What is the effect on cardiovascular events of reducing hyperuricemia with allopurinol? An evidence-based review.

INTRODUCTION High levels of uric acid (UA) have been associated with cardiovascular (CV) disease, but its role as an independent risk factor is the subject of debate. Treating hyperuricemia may be useful in reducing CV risk. OBJECTIVE To review the evidence on the effect of treatment with allopurinol in patients with hyperuricemia on reducing CV events. METHODS We searched medical databases for randomized controlled trials (RCT), cohort studies (CS) and case-control studies (CCS), meta-analyses, systematic reviews and guidelines, published between January 2002 and December 2013 in Portuguese and English. Level of evidence (LE) and strength of recommendation were graded according to the definitions used by the European Society of Cardiology. RESULTS Out of 46 articles, one RCT, three CS and one CCS were included. In the RCT, treatment with allopurinol decreased CV events in patients with moderate chronic renal failure by 71% compared to controls (LE B). In one CS, patients treated with high doses had a greater reduction in CV events compared to low doses (LE B). The other two CS, in patients with heart failure (HF), found similar benefits in patients treated with high doses of allopurinol (LE B). In the CCS, in patients with HF and a history of gout, treatment with allopurinol reduced HF admission and all-cause mortality (LE B). DISCUSSION AND CONCLUSIONS Prolonged treatment with high doses of allopurinol may be associated with a reduction in morbidity and mortality in high CV risk populations (class of recommendation IIa). More studies evaluating the effect of therapy with allopurinol in reducing CV events in patients with and without risk are needed.