Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension

 

Abstract

Background

Angiotensin receptor blockers (ARBs) are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE).

Objectives

To quantify the dose-related systolic and/or diastolic BP lowering efficacy of ARBs versus placebo in the treatment of primary hypertension.

Search methods

We searched CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to February 2007), EMBASE (1988 to February 2007) and reference lists of articles.

Selection criteria

Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. WDAE information was collected from the trials.

Main results

Forty six RCTs evaluated the dose-related trough BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 156/101 mm Hg. The data do not suggest that any one ARB is better or worse at lowering BP. A dose of 1/8 or 1/4 of the manufacturers’ maximum recommended daily dose (Max) achieved a BP lowering effect that was 60 to 70% of the BP lowering effect of Max. A dose of 1/2 Max achieved a BP lowering effect that was 80% of Max. ARB doses above Max did not significantly lower BP more than Max. Due to evidence of publication bias, the largest trials provide the best estimate of the trough BP lowering efficacy for ARBs as a class of drugs: -8 mm Hg for SBP and -5 mm Hg for DBP. ARBs reduced BP measured 1 to 12 hours after the dose by about 12/7 mm Hg.

Authors' conclusions

The evidence from this review suggests that there are no clinically meaningful BP lowering differences between available ARBs. The BP lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg.  Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

 

Plain language summary

Angiotensin receptor blockers for the treatment of high blood pressure

A class of drugs called angiotensin receptor blockers (ARBs) is commonly used to lower high blood pressure. This class includes drugs such as losartan (brand name: Cozaar), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis) and valsartan (Diovan). We asked how much this class of drugs lowers blood pressure and whether there is a difference between individual drugs within the class. The available scientific literature was searched to find all trials that had assessed these questions.

We found 46 trials that randomly assigned participants to take either an ARB or an inert substance (placebo). These trials evaluated the BP lowering ability of 9 different ARBs in 13 451 participants altogether. The trials followed participants for only 7 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest.  There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure.  Most of the blood pressure lowering effect (about 70%) can be achieved with the lowest recommended dose of the drugs.  No ARB appears to be any better or worse than others in terms of blood pressure lowering ability.

Almost all of the trials in this review were funded by companies that make ARBs and serious adverse effects were not reported by the authors of half of these trials.  This could mean that the drug companies are withholding unfavorable findings related to their drugs.  Due to incomplete reporting of  the number of participants who dropped out of the trials due to adverse drug reactions, as well as the short duration of these trials, this review could not provide a good estimate of the harms associated with this class of drugs.  Prescribing the least expensive ARBs in lower doses will lead to substantial cost savings, and possibly a reduction in dose-related adverse events. 

 

摘要

背景

血管張力素受體阻滯劑對於原發性高血壓之降壓效果

血管張力素受體阻滯劑(ARBs)被廣泛用於治療高血壓，因此決定及比較它們對血壓(BP)、心率與因不良反應停藥(WDAE)的效應是必要的。

目標

在使用血管張力素受體阻滯劑的劑量與安慰劑，比較用於治療原發性高血壓時，量化相關劑量對於收縮壓及/或舒張壓降壓效果。

搜尋策略

我們搜尋CENTRAL (The Cochrane Library 2007, Issue 1)、MEDLINE (1966 to February 2007)、EMBASE (1988 to February 2007)及文章所列的參考資料。

選擇標準

雙盲、隨機、控制的試驗，病人為原發性高血壓，評估固定劑量血管張力素受體阻滯劑單一療法與安慰劑相比之降低血壓療效，為期3至12週。

資料收集與分析

二位作者獨立評估試驗的品質及擷取資料。我們與研究作者聯繫並取得額外的資訊。收集在試驗中因不良反應而停藥的資訊。

主要結論

46個隨機控制試驗評估了9種血管張力素受體阻滯劑，在13451位受試者，基礎血壓為156/101毫米汞柱，其劑量相關的谷底(trough)血壓降低效果。資料並不建議任何一種血管張力素受體阻滯劑有較佳或較差的降血壓效果。1/8或1/4的製造商建議每日最大劑量(Max)可達成其降血壓效果的60至70%。1/2的製造商建議每日最大劑量可達成其降血壓效果的80%。劑量超過製造商建議每日最大劑量無法顯著增加其降血壓效果。因為出版偏差的證據，最大型的試驗提供血管張力素受體阻滯劑作為一種藥品其谷底血壓降低效果的最佳估計值：收縮壓−8毫米汞柱及舒張壓−5毫米汞柱。血管張力素受體阻滯劑可降低於用藥後1至12小時量測的血壓約12/7毫米汞柱。

作者結論

這篇綜合論述的證據建議，在所有可取得的血管張力素受體阻滯劑之間，並無臨床有意義的降血壓效果差異。血管張力素受體阻滯劑的降血壓效果適度，作為藥品種類與血管張力素轉換?抑制劑的效果類似；最大建議劑量或以上之血管張力素受體阻滯劑降低平均谷底血壓幅度是−8/−5毫米汞柱。此外，建議起始劑量可達成其60至70%的谷底血壓降低效果。這篇文獻回顧因為試驗的期間短及許多試驗缺乏不良反應的報告所致，無法提供與血管張力素受體阻滯劑對傷害有關發生率的良好估計值。

翻譯人

本摘要由臺北榮民總醫院楊元豪翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

血管張力素受體阻滯劑對於升高的血壓之治療：一種稱為血管張力素受體阻滯劑(ARBs)的藥物，被經常用於輔助降低升高的血壓(BP)。這種類的藥物包括losartan、candesartan、eprosartan、irbesartan、telmisartan及valsartan。我們詢問這種類的藥物可降低多少血壓以及這類藥物個別之間是否有差異。我們搜尋可取得的科學文獻，找到所有試驗的證據來評估這個問題。篩選46個隨機分配受試者服用血管張力素受體阻滯劑或是無藥性物質(安慰劑)的試驗。這些試驗評估了9種血管張力素受體阻滯劑在13451位受試者於約7週的血壓降低效果。沒有任一種血管張力素受體阻滯劑顯示出較佳或較差的血壓降低效果，且大部分的血壓降低效果發生在最初起始劑量。平均降低谷底血壓效果的最佳估計值是適度的，−8/−5毫米汞柱，與血管張力素轉換?抑制劑這類藥物的效果相同。因為報告的缺乏及試驗的短期，這篇文獻回顧無法提供與這類藥物有關傷害的良好估計值。