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Treatment of hypertension in peripheral arterial disease

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Abstract

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Background

Peripheral arterial disease (PAD) causes considerable morbidity and mortality. Hypertension is a risk factor for PAD. Treatment for hypertension must be compatible with the symptoms of PAD. Controversy regarding the effects of beta‐blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta‐blockers. Little is known about the effects of other classes of anti‐hypertensive drugs in the presence of PAD. This is an update of a Cochrane review first published in 2003.

Objectives

To determine the effects of anti‐hypertensive drugs on cardiovascular events and death, symptoms of claudication, critical leg ischaemia, progression of PAD and revascularisation or amputation in people with hypertension and PAD

Search methods

The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched May 2009) and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2). The authors studied abstracts of cardiology meetings.

Selection criteria

Randomised controlled trials of at least one anti‐hypertensive treatment against placebo, or two anti‐hypertensive medications against each other, with interventions lasting at least one month. Trials had to include patients with symptomatic PAD.

Data collection and analysis

Data were extracted by one author (DAL) and checked by the other (GYHL). Eligible studies were excluded when results presentation prevented adequate extraction of data and enquiries to authors did not yield raw data.

Main results

Four studies were included. Two compared ACE inhibitors against placebo. In the HOPE study there was a significant reduction in the number of cardiovascular events in 168 patients receiving ramipril (OR 0.72, 95% confidence interval 0.58 to 0.91). In the second trial using perindopril in a small numbers of patients, there was a marginal increase in claudication distance but no change in ankle brachial pressure index (ABPI) and a reduction in maximum walking distance.

The third trial in patients undergoing angioplasty suggested that the calcium antagonist verapamil reduced restenosis, although this was not reflected in the maintenance of a high ABPI. Another small study 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.

Authors' conclusions

Evidence on various anti‐hypertensive drugs in people with PAD is poor so that it is unknown whether significant benefits or risks accrue from their use. Lack of data specifically examining outcomes in PAD patients should not detract from the compelling evidence of the benefit of treating hypertension and lowering blood pressure.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Treatment of high blood pressure for people with peripheral arterial disease

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) and hypertension are associated with atherosclerosis, which is hardening of the arteries 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 based on the walking distance (on a treadmill) before onset of pain (claudication distance), or ankle brachial pressure index (ABPI). PAD can progress to pain at rest and critical limb ischaemia that requires revascularisation or amputation. Treatment of hypertension, to reduce cardiovascular events and death, needs careful consideration in people with PAD. Anti‐hypertensive medications may worsen the PAD symptoms by 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 examining the risks and benefits of various anti‐hypertensive drug classes on measures of PAD is lacking. We identified four controlled trials in people with symptomatic PAD where participants were randomised to receive an anti‐hypertensive treatment for at least one month, or placebo, or no treatment. In one trial with 397 participants, that the ACE inhibitor, ramipril, was effective in reducing the number of cardiovascular events by 28% compared to placebo. In the other study using an ACE inhibitor, the 26 (48%) patients on perindopril showed a small increase in claudication distance but no change in ABPI and a reduction in maximal walking distance. In patients undergoing peripheral arterial angioplasty (procedure to open narrowed or blocked blood vessels), the results from one trial with 96 participants suggested that the calcium antagonist, verapamil, reduced restenosis at six months. In the fourth small study, peripheral arterial wall thickness was similar whether men received the thiazide diuretic, hydrochlorathiazide, or the alpha‐adrenoreceptor blocker, doxazosin.