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Jul 14, 2008 By: Walter Alexander, Ph.D.
Prominent among this year's clinical trials presented at the American Society of Hypertension Annual Meeting were some looking at the potential benefits of antihypertensive therapies, especially combination therapies, in specific populations. In some trial selections reviewed below, benefits were absent or limited to specific groups.
AASK trial results
Across initial and long-term follow-up phases of the AASK (African American Study of Kidney Disease and Hypertension) trial, angiotensin converting enzyme (ACE) inhibitor therapy led to favorable trends but no significant benefit in the primary composite endpoint (doubling of serum creatinine from trial baseline, end-stage renal disease, or death). Among patients with significant proteinuria at baseline, however, endpoint reductions were highly significant for both the initial trial and five-year follow-up cohort phases, according to Jackson Wright, M.D., Case Western Reserve University, Cleveland, Ohio.
Previously published results of the first phase of AASK had shown that among the 1,094 Blacks with non-diabetic, hypertensive chronic kidney disease, the ACE inhibitor ramipril was more effective than the calcium antagonist amlodipine besylate or the beta-blocker metoprolol in slowing hypertensive renal disease progression. No differences were seen between patients randomized to the lower mean arterial (MAP) blood pressure goal of <92 mmHg (equivalent ~125/75 mmHg) or to the higher MAP of 102-107 mmHg (equivalent of ~140/90 mmHg) regardless of UP/Cr ratio at baseline. In reaching target BP levels, investigators had added further agents, if required, in the following recommended order: furosemide, doxazosin mesylate, clonidine hydrochloride, or hydralazine hydrochloride (or minoxidil, if needed).
In the subsequent cohort study phase of AASK, reported here by Wright, all participants received recommended therapy with ramipril or an angiotensin receptor blocker (AR targeting <130/80 mmHg as a blood pressure goal. For the composite primary outcome after 132-month follow-up, there was a highly significant benefit in the lower blood pressure group (hazard ratio [HR]=0.72) among those with baseline UP/Cr >0.22, and a weakly reversed trend (HR 1.18) across both phases favoring those in the usual blood pressure group.
Wright concluded, "Patients with hypertensive renal disease who have significant proteinuria greater than 300 mg/day do appear to benefit from a lower blood pressure goal of less than 130/80 mmHg."
While it has been known that ACE inhibitors reduce CV mortality and morbidity in patients with vascular disease or high-risk diabetes without heart failure, the role of an ARB prescribed separately or combined with an ACE inhibitor in this population has been unknown. Michael Weber, M.D., SUNY Downstate Medical Center College of Medicine, Brooklyn, N.Y., reviewing late-breaking clinical trials, said that the ONTARGET trial investigators enrolled 25,620 subjects (>55 years) with coronary heart disease or diabetes plus additional risk factors but without heart failure evidence. They were given either ramipril 10 mg/day, telmisartan 80 mg/day, or the combination and followed for a mean of 55 months.
Presenting data on the ramipril/telmisartan (R/T) combination versus ramipril (R) alone, Weber reported that BP reductions were increased with the combination as compared with R alone (systolic/diastolic-8.4/-6.0 mmHg R/T; -6.0/-4.6 mmHg R). Treatment discontinuations were 20% more frequent with the combination, however. Relative risk for time to the primary outcome (MI, stroke, CHF hospitalization, CV death) was virtually identical at 0.99 for R/T versus R, and there was increased risk of developing nephropathy in the R/T group (RR=1.21). Other adverse events, including syncope, renal dysfunction, and need for dialysis, were worse with the combination.
Weber concluded, "Combination therapy with an ARB + ACE inhibitor is not recommended for prevention of vascular events in this population. This does not necessarily rule out this type of therapy in selected patients with heart failure or CKD."
In the BENIFORCE study, 81% of patients with stage I hypertension receiving stepped titration of an ARB-based regimen achieved the JNC 7 blood pressure (BP) goal of <140/90 mmHg and 60% achieved the more stringent target of <130/80 mmHg, according to Steven G. Chrysant, M.D., University of Oklahoma School of Medicine, Tulsa. In the placebo arm of the study, the goals were reached by 43% and 7%, respectively.
Results of BENIFORCE trial
The BENIFORCE trial included 276 patients with stage 1 or 2 hypertension. They were randomized to the ARB olmesartan medoxomil (Benicar, Daiichi Sankyo) 20 mg/day or placebo, and then titrated upward at three-week intervals if they did not reach a target of <120/80 mmHg according to the following schedule: olmesartan 40 mg/day (weeks four to six), olmesartan plus hydrochlorothiazide (HCTZ) 40/12.5 mg/day (weeks seven to nine), and olmesartan/HCTZ 40/25 mg/day (weeks 10 to 12). Patients were maintained on medication doses as long as BP was controlled.
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作者:admin@医学,生命科学 2011-07-10 05:50
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