Our goal in the management of hypertension is to help patients live longer without reducing their quality of life. Period. Several recent studies have finally begun to directly compare commonly used antihypertensives, and this Australian study adds to the database. The authors identified 6,083 healthy older patients (aged 65–84 years) in 1,594 family practices and followed them up for a median of 4.1 years. Patients were assigned to either an angiotensin-converting enzyme (ACE) inhibitor group or a diuretic group. The recommended drugs were enalapril and hydrochlorothiazide, but physicians could substitute other drugs in each class at their discretion. They could also prescribe b-blockers, calcium channel blockers, angiotensin-receptor blockers and a-blockers to achieve the blood pressure targets of 160/90mmHg, or 140/80mmHg if tolerated. This was an open-label trial, and allocation was appropriately concealed. Although often confused with blinding, allocation concealment refers to how patients get into a group, whereas blinding refers to what happens once they are in a group. You can and should have concealed allocation in an open-label trial. Analysis was by intention to treat, and groups were similar at baseline. Loss to follow-up was minimal. Like life, this study was messy in terms of who got what. Of those in the ACE inhibitor group, 58% were still receiving an ACE inhibitor at the end of the study period, and 65% were on monotherapy. In the diuretic group, 62% were still receiving a diuretic and 67% were on monotherapy. Few patients required three or more drugs: 6% in the ACE inhibitor group and 5% in the diuretic group. The most common second drug was a calcium channel blocker (22.9% in the ACE inhibitor group, 24.9% in the diuretic group), followed by b-blockers (10.8% and 13.7%) and angiotensin-receptor blockers (14.0% and 12.4%). The risk of death from any cause was similar between groups (15.7 vs 17.1 deaths per 1,000 patient-years; p=0.27). When they added cardiovascular events to deaths, there were slightly fewer in the ACE inhibitor group (56.1 vs 59.8 per 1,000 patient-years; p=0.05; number-needed-to- treat=270 to prevent one event over one year). Interestingly, there was no difference in the likelihood of cardiovascular events or all-cause mortality for women, but men had fewer cardiovascular events (but not all-cause deaths) when taking an ACE inhibitor.
Enalapril is better than hydrochlorothiazide at preventing cardiovascular events in older men. These results contrast with results from the recent ALLHAT, which found somewhat different outcomes between patients taking lisinopril and chlorthalidone in a group of patients 55 years and older with at least one cardiovascular risk factor. How to reconcile these findings? One possibility is that enalapril is more effective than lisinopril; another is that chlorthalidone is more effective than hydrochlorothiazide. Still another is that the design limitations of the current study (open-label design, in particular) may have overestimated the effect of the “more modern” drug. What we do know is that either is better than calcium channel blockers and a-blockers, both are cheaper than angiotensin-receptor blockers (with no evidence that angiotensin-receptor blockers are any better), and that ACE inhibitors may be better in older, lower-risk men.
Level of evidence
1b (see www.infopoems.com/resources/levels.html).
Individual randomised controlled trials (with narrow confidence interval).
Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003;348:583-92.