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. 

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. 

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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 strategy: 

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.

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