van der Pol Karel H, Wever Kimberley E, Verbakel Mariette, Visseren Frank L J, Cornel Jan H, Rongen Gerard A
Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands.
Department for Health Evidence, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands.
PLoS One. 2021 Dec 2;16(12):e0260844. doi: 10.1371/journal.pone.0260844. eCollection 2021.
To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.
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).
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.
PROSPERO registration CRD42018089744.
比较别嘌醇与不治疗或安慰剂在预防高尿酸血症患者心血管事件方面的有效性。
检索了从创刊至2020年7月的PubMed、Web of Science和Cochrane图书馆。纳入了对无严重肾脏疾病的高尿酸血症患者进行别嘌醇治疗与安慰剂或不治疗的随机对照试验（RCT）和观察性研究。观察指标为心血管死亡率、心肌梗死、中风或综合终点（CM/MI/S）。对于RCT进行随机效应荟萃分析。对于观察性研究进行叙述性综合分析。在最初的1995篇参考文献中，我们最终纳入了26项RCT和21项观察性研究。我们发现，与对照组相比，别嘌醇组综合终点风险显著降低（风险比0.65[95%CI][0.46至0.91]；p = 0.012），心肌梗死风险降低（RR 0.47[0.27至0.80]；p = 0.01）。我们发现别嘌醇对中风或心血管死亡率无显著影响。在15项质量足够的观察性研究中，在报告该结果的3项研究中有1项显示别嘌醇与心血管死亡率降低相关，在8项研究中有6项显示与心肌梗死降低相关，在7项研究中有4项显示与中风降低相关，在2项研究中有2项显示与综合终点降低相关。仅当别嘌醇治疗延长超过6个月且给予适当的别嘌醇剂量（300毫克或更多/天）或血清尿酸盐浓度充分降低（<0.36毫摩尔/升）时，才观察到心血管获益。
RCT和观察性研究的数据表明，别嘌醇治疗可降低高尿酸血症患者的心血管风险。然而，RCT的证据质量为低到中等。为确定别嘌醇是否能降低心血管事件风险，需要在高风险高尿酸血症患者中进行设计良好且有足够效力的随机、安慰剂对照试验。
PROSPERO注册编号CRD42018089744。
