Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension

 

Abstract

Background

ACE inhibitors 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 ACE inhibitors 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 ACE inhibitor compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension.

Data collection and analysis

Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was collected from the trials.

Main results

Ninety two trials evaluated the dose-related trough BP lowering efficacy of 14 different ACE inhibitors in 12 954 participants with a baseline BP of 157/101 mm Hg. The data do not suggest that any one ACE inhibitor is better or worse at lowering BP. A dose of 1/8 or 1/4 of the manufacturer's 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 90% of Max. ACE inhibitor doses above Max did not significantly lower BP more than Max. Combining the effects of 1/2 Max and higher doses gives an estimate of the average trough BP lowering efficacy for ACE inhibitors as a class of drugs of -8 mm Hg for SBP and -5 mm Hg for DBP. ACE inhibitors reduced BP measured 1 to 12 hours after the dose by about 11/6 mm Hg.

Authors' conclusions

There are no clinically meaningful BP lowering differences between different ACE inhibitors. The BP lowering effect of ACE inhibitors is modest; the magnitude of trough BP lowering at one-half the manufacturers' maximum recommended dose and above is -8/-5 mm Hg. 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 ACE inhibitors because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials. 

 

Plain language summary

ACE inhibitors for the treatment of high blood pressure

The class of drugs called ACE inhibitors is commonly used for the treatment of elevated blood pressure. This class includes drugs such as ramipril (brand name: Altace), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril) and quinapril (Accupril). 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 the trials that had assessed this question.

We found 92 trials that randomly assigned participants to take either an ACE inhibitor or an inert substance (placebo). These trials evaluated the blood pressure lowering ability of 14 different ACE inhibitors in 12 954 participants. The trials followed participants for approximately 6 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 ACE inhibitor drug appears to be any better or worse than others in terms of blood pressure lowering ability.

Most of the trials in this review were funded by companies that make ACE inhibitors and serious adverse effects were not reported by the authors of many 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 ACE inhibitor in lower doses will lead to substantial cost savings, and possibly a reduction in dose-related adverse events. 

 

摘要

背景

血管收縮素轉換?抑制劑 (angiotensin converting enzyme, ACE)對原發性高血壓的降壓療效

血管收縮素轉換?抑制劑已廣泛使用於治療高血壓，因此決定並比較其對於血壓與心跳之效果，以及因副作用停用藥物(withdrawals due to adverse effects, WDAE) 等是很重要的。

目標

針對治療原發性高血壓，決定血管收縮素轉換?抑制劑的劑量性關係和安慰劑，對於降低收縮壓和 (或) 舒張壓的療效。

搜尋策略

我們搜尋CENTRAL (The Cochrane Library 2007年, 第一期), MEDLINE (1966年至2007年2月), EMBASE (1988年至2007年2月) 和參考文獻表單上的參考文章。

選擇標準

以隨機雙盲安慰劑對照試驗評估以單一固定劑量的血管收縮素轉換?抑制劑和安慰劑，治療原發性高血壓3至12週後，其血壓下降之療效。

資料收集與分析

兩位作者獨立的評估偏差之危險性和擷取資料。與試驗之作者接觸，以獲得額外的資料，也從試驗中收集因副作用停用藥物的資料。

主要結論

92 個試驗，12,954位基礎血壓為157/101毫米汞柱的受試者身上，評估14種不同的血管收縮素轉換?抑制劑之劑量性相關的降血壓療效。這些數據顯示沒有任何一種血管收縮素轉換?抑制劑的降壓效果較強。使用製造商建議每日最高劑量(Max)的1/8或1/4劑量，即可達到每日最高劑量降壓效果的百分之60 – 70；使用製造商建議每日最高劑量的1/2劑量，可達到每日最高劑量降壓效果的百分之90；若劑量超過製造商建議每日最高劑量，則不會顯著增加降壓療效。綜合製造商建議每日最高劑量的1/2劑量或更高劑量可以估算出，血管收縮素轉換?抑制劑這類藥物可降收縮壓8毫米汞柱和舒張壓5毫米汞柱。血管收縮素轉換?抑制劑在服藥後1 – 12小時，可降低血壓約11/6毫米汞柱。

作者結論

不同血管收縮素轉換?抑制劑並沒未在臨床上有意義的不同降壓療效。血管收縮素轉換?抑制劑的降壓效果是適度的用製造商建議每日最高劑量的1/2或更高劑量可降血壓約 8/5毫米汞柱。此外，用建議的起始劑量就可以達到百分之60 – 70的降壓效果。因為許多試驗時間很短且未報告副作用，所以這篇回顧性文章無法提供血管收縮素轉換?抑制劑造成傷害的比率。

翻譯人

本摘要由臺北榮民總醫院羅元豪翻譯。

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

總結

血管收縮素轉換?抑制劑對於高血壓的治療：這類藥物叫做血管收縮素轉換?抑制劑，常被用來治療高血壓。這類藥物包含ramipril, captopril, enalapril, fosinopril, lisinopril and quinapril。我們想問的是：這類藥物降血壓的效果有多好？個別藥物之間是否有差異？我們試著搜尋目前可獲得的科學文獻來回答這個問題。我們找到92個隨機分配受試者服用血管收縮素轉換?抑制劑或安慰劑的試驗。這些試驗評估14個不同的血管收縮素轉換?抑制劑在 12,954位受試者，降血壓的療效 (追蹤約6週)，不同血管收縮素轉換?抑制劑在降壓方面似乎沒有多大差異，而且此類藥物在起始劑量時就可以達到大部分的降壓效果；最佳預估降壓效果約8/5毫米汞柱。因為試驗時間很短且未報告副作用，所以這篇回顧性文章無法提供預測這類藥物造成的傷害。