Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial.
Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial.
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DOI：
10.1016/s0140-6736(12)61190-8
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发表时间：
2012-08-11
期刊：
影响因子：
168.9
通讯作者：
Glynn, Robert J.
中科院分区：
文献类型：
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作者：
Ridker, Paul M.;Pradhan, Aruna;MacFadyen, Jean G.;Libby, Peter;Glynn, Robert J.
由于他汀类药物治疗会增加患糖尿病的风险，因此这些药物一级预防的获益与风险的平衡已引起争议。我们对 JUPITER 试验的参与者进行了分析，以解决使用他汀类药物的血管益处和糖尿病风险之间的平衡问题。在随机、双盲 JUPITER 试验中，17,603 名既往没有心血管疾病或糖尿病的男性和女性被随机分配到瑞舒伐他汀 20 mg 组或安慰剂组，并针对试验主要终点（心肌梗死、中风、不稳定心绞痛住院、动脉血运重建或心血管死亡）和方案预先指定的次要终点（静脉血栓栓塞）进行长达 5 年的随访。 血栓栓塞 (VTE)、全因死亡率和糖尿病事件。为了平衡血管益处和糖尿病风险，参与者根据不存在或至少存在以下一种糖尿病主要危险因素进行分层：代谢综合征、空腹血糖受损、体重指数 > 30 kg/m2 或 HbA1c > 6%。具有一种或多种主要糖尿病危险因素的试验参与者 (N=11,508) 患糖尿病的风险较高；对于此类个体，他汀类药物分配与主要终点降低 39% (P=0.0001)、VTE 降低 36% (P=0.08)、总死亡率降低 17% (P=0.15) 以及糖尿病发病率增加 28% (P=0.01) 相关。因此，对于那些有糖尿病危险因素的人来说，每 54 例新诊断的糖尿病病例就可以避免 93 例血管事件或死亡。对于没有主要糖尿病危险因素的试验参与者 (N=6,095)，他汀类药物分配与主要终点降低 52% (P=0.0001)、VTE 降低 53% (P=0.05)、总死亡率降低 22% (P=0.08) 以及糖尿病发病率没有增加相关 (HR 0.99，P=0.99)。对于这些人来说，总共避免了 86 起血管事件或死亡，并且没有诊断出新的糖尿病病例。在仅限于随访期间患糖尿病的 486 名参与者的分析中（瑞舒伐他汀组 270 名，安慰剂组 216 名，P=0.01），与他汀类药物治疗相关的心血管风险降低的点估计（风险比 0.63）与整个试验中观察到的结果一致（风险比 0.56）。与安慰剂相比，他汀类药物的分配使糖尿病诊断的平均时间缩短了 5.4 周。在 JUPITER 一级预防试验中，他汀类药物治疗对心血管和死亡率的益处超过了糖尿病的风险，包括那些患糖尿病风险较高的人
As statin therapy increases risks of diabetes, the balance of benefit and risk in primary prevention for these agents has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use. In the randomized, double-blind JUPITER trial, 17,603 men and women without prior cardiovascular disease or diabetes were randomly allocated to rosuvastatin 20 mg or placebo and followed for up to 5 years for the trial primary endpoint (myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death) and the protocol pre-specified secondary endpoints of venous thromboembolism (VTE), all-cause mortality, and incident diabetes. To address balance of vascular benefits and diabetes hazard, participants were stratified on the basis of having none or at least one of the following major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body mass index >30 kg/m2, or HbA1c > 6 percent. Trial participants with one or more major diabetes risk factor (N=11,508) were at higher risk of developing diabetes; for such individuals, statin allocation was associated with a 39 percent reduction in the primary endpoint (P=0.0001), a 36 percent reduction in VTE (P=0.08), a 17 percent reduction in total mortality (P=0.15) and a 28 percent increase in diabetes (P=0.01). Thus, for those with diabetes risk factors, 93 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factor (N=6,095), statin allocation was associated with a 52 percent reduction in the primary endpoint (P=0.0001), a 53 percent reduction in VTE (P=0.05), a 22 percent reduction in total mortality (P=0.08) and no increase in diabetes (HR 0.99, P= 0.99). For such individuals, a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed. In analysis limited to the 486 participants who developed diabetes during follow-up (270 on rosuvastatin vs. 216 on placebo group, P=0.01), the point estimate of cardiovascular risk reduction associated with statin therapy (hazard ratio 0.63) was consistent with that observed for the trial as a whole (hazard ratio 0.56). As compared to placebo, statin allocation accelerated the average time to diagnosis of diabetes by 5.4 weeks. In the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including among those at higher risk for developing diabetes