American Society of Hypertension, Inc., 23rd Annual Scientific Meeting and Exposition

Hypertensive patients (n = 1,940) across a broad range of often problematic subgroups were treated effectively with Azor (Daiichi Sankyo), a combination of Pfizer’s calcium antagonist amlodipine (Norvasc) and Daiichi Sankyo’s angio-tensin-receptor blocker (ARB) olmesartan medoxomil (Benicar). In a large registration trial using prespecified analyses, Dr. Bakris found that these randomly assigned, double-blind subgroups all benefited from the combination, compared with patients receiving monotherapy. The subgroups consisted of 481 African-American patients; 241 Hispanic/Latino subjects; 1,256 participants with a body mass index (BMI) of 30 kg/m2 or more; and 258 diabetic patients. Twelve regimens were as follows: 8 weeks of amlodipine 5 mg/day or 10 mg/day as monotherapy; olmesar tan 10 mg/day, 20 mg/day, or 40 mg/day as monotherapy; and each of the six possible combinations of these doses of amlodipine and olmesartan; or placebo. Dr. Bakris reported that the antihypertensive efficacy of amlodipine/olmesartan was similar among patients with or without diabetes. Patients starting the combination were more likely to achieve the recommended blood pressure (BP) goal of 130/80 mm Hg. Among patients with diabetes, only 10% to 13% achieved that goal, compared with 55% to 60% of non-diabetic participants. He also said that among obese patients, regardless of BMI, benefits were generally clinically meaningful and greater with the combination therapy, although they were somewhat lower among subjects with higher BMIs. With the highest dose of the combination, systolic BP among patients with higher BMIs was reduced by 20.6 mm Hg and diastolic BP was reduced by 17.9 mm Hg. In patients with BMIs lower than 30 kg/m2, systolic BP was reduced by 30.6 mm Hg and diastolic BP was reduced by 20.6 mm Hg. The percentages of patients receiving combination therapy who achieved BP goals at the eighth week also tended to be greater if the BMI was below 30 kg/m2 (41%–55%) than if the BMI was higher (28%–52%). “Olmesartan should reduce the edema associated with amlodipine,” Dr. Bakris stated. Higher edema rates associated with amlodipine monotherapy (40.3% at 10 mg/day) were attenuated in the combination treatment groups (25.2%–28.8%). Dr. Oparil said that mean reductions in systolic and diastolic BP were significantly greater with amlodipine/olmesartan than with olmesartan alone in African-American patients, except in the case of systolic BP in those treated with amlodipine 5 mg/day and olmesartan 10 mg/day. She emphasized that with amlodipine/olmesartan 10/40 mg/day, the magnitude of BP reductions in the African-American patients (−29 mm Hg/−16 mm Hg) approached that of the non–African-American patients (−31 mm Hg and −20 mm Hg, respectively). For Hispanic/Latino patients, all combinations resulted in greater systolic and diastolic BP reductions than with mono-therapy. In addition, reductions were similar among His-panic/Latino patients and non–Hispanic/Latino subgroups. In the BENIFORCE trial (Benicar Efficacy: New Investigative Findings show Olmesartan medoxomil safely and effectively Reduces blood pressure Compared with placEbo), 276 patients with stage 1 or 2 hypertension were randomly assigned to receive olmesartan 20 mg/day or placebo. This dose was then titrated upward at three-week intervals if patients did not reach a target of below 120/80 mm Hg according to the following schedule: olmesartan 40 mg/day (weeks 4 to 6), olmesartan plus hydrochlorothiazide (HCTZ) 40/12.5 mg/day (weeks 7 to 9), and olmesartan/HCTZ 40/25 mg/day (weeks 10 to 12). Patients were maintained on their current medication doses as long as BP was controlled to target levels, stated Dr. Chrysant. The trial’s primary endpoint was the mean difference in BP reduction between the olmesartan-based regimen and placebo. Systolic BP was reduced by 22.1 mm Hg; diastolic BP was decreased by 12.2 mm Hg. In patients with stage I hypertension (140–159 mm Hg systolic BP and 90–99 mm Hg diastolic BP), Dr. Chrysant said that 81% of those receiving stepped titration of the receptor ARB-based regimen achieved BP below 140/90 mm Hg—the Joint National Commission’s (JNC 7) BP goal—and 60% achieved the stricter target of below 130/80 mm Hg. In the placebo arm, only 43% and 7%, respectively, achieved these goals. Dr. Kereiakes reported on 148 patients with stage 2 hypertension (systolic: 160 mm Hg and above; diastolic, 100 mm Hg and above). Mean differences from placebo were − 22.5 mm Hg systolic BP and −13.2 mm Hg diastolic BP. Overall, for patients receiving olmesartan-based therapy, treatment-related adverse events were not significantly increased. Commenting on all of these findings, Dr. Bakris said that olmesartan alone “is a very good starting choice for patients with stage I hypertension without diabetes.” He recommended initial monotherapy with a diuretic or calcium antagonist for stage I elderly or African-American patients. For those with stage 2 hypertension, he said, “I start with combination therapy on top of lifestyle modification.”