Drug Topics - February 11, 2008 - (Page HSE12) 12 HSE DRUG TOPICS FEBRUARY 11, 2008 www.drugtopics.com Clinical Practice New data support combo therapy at outset of hypertension treatment Walter Alexander, Ph.D. mong the various offerings at the American Society of Hypertension’s 2007 annual meeting in Chicago, several new studies strongly supported the use of fixed-dose antihypertensive combination therapy at the outset of hypertension treatment. For years, hypertension experts have argued that monotherapy seldom gets blood pressures down to goal and that combination therapy is a better treatment option. Current guidelines, however, including the 7th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), call “There’s now substantial for a stepped approach, beginning first with one drug, then adding evidence to support others. Until recently, advocates broadening the use of initial combination therapy did of combination therapy not have data to make their case. Studies presented at the annual as an initial treatment.” meeting could help change that. Kenneth Jamerson, M.D., The Avoiding Cardiovascular University of Michigan Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, a multicenter study of high-risk hypertensive patients from the United States, Sweden, and Norway, is the first true outcomes study testing combination therapy as a comprehensive strategy. A total of 12,600 hypertensive individuals with heart disease, renal disease, or target organ damage were randomized to either amlodipine and benazepril (5 mg and 20 mg) or benazepril and hydrochlorothiazide (20 mg and 12.5 mg). After one month, benazepril was increased to 40 mg in both groups. After the second month, amlodipine or thiazide doses were doubled. After the third month, investigators could add on any other drugs. Nearly all patients had been receiving some antihypertensive drug therapy prior to enrollment, said lead investigator Kenneth Jamerson, M.D., of the Univer- A sity of Michigan. While 74% were receiving two or more single agents, only 38% were controlled to less than 140/90 mmHg. The value of this trial, according to Jamerson, is that by switching patients from their existing regimens to one of two fixed-dose combinations, a valuable comparison can be made between monotherapies and fixed-dose combinations. Impressive results The results, Jamerson added, were impressive. Systolic pressure dropped from a baseline mean of 145.4 mmHg to 131.8 mmHg after 18 months. Most patients were in the 132 mmHg range by six months. U.S. patients went from a baseline of 142.4 mmHg to 129.4 mmHg. “We got them below 130 mmHg. I am very proud of this,” Jamerson said. “That’s never been seen in U.S. trials.” Though ACCOMPLISH was not a diabetes trial, 60% of patients had Type 2 diabetes. Jamerson noted that even in this hard-to-treat cohort, the combo therapies dropped mean systolic blood pressure (SBP) from 145.2 mmHg to 131.5 mmHg. The proportion of patients deemed well controlled (below 140/90 mmHg) went from 37.6% to 75.6%. “We more than doubled the number who are well controlled,” said Jamerson. This was accomplished, in most cases, with the fixed-dose combos alone. Only 15% of patients needed an add-on drug; only 6% needed two. Adverse-event rates were few and mild, with dizziness, cough, and edema being the most common. Roughly 2% of patients became hypotensive. “We assumed both combinations would reduce pressures down to target. Perhaps one is better than the other, but we are not really testing that,” said Jamerson. He added, however, that combining a calcium-channel blocker (CCB) with an ACE inhibitor may increase nitric oxide production, thus improving vascular function. Initial treatment Henry Punzi, M.D., director of the Punzi Medical Center and Hypertension Research Institute, Carrollton, Texas, suggested that combinations containing an angiotensin II receptor blocker (ARB) may be ideal for initial treatment. That view was based on his 12-week study comparing olmesartan medoxomil (Benicar, Daiichi Sankyo) plus thiazide with amlodipine plus benazepril in 190 patients with stage 2 hypertension. Both combinations were more effective in lowering systolic blood pres- Photo: Jim Shive http://www.drugtopics.com
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