Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding), by inconsistency (variability in results), and by imprecise results (few patients and outcome events for each comparison).
A Cochrane review [Abstract] 1 included 8 studies with a total of 3 610 subjects with peripheral arterial disease (PAD). Four studies compared anti-hypertensive therapy against placebo and 4 studies compared 2 anti-hypertensive treatments with each other. Studies were not pooled due to the variation of the comparisons and the outcomes presented.
2 studies compared ACE inhibitors against placebo. In the HOPE study there was a significant reduction in cardiovascular events in ramipril group (OR 0.72, 95% CI 0.58 to 0.91; 1 study, n=1725). In the second trial (n=54) using perindopril, there was a marginal increase in claudication distance (MD 8.0 m, 95% CI 0.49 to 15.51) but no change in ankle brachial index (ABI) (MD 0, 95% CI -0.03 to 0.03) and a reduction in maximal walking distance (MD -46.00 m, 95 % CI -69.74 to -22.26). The third trial (n=95) in patients undergoing angioplasty suggested that the calcium antagonist verapamil compared to placebo reduced restenosis, although this was not reflected in the maintenance of a high ABI. A study (n = 36) comparing telmisartan to placebo found a significant improvement in maximum walking distance at 12 months with telmisartan (median 191 m, interquartile range (IQR) 157 to 226 versus 103 m, IQR 76 to 164; P < 0.001) but no differences in ABI or arterial intima-media thickness (IMT).
A small study (n=56) demonstrated no significant difference in arterial intima-media thickness with men receiving the thiazide diuretic hydrochlorathiazide compared to those receiving the alpha-adrenoreceptor blocker doxazosin. Two studies compared the beta-adrenoreceptor blocker nebivolol with either the thiazide diuretic HCTZ or with metoprolol. Both studies found no significant differences in intermittent or absolute claudication distance, ABI, or all-cause mortality between the anti-hypertensives. A subgroup analysis of PAD patients (n = 2 699) in a study which compared a calcium antagonist-based strategy (verapamil slow release ± trandolapril) to a beta-adrenoreceptor blocker-based strategy (atenolol ± hydrochlorothiazide) found no significant differences in the composite endpoints of death, non-fatal myocardial infarction or non-fatal stroke (OR 0.90, 95% CI 0.76 to 1.07) or death, non-fatal MI or non-fatal stroke and revascularisation (OR 0.96, 95% CI 0.82 to 1.13).
Lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.
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