Review: β-blockers do not reduce walking capacity or calf blood flow in peripheral arterial disease
ACP J Club. 1992 Jan-Feb;116:3. doi:10.7326/ACPJC-1992-116-1-003
Radack K, Deck C. β-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 Sep;151:1769-76.
To review the relevant literature to determine if β-blocker therapy reduces treadmill exercise capacity or otherwise exacerbates intermittent claudication in patients with peripheral arterial disease.
Index Medicus, MEDLINE, textbooks, reviews, and article bibliographies were searched for the period 1966 through 1990.
22 clinical studies of peripheral arterial disease were identified. 11 were included for analysis because they were randomized, controlled trials comparing β-blockers with a placebo or nonplacebo control. These studies evaluated changes in pain-free walking capacity, maximal walking distance, and calf blood flow with β-blocker therapy.
Study quality was assessed with a standard scoring system. Patient characteristics, study interventions, outcomes, and complications were extracted. Treatment effect sizes were calculated for each study as the difference between outcomes in the treatment and control groups.
With 1 exception, studies were crossover in design; treatment durations ranged from 10 days to 8 weeks. Study quality scores ranged from 5 to 14.5 of a possible 18 points; ascertainment of end points was blinded in 10 studies. Patients (n = 127) were generally middle-aged or elderly men with mild-to-moderate, stable intermittent claudication of ≥ 6 months duration. Patients with hypertension were included in 9 studies, with 1 study not giving this information. Drugs compared were primarily propranolol (nonselective) and metoprolol or atenolol (β1-selective).
No significant differences in treatment effect size (TES) between groups assigned to β-blockers or control were found for any intrastudy comparison. Results could be pooled for between 4 and 7 studies for comparison of the effects of β-blockers on the different end points. β-blockers did not reduce pain-free walking distance (TES -0.24 m, 95% CI -0.62 to 0.14 m) or maximum walking distance (TES -0.29 m, CI -0.71 to 0.12 m) on an exercise treadmill or maximum exercise duration (TES 0.05 min, CI -0.39 to 0.49 min). Calf blood flow was not reduced with either β1-selective or nonselective drugs.
The pooled results of 11 small trials show that β-blockers do not adversely affect walking capacity or worsen intermittent claudication symptoms in patients with mild-to-moderate peripheral arterial disease.
Source of funding: Not stated.
Article reprints: Not available.
Peripheral arterial disease is a common disorder. Patients with peripheral arterial disease often have coexistent coronary artery disease and hypertension for which β-adrenergic blockers are effective treatments. However, case reports that emerged soon after the release of propranolol indicated that β-adrenergic blocker therapy exacerbated the symptoms of intermittent claudication. These adverse effects may have been related to reduced peripheral blood flow caused by either a lowering of the systemic blood pressure or by vasoconstriction from blocking peripheral β2-adrenergic receptors. Therefore, it became clinical practice not to administer β-adrenergic blockers to patients with claudication. This bias may have significantly reduced the use of a clinically important class of drugs in patients with peripheral arterial disease who also had angina, arrhythmias, or hypertension.
After the release of propranolol, several β1-selective adrenergic blockers were developed that offered the potential advantage of not adversely affecting the peripheral circulation. In patients with claudication, several small randomized trials compared different classes of β-adrenergic blockers with placebo to evaluate the effects on claudication severity, treadmill exercise performance, and calf blood flow. Radack and Deck reviewed these trials and subjected those with the highest quality to a meta-analysis. Their results confirm that no class of β-adrenergic blocker adversely affected claudication severity or calf blood flow. The physiologic significance of these findings is that calf blood flow in normal and diseased persons is not primarily regulated by sympathetic tone. Clinically, patients with peripheral arterial disease may receive the benefits of β-adrenergic blockers in the treatment of other disorders without concern for worsening of their claudication. However, the early case reports should not be ignored because there may be occasional patients who should not use β-adrenergic blockers.
William R. Hiatt, MD
University of Colorado School of MedicineDenver, Colorado, USA