In the United States there are over 70 million people with a blood pressure that is “categorically” labeled as being in the hypertensive range (systolic blood pressure ≥140 mm Hg). If treatment were based on a patient’s absolute risk of having a cardiovascular (CV) event and not just a categorical blood pressure, many more Americans would need drug therapy. Perhaps this is why high blood pressure (HBP) mortality increased 26% from 1994 to 2004 despite a large armamentarium of available drug therapies.1 Another possibility could be that blood pressure (BP) reduction is not a valid surrogate outcome for cardiovascular morbidity and mortality. That is, just lowering BP is not enough to decrease CV events; how you lower the BP may be more important.
Jamerson and colleagues recently published the results of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial.2 This landmark study enrolled over 11,000 patients with hypertension and increased CV risk (defined as having a history of prior coronary events, myocardial infarction, revascularization, or stroke, impaired renal function, peripheral arterial disease, left ventricular hypertrophy, or diabetes mellitus). Patients were randomly assigned in a one-to-one ratio to either of two treatment groups. These two groups consisted of a once daily regimen of benazepril 20 mg plus amlodipine 5 mg or benazepril 20 mg plus hydrochlorothiazide (HCTZ) 12.5 mg. After one month, the benazepril component could be increased to 40 mg daily. If a patient still did not reach target BP (<140/90 or <130/80 for patients with diabetes mellitus or kidney disease), amlodipine could be increased to 10 mg daily or HCTZ could be increased to 25 mg daily. The addition of other antihypertensive agents was permitted excluding any calcium-channel blocker and angiotensin converting enzyme inhibitor (ACEI), or any angiotensin II-receptor blocker (ARB). The primary endpoint was measured as the time to the first event (defined as a composite of CV event and death from CV causes).
Nearly 14,000 patients were screened and 5,744 were assigned to the benazepril-amlodipine group and 5,762 to the benazepril-HCTZ group. The average age of the entire cohort was 68 years. Males comprised 60% of the groups. Only 12% were black. Seventy-four percent of the patients were on 2 or more antihypertensive medications prior to the study; 64% were on antiplatelet agents and 68% were on lipid-lowering medications. There were no significant differences in baseline characteristics between the patients in the two treatment groups. The mean duration of treatment exposure was 30 months. In each group, 32% of the patients received approved antihypertensive agents in addition to the highest dose of study medications.
The baseline blood pressures were similar between the two groups and the degree of BP reduction from baseline was also similar. In the benazepril-amlodipine group (5463 patients), the mean BP after dose titration was 131.6/73.3 mm Hg versus 132.5/74.4 mm Hg in the benazepril-HCTZ group (5474 patients). The mean difference in BP between the two groups was 0.9 mm Hg systolic and 1.1 mm Hg diastolic (P<0.001). Blood pressure control was achieved in 75.4% of the benazepril-amlodipine arm and in 72.4% of the benazepril-HCTZ arm. The primary-outcome event occurred in 9.6% in the benazepril-amlodipine group as compared with 11.8% in the benazepril-HCTZ group, representing an absolute risk reduction of 2.2% (hazard ratio, 0.80; P<0.001). A number needed to treat (NNT) to prevent one CV event or death from a CV event would be 45. Cumulative discontinuation rates between the regimens were similar.
The authors concluded that the regimen of benazepril-amlodipine was superior to the benazepril-HCTZ combination in preventing CV complications in patients with HTN and increased CV risk. Dr. Chobanian, in an accompanying editorial, commented on these unexpected results.3 He points out that most comparison trials evaluating the treatment of HTN have failed to show significant differences in primary outcomes as long as ...