Peripheral Artery Disease-Related Leg Ischemia and Antihypertensive Use

A meta-analysis published in PLoS One found that antihypertensive medication did not worsen leg ischemia and may improve maximal walking distance (MWD) in patients with peripheral artery disease (PAD).¹

As of 2010, approximately 200 million people globally had PAD, and an estimated 20% of these patients were expected to die from a cardiovascular-related event within 5 years.^2,3 These statistics underscore the need to aggressively manage cardiovascular risk factors in this population.

Hypertension has been observed in roughly half of patients with PAD, and 20% to 30% of patients receiving antihypertensive medication showed a reduction in cardiovascular events in previous research.^4,5

Various guidelines recommend the use of antihypertensives for patients with PAD with blood pressure greater than 140/90 mm Hg, although some of these agents, especially beta blockers, have not been indicated for patients with PAD because of peripheral perfusion concerns. However, others argue that blood pressure-lowering medications do not worsen leg ischemia. Previous findings have been mixed: Some studies reported improvement in leg ischemia measures in patients with PAD, and others did not.^6-8

In the present systematic review and meta-analysis, researchers at the Queensland Research Centre for Peripheral Arterial Diseases at James Cook University in Australia investigated associations between antihypertensive drugs and leg ischemia in patients with PAD and intermittent claudication. The analysis included 5 randomized controlled trials consisting of 180 patients who received antihypertensives and 127 patients who received placebo.

The results demonstrated that the medication had no effect on MWD, pain-free walking distance, or ankle brachial pressure index. However, the decrease in mean arterial pressure resulting from the medication was found to be positively correlated with MWD (β=8.371; P =.035), but not the other measures, during the follow-up period.

These findings indicate that antihypertensive treatment does not worsen leg ischemia and could improve MWD in patients with PAD with intermittent claudication.

“The role played by antihypertensives in improving outcomes is controversial and lacks sufficient evidence and has been clouded by retraction of 2 trials that reported positive outcomes,” the researchers noted.

References

1. Thomas Manapurathe D, Krishna SM, Dewdney B, Moxon JV, Biros E, Golledge J. Effect of blood pressure lowering medications on leg ischemia in peripheral artery disease patients: A meta-analysis of randomised controlled trials. PLoS One. 2017;12(6):e0178713. doi:10.1371/journal.pone.0178713
2. Fowkes FGR, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382(9901):1329-1340. doi:10.1016/S0140-6736(13)61249-0
3. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 Pt 2):S1-S296.
4. Novo S, Avellone G, Di Garbo V, et al. Prevalence of risk factors in patients with peripheral arterial disease. A clinical and epidemiological evaluation. Int Angiol. 1992;11(3):218-229.
5. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med. 1992;327(10):669-677. doi:10.1056/NEJM199209033271001
6. Bagger JP, Helligsoe P, Randsbaek F, Kimose HH, Jensen BS. Effect of verapamil in intermittent claudication A randomized, double-blind, placebo-controlled, cross-over study after individual dose response assessment. Circulation. 1997;95(2):411-414. doi:10.1161/01.CIR.95.2.411
7. Shahin Y, Cockcroft JR, Chetter IC. Randomized clinical trial of angiotensin-converting enzyme inhibitor, ramipril, in patients with intermittent claudication. Br J Surg. 2013;100(9):1154-1163. doi:10.1002/bjs.9198
8. Zankl AR, Ivandic B, Andrassy M, et al. Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease. Clin Res Cardiol. 2010;99(12):787-794. doi:10.1007/s00392-010-0184-0