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Acute Pain | Chronic Pain | General

Effects of beta-blockers on intermittent claudication

Clinical bottom line

For short-term beta-blocker interventions (up to eight weeks), compared with placebo there appear to be no significant differences in walking capacity. However, this is based on trials with very small group sizes, and longer-term trials are needed to answer the question of whether it is advisable to prescribe beta-blockers for long-term use in patients with peripheral arterial disease. An updated review using only highre quality trials found a significant worsening in walking distance.

See updated review below


Beta-adrenergic blockers have been contraindicated in peripheral arterial disease because of the perceived risk that these drugs could worsen intermittent claudication. The concern is that interventions which might lower systemic arterial blood pressure could potentially adversely affect limbs with impaired blood flow. Standard anti-hypertensive therapy is therefore sometimes not recommended, and beta-blockers in particular, which diminish cardiac output and block skeletal muscle vasodilation, have been avoided.

Reference

Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med. 1991; 151: 1769-1776

Systematic review

Inclusion criteria were randomised controlled trials comparing beta-blockers with placebo or other inactive control; patients with symptomatic peripheral arterial disease of the lower extremities; English language reports; walking capacity outcomes.

Differences between the mean change in walking capacity during treatment and control periods were extracted from trials together with standard deviations. Standard errors were converted to standard deviations. These data were used to calculate an effect size with 95% confidence intervals. In most cases, the data were extracted for pain-free walking distances. Individual effect sizes were weighted by trial size and pooled for overall effect size. Effect sizes were regarded as significantly different to placebo when confidence intervals overlapped zero.

Findings

Trials were generally in middle-aged male patients with mild to moderate stable intermittent claudication which had usually persisted for at least six months. Trials varied in terms of treatment protocols, doses, duration (ten days to eight weeks), clinical end points and trial quality. Included drugs were non-selective beta-adrenergic antagonists (propranolol hydrochloride), or beta 1 -selective antagonists (metoprolol tartrate, atenolol, labetalol hydrochloride) or beta-blockers with intrinsic sympathomimetic activity (pindolol and acebutolol).

Of the eleven included trials, four had group sizes of less than ten, and the largest group was 23. Eight trials were double-blind, and a further two were blinded for outcomes.

In eleven of eleven trials there were no significant differences in effect size between beta-blockers and placebo for either pain-free or maximum walking distance.

Walking capacity:

Seven comparisons were included in the analysis of pain-free walking distance. Effect sizes were small, with five of seven comparisons having negative values suggesting reduced, but not significantly reduced, pain-free walking distance with beta-blockers when compared with placebo. The overall treatment effect size was -0.24 (-0.62 to 0.14), and was not significant.

Six comparisons were included in the analysis of maximum walking distance. Effect sizes were small, with four of six comparisons having negative values suggesting reduced, but not significantly reduced, maximum walking distance with beta-blockers when compared with placebo. The overall treatment effect size was -0.29 (-0.71 to 0.12), and was not significant.

Other measures:

These included pain-free and maximum exercise times and peak calf blood flow. Although methods of measuring these varied, there were no significant differences on any of the exercise outcomes. In one of three trials there was a significant improvement in peak calf blood flow, although the clinical relevance of this is unclear.

Adverse effects

Adverse effects were not covered in this review.

Updated Review

An updated review [1] covers much the same ground, but perhaps in more detail, and limited to randomised, blind trials, so that it actually had only nine trials included, despite being later. IT found a significant worsening in maximum walking distance.

  1. R Miyajima et al. Beta-adrenergic blocking agents and intermittent claudication: systematic review. Yakugaku Zasshi 2004 124: 825-831.