Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis

Abstract

Aims To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Methods and results Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT’s a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT’s and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l). Conclusions Data from RCT’s and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia. Systematic review registration PROSPERO registration CRD42018089744

Allopurinol

“…A systematic review published in 2021 reported on the effect of allopurinol on cardiovascular mortality, myocardial infarction and stroke in patients with hyperuricaemia and preserved renal function 2 . Of the 26 randomised‐controlled trials included, compared to placebo, allopurinol significantly reduced the combined cardiovascular outcome due to a benefit on myocardial infarction with no significant effect on stroke or cardiovascular mortality.…”

Hyperuricemia: contemporary treatment in patients with cardiovascular disease

“…Важнейшим достоинством является профиль безопасности аллопуринола [67]. Ведь как известно, препарат могут получать даже пациенты, получающие заместительную почечную терапию [68].…”

Impact of Allopurinol on early and one-year outcomes of patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized controlled trial

“…The rst action is increasing local tissue availability of oxygen and adenosine triphosphate by interfering with purine catabolism [8,9]. The second one is reducing uric acid serum concentration, which is pro-in ammatory [10,11]. The third mechanism is inhibiting ROS generation, which promotes endothelial dysfunction and atherosclerosis plaque instability [12,13].…”