CAPPP trial

Abstract

As physicians in charge of many hypertensive patients, we are worried by the results of the CAPPP trial.1Hansson L Lindholm LH Niskanen L et al.Effect of angiotensin-convertingenzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.Lancet. 1999; 353: 611-616Summary Full Text Full Text PDF PubMed Scopus (1912) Google Scholar The frequency of stroke, a secondary outcome in CAPPP, was significantly higher in the captopril group than in controls. Stroke is known to be the outcome presenting the strongest association with blood and its treatment.Several significant differences between treatment groups in baseline characteristics, including blood pressure, the proportion of males, and the prevalence of diabetes, might partly account for the difference in outcome. Lennart Hansson and colleagues1Hansson L Lindholm LH Niskanen L et al.Effect of angiotensin-convertingenzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.Lancet. 1999; 353: 611-616Summary Full Text Full Text PDF PubMed Scopus (1912) Google Scholar did multivariate adjustments to take into account these differences. Adjusted and unadjusted results were similar, however, leaving the difference in stroke rate statistically significant.There is no way to be certain that such adjustments provide an unbiased estimate of treatment effect: the only way to prevent bias is careful randomisation. How should we apply the CAPPP results to clinical practice? Attributing to chance and therefore ignoring the between-group difference in stroke rate is a responsibility that we do not endorse. We look forward to having the results from the other largescale trials that compare various ACE inhibitors with diuretics, β-blockers, or calcium channel antagonists. Meanwhile, we suggest that frequency of stroke should be compared in the groups given ACE inhibitors or alternative treatments in databases from trials in patients with heart failure2Garg R Yusuf S Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE inhibitor Trials.JAMA. 1995; 273: 1450-1456Crossref PubMed Scopus (1756) Google Scholar or myocardial infarction.3ACE Inhibitor Myocardial Infarction Collaborative GroupIndications for ACE inhibitors in the early treatment of acute myocardial infarction. Systematic overview of individual data from 100 000 patients in randomized trials.Circulation. 1998; 97: 2202-2212Crossref PubMed Scopus (624) Google Scholar The stroke rate is admittedly lower in these clinical settings than in hypertensive patients, but the overall numbers of patients (including a consistent minority of hypertensive patients) in these trials was much larger than those in CAPPP. This approach would provide an unbiased estimate of the difference in stroke rate, if any, between ACE inhibition and conventional treatment or placebo. As physicians in charge of many hypertensive patients, we are worried by the results of the CAPPP trial.1Hansson L Lindholm LH Niskanen L et al.Effect of angiotensin-convertingenzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.Lancet. 1999; 353: 611-616Summary Full Text Full Text PDF PubMed Scopus (1912) Google Scholar The frequency of stroke, a secondary outcome in CAPPP, was significantly higher in the captopril group than in controls. Stroke is known to be the outcome presenting the strongest association with blood and its treatment. Several significant differences between treatment groups in baseline characteristics, including blood pressure, the proportion of males, and the prevalence of diabetes, might partly account for the difference in outcome. Lennart Hansson and colleagues1Hansson L Lindholm LH Niskanen L et al.Effect of angiotensin-convertingenzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.Lancet. 1999; 353: 611-616Summary Full Text Full Text PDF PubMed Scopus (1912) Google Scholar did multivariate adjustments to take into account these differences. Adjusted and unadjusted results were similar, however, leaving the difference in stroke rate statistically significant. There is no way to be certain that such adjustments provide an unbiased estimate of treatment effect: the only way to prevent bias is careful randomisation. How should we apply the CAPPP results to clinical practice? Attributing to chance and therefore ignoring the between-group difference in stroke rate is a responsibility that we do not endorse. We look forward to having the results from the other largescale trials that compare various ACE inhibitors with diuretics, β-blockers, or calcium channel antagonists. Meanwhile, we suggest that frequency of stroke should be compared in the groups given ACE inhibitors or alternative treatments in databases from trials in patients with heart failure2Garg R Yusuf S Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE inhibitor Trials.JAMA. 1995; 273: 1450-1456Crossref PubMed Scopus (1756) Google Scholar or myocardial infarction.3ACE Inhibitor Myocardial Infarction Collaborative GroupIndications for ACE inhibitors in the early treatment of acute myocardial infarction. Systematic overview of individual data from 100 000 patients in randomized trials.Circulation. 1998; 97: 2202-2212Crossref PubMed Scopus (624) Google Scholar The stroke rate is admittedly lower in these clinical settings than in hypertensive patients, but the overall numbers of patients (including a consistent minority of hypertensive patients) in these trials was much larger than those in CAPPP. This approach would provide an unbiased estimate of the difference in stroke rate, if any, between ACE inhibition and conventional treatment or placebo. CAPPP trialAuthors' reply Full-Text PDF