When blood pressure is consistently high it can lead to complications such as a heart attack (myocardial infarction) or stroke. Both peripheral arterial disease (PAD), a condition that affects the blood vessels (arteries) carrying the blood to the legs, arms, and stomach area, and high blood pressure (hypertension) are associated with atherosclerosis. This is hardening of the arteries which is caused by deposits of fat, cholesterol and other substances inside the blood vessels. PAD is diagnosed when the blood supply to the legs is restricted causing pain and cramping that limits walking (intermittent claudication). It is measured by the walking distance (on a treadmill) before onset of pain (claudication distance) or ankle brachial index (ABI), the ratio of the blood pressure in the arms to the blood pressure in the legs. If the blood pressure is lower in the legs compared to the arms (ABI of less than 1.0) this indicates blocked arteries in the legs (or PAD). PAD can progress to pain at rest and critical limb ischaemia (sudden lack of blood flow to a limb caused by a blood clot or fatty deposit blockage) that requires revascularisation (restoring the blood flow by opening up the blocked blood vessel) or amputation. Treatment of hypertension to reduce cardiovascular events (heart attack or stroke) and death needs careful consideration in people with PAD. Anti-hypertensive medications may worsen the PAD symptoms by further reducing blood flow and supply of oxygen to the limbs, and may have long-term effects on disease progression. The evidence from randomised controlled trials (RCTs) examining the risks and benefits of various anti-hypertensive drugs on measures of PAD is lacking.
We identified eight RCTs with a total of 3610 people with symptomatic PAD where participants were randomised to receive an anti-hypertensive treatment for at least one month or placebo or no treatment. Four studies compared an anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. The studies were not combined due to the variation of comparisons and the outcomes presented. One trial with 1725 participants showed that the angiotensin converting enzyme (ACE) inhibitor ramipril was effective in reducing the number of cardiovascular events by 28% compared to placebo. In one other study using an ACE inhibitor (n = 52) the perindopril group showed a small increase in claudication distance but no change in ABI and a reduction in maximal walking distance (MWD). In patients undergoing peripheral arterial angioplasty (a procedure to open narrowed or blocked blood vessels) the results from a trial with 96 participants suggested that the calcium channel blocker verapamil reduced restenosis (new blockage of the artery) at six months. In one small study (n = 80) peripheral arterial wall thickness was similar whether men received the thiazide diuretic hydrochlorothiazide (HCTZ) or the alpha-adrenoreceptor blocker doxazosin. In another small study (n = 36) MWD was improved at 12 months in the angiotensin-II receptor antagonist telmisartan group compared to the placebo group but there were no significant differences in ABI or arterial wall thickness. Another study (n = 163) found no significant differences in intermittent or absolute claudication distance, ABI, all-cause mortality or non-fatal cardiovascular events after 24 weeks of treatment in the beta-adrenoreceptor blocker nebivolol group and the HCTZ group. A study comparing two beta-adrenoreceptor blockers, nebivolol and metoprolol, found no clear differences in intermittent or absolute claudication distance, ABI, all-cause mortality or revascularisation after 36 weeks of treatment. A subgroup analysis of PAD patients (n = 2699) in the final study revealed no significant differences in the combined endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation between the calcium antagonist-based strategy (verapamil slow release (SR) with or without trandolapril) compared to the beta-adrenoreceptor blocker strategy (atenolol with or without HCTZ).
The evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is not known whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in hypertensive PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.