Drug Topics - February 11, 2008 - (Page HSE15) FEBRUARY 11, 2008 HSE 15 Clinical Practice sure (SBP) than either olmesartan or amlodipine alone. Compared head to head, olmesartan plus thiazide (40 mg, plus 12.5 or 25 mg) outperformed amlodipine plus benazepril (5 mg to 10 mg, plus 20 mg). The former combination gave a mean 33 mmHg SBP reduction from baseline, versus 27 mmHg for the latter. Among those in the olmesartan/thiazide group, 66% reached a goal of 140/90 mmHg or lower, and 33% achieved 130/80 mmHg or below. In the amlodipine/benazepril group, 45% reached the first goal, with 14% reaching the second goal. Like Jamerson, Punzi strongly advocated initial combination treatment. In an interview with Drug Topics, Punzi said he understood the reluctance of many clinicians to start off with a strong combination therapy. “The drugs in the old days dropped pressure so rapidly that it was dangerous, and a lot of family physicians became very concerned. But now we have much better drugs. The fixed-dose combinations are very carefully put together.” Steven Chrysant, M.D., Oklahoma Cardiovascular and Hypertension Center, showed that carefully combining a calcium-channel blocker (CCB) and an ARB can greatly improve blood pressure control without increasing side-effect risk. He studied the combination of olmesartan, 10mg to 40 mg daily, plus amlodipine, 5 mg to 10 mg daily, versus either drug alone or placebo, in 1,940 patients with mild to severe hypertension. “Each combination had significantly greater reductions in diastolic and systolic blood pressures compared with both of its monotherapy components,” said Chrysant. “The greatest observed mean reductions occurred with amlodipine 10 mg and olmesartan 40 mg. High-dose monotherapy with both amlodipine and olmesartan give good pressure reductions, but only the combination can get you below 140 mmHg.” He noted that in addition to reducing systolic pressure, the combination produces a strong diastolic blood pressure-lowering effect. Adverse events Chrysant added that there was no meaningful difference in adverse-event rates between the combination therapy and the monotherapies. In fact, by adding progressively increasing doses of olmesartan, the amlodipine dose can be diminished, reducing foot edema. “This is a big deal, especially for female patients. If a woman cannot get her shoes on because of foot swelling, she’ll stop taking the medications!” Jamerson concluded that it is time to put the old “start low, go slow” strategy to rest. “There are millions of patients out there taking meds and not being well controlled,” he said. “Initial combination therapy is very effective, and there’s now substantial evidence to support broadening the use of combination therapy as an initial treatment.” THE AUTHOR is a clinical writer based in New York.
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