Benazepril plus amlodipine results in fewer cardiovascular events than benazepril plus hydrochlorothiazide

The authors evaluated the effectiveness of two different drug combinations in reducing cardiovascular events in patients with hypertension and coronary artery disease.

Patients with hypertension (high blood pressure) combined with certain risk factors such as older age, diabetes, kidney disease, increased mass of the wall of the left ventricle (a chamber in the heart), coronary heart disease and established disease of the blood vessels are at increased risk of cardiovascular events. A previous study established that a combination of benazepril (Lotensin; an angiotensin-converting enzyme inhibitor that causes relaxation of the blood vessels) and amlodipine (Norvasc; a calcium-channel blocker that relaxes the muscles of the arteries) was more effective at reducing cardiovascular events than a combination of benazepril and hydrochlorothiazide (Microzide; a diuretic that inhibits the kidneys' ability to retain water) in high-risk elderly patients with stage 2 hypertension.

The aim of this study was to evaluate whether this remained true in patients with hypertension and coronary artery disease.

The trial evaluated 11,506 participants who had hypertension with or without coronary artery disease. The majority of patients were older than 65 years of age. Of these, 5,744 were randomly assigned to receive benazepril plus amlodipine while 5,762 were randomly assigned to receive benazepril and hydrochlorothiazide. 5,314 (46%) were classified as having coronary artery disease at the beginning of the study. The average follow-up was 35.7 months for those taking benazepril plus amlodipine and 35.6 months for those taking benazepril plus hydrochlorothiazide.

In coronary artery disease patients, average systolic blood pressure (pressure when the heart is contracting) dropped from 144 mmHg to 130 mmHg in the benazepril plus amlodipine group, and from 144 mmHg to 131 mmHg in the benazepril plus hydrochlorothiazide group.

In the coronary artery disease group, 13% of the benazepril plus amlodipine group experienced either cardiovascular morbidity or mortality. Cardiovascular morbidity included nonfatal heart attack, nonfatal stroke, hospitalization for unstable severe pain in the chest or coronary revascularization (re-establishment of blood flow) procedures. Cardiovascular mortality included death from heart attack, stroke, coronary intervention or heart failure. 16% of the benazepril plus hydrochlorothiazide group experienced either cardiovascular morbidity or mortality.

Therefore, benazepril plus amlodipine was associated with an 18% reduction in the chances of experiencing cardiovascular morbidity or mortality compared to benazepril plus hydrochlorothiazide. There were 20% fewer events in the benazepril plus amlodipine group.

In those patients with coronary artery disease, 5.74% of the benazepril plus amlodipine group experienced cardiovascular-related mortality (death), heart attack or stroke compared to 8% of the benazepril plus hydrochlorothiazide group. This resulted in a 25% reduction in the chances of experiencing cardiovascular-related mortality, heart attack or stroke for the benazepril plus amlodipine group compared to the benazepril plus hydrochlorothiazide group.

In those with coronary artery disease, the rate of mortality from any cause was 4% in the benazepril plus amlodipine group compared to 5.14% in the benazepril plus hydrochlorothiazide group, indicating a 23% reduction in the chance of mortality from any cause for the benazepril plus amlodipine group.

The authors concluded that benazepril plus amlodipine may be a more favorable therapy in elderly patients with hypertension and coronary artery disease.