with caution.

The drugs were given to the patients with the highest risk of death. A higher percentage of patients who died were treated with ACE inhibitors, and the greatest improvement in risk of death after adjustment for risk factors was seen in the patients treated with these drugs.

ACE inhibitors might thus have been given to the patients with the most severe disease in each comorbidity group—for example, to diabetic patients with kidney disease and to patients with the most severe heart failure. Therefore the study can give no indication of the crucial question whether the outcome would have been equally good for the group of 463 patients who probably had the most severe disease and received statins, aspirin, β blockers, and ACE inhibitors if they had not been given ACE inhibitors.

Replacement of yes or no for comorbidity factors with more discriminating variables, such as presence of microalbuminuria and a severity measure for heart disease, would probably have improved the study. However, this cannot replace the quality of a randomised, placebo controlled study comparing the effect of adding ACE inhibitors to the other study drugs. Therefore the study by Hippisley-Cox and Coupland adds no new knowledge to how patients with ischaemic heart disease in primary care should be treated.