To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: All Angiotensin II Receptor Antagonists Have Similar Antihypertensive Efficacy URL: http://www.pslgroup.com/dg/1D0E5A.htm Doctor's Guide May 9, 2000
MONTREAL, QC -- May 9, 2000 -- A new meta-analysis published in the latest journal of American Journal of Hypertension shows that all four members of the newest class of antihypertensive drugs - angiotensin II antagonists or AIIAs - lower blood pressure with similar efficacy when administered at their usual recommended doses. Previous studies have already established that the AIIAs are as effective at lowering blood pressure as the older classes of antihypertensives such as beta blockers, calcium channel blockers and angiotensin-converting-enzyme (ACE) inhibitors. "Based on our analysis of published data from 11,000 patients, we conclude that there are no differences in efficacy within the AIIA class of blood pressure lowering medications," said Dr. David Spence, Study investigator, Internal medicine, Stroke Prevention and Atherosclerosis Research Centre, London, Ontario. Losartan (Cozaar®), the first of the AIIAs to be approved, was the most widely used drug in the new study. This international study, of which Dr. Spence is a co-author, was conducted with experts in treating high blood pressure from the U.S., Brazil, Japan and England. this is the first study to examine such a large series of data on the efficacy of this new and rapidly growing class of medicines. Several smaller studies have been previously published that suggest differences in both duration and magnitude in the blood pressure lowering effect of these drugs, whereas the larger studies show more similarities than differences. This meta-analysis concludes that there are no clinically relevant differences in the effectiveness of these agents. "A few direct comparisons within the AIIA drug class have been reported, some showing differences in efficacy between the agents and others no difference. These former results are not consistent with the current findings in our pooled analysis. This difference in findings could be due to methodological issues, including sample sizes that may limit the interpretation of the findings from these direct comparison studies. In the largest published study that compared losartan and valsartan (involving 1369 participants), no statistically significant differences were shown in the reduction of DBP from baseline, which is consistent with our pooled analysis," said Dr. Spence. The researchers also found that adding a low dose (12.5 mg) of the diuretic hydrochlorothiazide (HCTZ) intensified the initial dose of the AIIA significantly. This suggests that physicians may consider adding HCTZ to the AIIA to enhance the effect and enable them to reach their blood pressure goal. "This has for sometime been the logical choice for patients who fail on monotherapy," said Dr. Spence. More data on the efficacy of the combination of an AIIA and HCTZ will be available soon from large ongoing clinical trials including the LIFE study (The Losartan Hypertension Survival Study) which uses losartan plus HCTZ in a single presentation (HYZAAR ®). To determine the efficacy of the four AIIAs (losartan, valsartan, irbesartan and candesartan), the investigators calculated the absolute (i.e. non-placebo corrected) weighted average blood pressure reductions. They grouped the pooled analysis into three categories: AIIA monotherapy at starting dose; AIIA monotherapy with dose titration from starting to maximum dose; and starting dose AIIA combined with HCTZ. The results were as follows: Diastolic blood pressure (DBP) reduction: · AIIA monotherapy at starting dose - Range of responses: 8.2 to 8.9 mmHg (maximum difference between individual AIIA 0.7 mmHg) · AIIA monotherapy with dose titration - Range of responses: 9.5 to 10.5 mmHg (maximum difference between individual AIIA 0.9 mmHg) · AIIA starting dose plus HCTZ - Range of responses: 9.9 to 13.6 mmHg (maximum difference between individual AIIA 3.7 mmHg) Systolic blood pressure (SBP) reduction: · AIIA monotherapy at starting dose - Range of responses: 10.4 to 11.8 mmHg (maximum difference between individual AIIA 1.4 mmHg) · AIIA monotherapy with dose titration - Range of responses: 12.4 to 14.7 mmHg (maximum difference between individual AIIA 2.3 mmHg) · AIIA starting dose plus HCTZ - Range of responses: 16.1 to 20.6 mmHg (maximum difference between individual AIIA 4.5 mmHg) These small differences in blood pressure were not statistically significant. The addition of HCTZ to an AIIA also produced improvement in responder rates, which the authors defined as DBP < 90 mmHg and/or a DBP decrease of greater than or equal to 10 mmHg. The responder rate was approximately 50 percent for AIIA monotherapy at starting dose, rising to 55 percent after AIIA monotherapy titration. The AIIA/HCTZ combinations, however, demonstrated responder rates of approximately 70 percent. The study examined the antihypertensive efficacy of the four available AIIAs: losartan, valsartan, irbesartan and candesartan. The authors pooled all of the existing data from 43 randomized clinical trials of these four agents and conducted a meta-analysis that comprised 11,281 patients. This included randomized, double-blind placebo controlled trials of the four AIIAs versus placebo, comparing the AIIAs with other classes of antihypertensive therapy (diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium channel blockers) and combinations of AIIAs with diuretics. The analysis also included the limited number of "head-to-head" studies of AIIAs compared to each other. Patients included in the meta-analysis had mild to moderate hypertension (DBP 95-115 mmHg), as measured using sphygmomanometer and cuff (rather than ambulatory blood pressure monitoring) and no significant concomitant diseases. All studies used the doses recommended in the US, European and Japanese produce labels for the AIIAS. Treatment duration was typically four to six weeks with the starting dose prior to dose titration, followed by at least another four to six weeks until final assessment. Trials were excluded from the meta-analysis if they examined the use of AIIAs following lack of response to a drug from another class or if they used a dose of the AIIA not recommended in the product labeling. when analyzing the pooled data, the authors corrected for the size of different studies by assigning a greater weight to the results in proportion to the size of the study. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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