Outcome trials

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The ASCOT study further attests to the benefit ofthe combination of an ACE inhibitor with a dihydropyridine calcium antagonist [54]. ASCOT was designed to compare the effect of the standard antihypertensive regimen (a beta-blocker and a diuretic) with that of a more contemporary regimen (calcium antagonist and an ACE inhibitor) on coronary artery disease.

A total of almost 20,000 patients were randomized to either atenolol plus bendroflumethiazide (if needed) or amlodipine plus perindopril (if needed). The trial was interrupted prematurely because of distinct benefits in the amlodipine/perindopril arm. Specifically, compared with atenolol/ thiazide, amlodipine/perindopril resulted in a significant reduction in all-cause mortality and coronary events of about 15%, a reduction in fatal and nonfatal stroke of 25%, a reduction in cardiovascular mortality of 25%, and an impressive reduction in new-onset diabetes of 30% (Figure 23).

Although BP with amlodipine/perindopril was lowered by a further 2.9/1.8 mmHg than with atenolol/bendroflumethiazide, it seems unlikely that this small decrease in BP would account for the impressive benefits.

In the randomized, double-blind Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, 11,506 patients with hypertension who were at high risk for cardiovascular events were randomized to either benazepril plus amlodipine or benazepril plus HCTZ [57]. The study was terminated early because there was a significant 20% reduction in primary outcome events (cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization) in the benazepril/amlodipine arm when compared with the benazepril/HCTZ arm. The authors concluded that, in this population, the benazepril/amlodipine

Incidence of new-onset diabetes

Time (years)

Number at risk

Amlodipire-based regimen 9639 9383 9165 8966 8726 7618 (567 events)

Atenolol-based regimen 9618 9295 9014 8735 8455 7319 (799 events)

Time (years)

Number at risk

Amlodipire-based regimen 9639 9383 9165 8966 8726 7618 (567 events)

Atenolol-based regimen 9618 9295 9014 8735 8455 7319 (799 events)

Figure 23 Incidence of new-onset diabetes. HR, hazard ratio. Reproduced with permission from Dahlofetal. [54].

combination was superior to the benazepril/HCTZ combination in reducing cardiovascular events. BP was lowered to the same extent in both combination arms. Of note, many patients in the ACCOMPLISH trial had previous coronary artery disease and diabetes and perhaps, therefore, do not fully represent the broad population of patients with hypertension. Nevertheless, it seems that RAS blockade plus amlodipine confers more benefits than does RAS blockade plus HCTZ.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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