CAPPP trial

Abstract

The CAPPP trial investigators1Hansson L Lindholm LH Niskanen L et al.Effect of angiotensin-converting-enzyme 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 (1914) Google Scholar are to be congratulated on completing the first comparison of β-blockers and diuretics with one of the newer classes of antihypertensives. Are they also to be consoled for their failure to find the hoped for benefits of ACE inhibition?—only if hypertension is regarded as a homogeneous syndrome, and only if the prior hypothesis were one-tailed. In cancer, treatments that are effective for one type are unlikely to be effective if all types of cancer were included in a trial. The hypothesis that one class of antihypertensive agent is more effective than another is based on the premise that height of blood pressure is not the sole determinant of outcome. Although the division of hypertension into high-renin (vasoconstrictive) and low-renin (saltdependent) types is too simplistic, there is evidence that those with highrenin type disease are more at risk of ischaemic heart disease, and low-renin of stroke.2Alderman MH Madhavan S Ooi WL Cohen H Sealey JE Laragh JH Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension.N Engl J Med. 1991; 324: 1098-1104Crossref PubMed Scopus (696) Google Scholar In a comparison of ACE inhibitors and diuretics, with opposite effects on the renin system, it would be unsurprising if there were different trends, as in CAPPP, for the cardiovascular and cerebrovascular outcomes in the two groups. This issue might be clearer if Lennart Hansson and co-workers were to clarify what proportion of the control group was receiving diuretics, and whether indeed there were any differences in outcome (in either group) for which diuretic use was a significant variable. Hansson et al attribute the 25% higher stroke rate in the captopril group to the small (<2 mm Hg) differences in prestudy and treated diastolic pressures. This attribution seems contrary to the two-tailed spirit of the trial. In the HOT study,3Hansson L Zanchetti A Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principle results of the Hypertension Optimal Treatment (HOT) randomised trial.Lancet. 1998; 351: 1755-1762Summary Full Text Full Text PDF PubMed Scopus (5417) Google Scholar the flatness of the stroke outcome curve for blood pressures values less than 90 mm Hg incline one to look elsewhere for an explanation. Kaplan-Meier curves for stroke might help us to judge whether the significant excess in the ACE inhibitor group is greatest when the blood pressure difference is maximum, early in the course of the trial. The MRC Mild Hypertension Trial,4MRC Working PartyMRC trial of treatment of mild hypertension: principal results.BMJ. 1985; 291: 97-104Crossref PubMed Scopus (1791) Google Scholar in which diuretics were twice as effective as β-blockade in preventing stroke, is probably the strongest argument for expecting differences in efficacy between classes. After this trial, we proposed that the benefit of high dose diuretics could have been due to a protective effect of angiotensin II against strokes, and wondered whether an ACE inhibitor might contrarily, show a failure of protection.5Brown MJ Brown J Does angiotensin-II protect against strokes?.Lancet. 1986; ii: 427-429Summary Scopus (49) Google Scholar CAPPP does not resolve the issue, since captopril given once or twice daily would not eliminate angiotensin- II receptor stimulation. Fortunately, as the investigators point out, results of other trials comparing old and new drugs will soon be upon us. It would be disappointing if these trials did not yield some surprises from which we can eventually learn a bit more than we already know about hypertension. CAPPP trialAuthors' reply Full-Text PDF