ASH: More Proves Better in Treating Hypertension

CHICAGO, May 23 -- Fixed combination doses of a calcium-channel blocker and an angiotensin-receptor blocker appear to improve hypertension treatment, researchers said here. In two similar trials presented at the American Society of Hypertension, the investigators showed that when it comes to treating high blood pressure, more is often better than less.
The combination of the calcium channel blocker amlodipine and an angiotensin-receptor blocker -- either valsartan or olmesartan -- resulted in a greater reduction of high blood pressure without a major cost in serious adverse events, they found.
In one trial patients who were unsuccessful in controlling blood pressure on a single anti-hypertensive drug, were switched to the combination of amlodipine at 5 mg or 10 mg and valsartan at 160 mg (Exforge).
"Exforge represents a very favorable combination of valsartan and amlodipine," said Joseph Izzo Jr., M.D., of the State University of New York at Buffalo. "This can be applied widely instead of or after monotherapy for patients not previously controlled."
The second trial involved 12 different groups of patients who were assigned either placebo or amlodipine at 5 mg or 10 mg of monotherapy or olmesartan at 10 mg, 20 mg, or 40 mg monotherapy or six doses of combination therapy with olmesartan and amlodipine (Azor).
"All combinations of amlodipine and olmesartan produced significantly greater mean reductions in both diastolic and systolic blood pressure than either medication alone," said Steven Chrysant, M.D., of the University of Oklahoma in Oklahoma City.
Dr. Izzo enrolled 894 patients in his study, all of whom were being treated with some form of monotherapy -- diuretics, calcium channel blockers, beta blockers, ACE inhibitors, or angiotensin receptor blockers -- but were still above the treatment goal of 140 mm Hg systolic blood pressure and 90 mm Hg diastolic pressure.
The researchers in the study, funded by Novartis, assigned 443 patients to receive the 5 mg amlodipine/160 mg valsartan combination and 451 patients to receive the 10 mg amlodipine/160 mg valsartan dose of the combination.
Overall, 81.3% of the patients on the 5/160 mg formulation of Exforge achieved the blood pressure goal at week 16 compared with 87.6% of patients on the 10/160 mg dose, Dr. Izzo said. "The outcomes were very favorable in all populations tested and at both the 5/160 and the 10/160 doses. All were very well tolerated and the blood pressure control was consistent across all groups."
Dr. Chrysant and colleagues enrolled 1,940 patients in the phase III, eight-week, randomized, double-blind, placebo-controlled, parallel group study, that averaged around 160 patients per group. All the patients in the study had mild-to-severe hypertension, defined as a seated diastolic from 99 mg Hg to 120 mm Hg.
In the study,
The patients on placebo reduced seated diastolic pressure by 3.5 mm Hg;
The patients on olmesartan 40 mg monotherapy reduced diastolic pressure by 10.9 mm Hg;
The patients on amlodipine 10 mm Hg monotherapy reduced diastolic pressure 13.3 mm Hg;
The patients on amlodipine by 10 mg/olmesartan 160 mg -- the highest dose of the combination -- reduced diastolic blood pressure 19.4 mm Hg.
All active agents, monotherapy or combination were statistically significantly superior to placebo at the P<0.0001 level.
He noted that the adverse event rate for the highest combination dose was similar to that of placebo. Serious adverse events were few, and the one death in the study occurred to a patient who was a murder victim, he said, and was not related to the drug.