Studies in recent years have shown clinical benefits of angiotensin-converting enzyme (ACE) inhibitors beyond their ability to simply lower blood pressure ACE inhibitors appear to be of particular benefit in patients with congestive heart failure, and in a number of other cardiovascular disease states. The Second Australian National Blood Pressure Study Group pitted the ACE inhibitor enalapril against the diuretic hydrochlorothiazide in elderly patients to see which would provide the best protection against cardiovascular disease.

The trial was conducted by office-based family physicians in Australia under the direction of the Study Group. Trained study nurses checked patients for hypertensive blood pressure values and identified 31,255 eligible persons of age 65 to 84 years. Informed consent to participate in the trial was declined by 54 percent, and another 26 percent were excluded due to elevated creatinine level, contraindication to use of a study medication, a cardiovascular event within six months before study enrollment, or other clinical criteria. The remaining 6,083 persons were taken off any previously used antihypertensive medication and randomized to receive enalapril or hydrochlorothiazide. The blood pressure reduction goal was 140/80 mm Hg, if tolerated. Family physicians could add beta blockers, calcium channel blockers, or alpha blockers if needed to reach the blood pressure goal.

The median length of follow-up was 4.1 years. About two thirds of patients in each group were still on monotherapy at the end of the trial, while the remainder required additional medications to control blood pressure. Patients were followed for any cardiovascular event, including myocardial infarction, congestive heart failure, transient ischemic attack, stroke, death from any cardiovascular cause, and any need for angioplasty or other coronary artery procedure.

The enalapril group had 56.1 cardiovascular events per 1,000 patient-years, while the hydrochlorothiazide group had 59.8 events per 1,000 patient-years. The level of blood pressure reduction was nearly identical in the two groups. Women had only half as many events as men, and there were no statistically significant outcome differences between enalapril and hydrochlorothiazide among women.

The authors conclude that blood pressure reduction by the ACE inhibitor enalapril was associated with fewer cardiovascular events than use of the diuretic hydrochlorothiazide.

editor's note: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial compared diuretics with other antihypertensive drug classes and came to the opposite conclusion of this study, finding superior protection from cardiovascular disease with use of diuretics. The important similarities in both of these trials are (1) no overall survival difference among the different hypertension medications and (2) only small differences in specific cardiovascular events. Rather than quibbling over a few events per 1,000 patient-years for one drug class versus another, the likely point is to simply use whatever tolerable combination of medications is necessary to achieve adequate blood pressure reduction, thereby maximizing the prevention of cardiovascular morbidity and mortality.—b.z.