Combination Therapy With ARB and Amlodipine Effectively Reduces Blood Pressure

May 24, 2007 Chicago, IL - Two new studies presented this week at the American Society of Hypertension 2007 Scientific Sessions suggest that fixed-dose combination therapy with the calcium-channel blocker amlodipine and an angiotensin receptor blocker (ARB), either valsartan or olmesartan, can achieve significant reductions of blood pressure without an increase in serious adverse events [1,2].

During a press briefing announcing the results, Dr Joseph Izzo (State University of New York, Buffalo, NY), who presented data on amlodipine and valsartan, said the combination resulted in an additional 20-mm-Hg reduction in systolic blood pressure. These findings, in a cohort of patients who previously failed monotherapy, would translate into significant clinical benefit and should change thinking about how early and aggressively high blood pressure should be treated, he added.

"A number of us have been lobbying for years for combination therapy as step one," said Izzo. "Now, no fixed-dose combination drug is approved in the US for stage 1 hypertension, but in the guidelines we say that combination therapy is appropriate for any patient with stage-2 hypertension or beyond. We're still working this through. I would like to think that the attitudes are changing at the FDA, and that they realize a 20-mm-Hg increase in blood pressure doubles your cardiovascular risk. To me, that's a pretty hefty increase in risk, and one that begets the need for more aggressive therapy."

A study of real-world patients

In the study with valsartan and amlodipine, Izzo and colleagues enrolled 894 patients, all of whom were being treated with some form of monotherapy, including diuretics, calcium-channel blockers, beta blockers, ACE inhibitors, or ARBs. Despite treatment, blood pressures remained high, mean 150/90 mm Hg, above the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) treatment goal of 140 mm Hg systolic and 90 mm Hg diastolic blood pressure.

In total, 443 patients were randomized to receive the 5-mg-amlodipine/160-mg-valsartan combination and 451 patients to receive the 10-mg-amlodipine/160-mg-valsartan combination. After eight weeks, hydrochlorothiazide could be added, first at the 12.5-mg dose and then the 25-mg dose if needed.

At week 16, patients experienced an approximate 20-mm-Hg drop in systolic pressure over and above what they had achieved on previous monotherapy. More than 80% of patients treated with the 5/160-mg amlodipine/valsartan combination achieved the blood-pressure target compared with 87.6% of patients treated with the 10/160-mg dose. Diabetics also responded well, noted Izzo, with approximately 40% of diabetic patients getting to the treatment target of 130/80 mm Hg. The combination was also effective in African Americans, with good tolerability and few adverse events in all patients, said Izzo.

Commenting on the number of patients treated to target with the combination, Izzo said the control rates are approximately twice as good as those observed in the real world. Asked where he envisions the combination therapy fitting into clinical practice, Izzo said the efficacy of the drug in terms of blood-pressure lowering is similar to other drugs, including Lotrel (Novartis), an existing combination of amlodipine and the ACE inhibitor benazepril.

"It's another alternative and it's very well tolerated," he commented to the media. "The only difficulty with the older ACE inhibitor and calcium-channel blocker combination would occur in people who might get a cough, or something like that. . . . Perhaps there are minor reasons why a physician might pick one over another, but when it comes to blood pressure, I think we get very similar reductions."

Amlodipine and another ARB tested

Not to be outdone, investigators also presented data from a study evaluating the safety and efficacy of combination therapy with amlodipine and olmesartan in patients with mild to severe hypertension. Treatment with the combination resulted in significant reductions in seated systolic and diastolic blood pressure, they report.

In this second trial, led by Dr Steven Chrysant (University of Oklahoma School of Medicine, Oklahoma City), 12 groups of patients were assigned placebo, amlodipine 5-mg or 10-mg monotherapy; olmesartan 10-mg, 20-mg, or 40-mg monotherapy; or six doses of combination therapy with olmesartan and amlodipine. All 1940 patients in the study had mild to severe hypertension, defined as a seated diastolic blood pressure ranging from 99 mm Hg to 120 mm Hg.

Patients treated with olmesartan reduced their seated diastolic blood pressure 10.9 mm Hg, while those treated with amlodipine monotherapy reduced their seated diastolic pressure 13.3 mm Hg. Those treated with the maximum doses of amlodipine and olmesartan, 10/40 mg, had their seated diastolic pressure reduced 19.4%. All reductions were significant when compared with placebo.

The adverse-events profile of combination therapy was similar to monotherapy, said Chrysant.

1. Izzo J, for the study investigators. A randomized, double-blind, multicenter study to evaluate the efficacy of the combination of amlodipine and valsartan in hypertensive patients uncontrolled on previous monotherapy. American Society of Hypertension 2007 Scientific Sessions; May 21, 2007; Chicago, IL
2. Chrysant SG, Melino M, Karki S, et al. A randomized, double-blind, placebo-controlled factorial study evaluating the efficacy and safety of coadministration of amlodipine besylate plus olmesartan medoxomil compared to monotherapy in patients with mild to severe hypertension. American Society of Hypertension 2007 Scientific Sessions; May 21, 2007; Chicago, IL.

Source: http://www.medscape.com/viewarticle/557231?src=mp