Effect of blood pressure lowering medications on leg ischemia in peripheral artery disease patients: A meta-analysis of randomised controlled trials

Abstract

Background: It has been suggested that anti-hypertensive medications may worsen leg ischemia in peripheral artery disease (PAD) patients. We undertook a meta-analysis to assess the effect of anti-hypertensive medications on measures of leg ischemia including maximum walking distance (MWD), pain free walking distance (PFWD) and ankle brachial pressure index (ABPI). A meta-regression was performed to evaluate whether the effect of the anti-hypertensive medications on mean arterial pressure (MAP) was associated with changes in ABPI, MWD or PFWD. Method: A systematic literature search was performed to identify placebo controlled randomized control trials (RCT) testing anti-hypertensive medications, which reported baseline and followup measurements of: MAP and MWD, PFWD or ABPI in patients with intermittent claudication (IC) due to PAD. Result: A meta-analysis was performed on 5 RCTs comprising a total of 180 and 127 patients receiving anti-hypertensive medications and placebo respectively. This analysis suggested that anti-hypertensive medication did not significantly affect MWD, PFWD or ABPI. In contrast, the meta-regression analysis showed that the reduction in MAP due to the anti-hypertensive drugs was positively correlated with increased MWD during follow-up (β = 8.371, p = 0.035). Heterogeneity across studies, as assessed by I2, was high. The follow-up period within the included trials was generally short with 3 out of 5 studies having a follow-up period of ≤ 6 weeks. Conclusion: This study suggests that anti-hypertensive treatment does not worsen but may improve leg ischemia in PAD patients. Larger multicenter trials with longer anti-hypertensive treatment periods are required to clarify the effect of anti-hypertensives on leg ischemia in PAD patients.