Dipeptidyl Peptidase-4 Inhibitors and Cardiovascular Outcomes: Meta-Analysis of Randomized Clinical Trials with 55,141 Participants
Dipeptidyl Peptidase-4 Inhibitors and Cardiovascular Outcomes: Meta-Analysis of Randomized Clinical Trials with 55,141 Participants
复制标题
DOI：
10.1111/1755-5922.12075
复制
发表时间：
2014-08-01
影响因子：
3.1
通讯作者：
Krum, Henry
中科院分区：
文献类型：
--
作者：
Wu, Shiying;Hopper, Ingrid;Krum, Henry
目的：糖尿病患者的血糖降低与主要心血管 (CV) 结局之间的关联较弱；事实上，一些口服降糖药与心血管事件的增加有关。二肽基肽酶 4 抑制剂（DPP-4 抑制剂）是一类新型口服降糖药，可能具有有益的心血管作用。我们进行了系统评价和荟萃分析，以评估 DPP-4 抑制剂的 CV 安全性和有效性。方法：全面搜索涉及 DPP-4 抑制剂的前瞻性试验。试验至少报告一项检查结果，招募至少 100 名患者，随访时间至少为 24 周。使用 Mantel-Haenszel 随机效应模型计算死亡率和主要心血管 (CV) 结局的风险比 (RR)。结果：纳入了 50 项试验，共招募了 55,141 名参与者。平均随访时间为 45.3 周。与所有比较药物（安慰剂和活性药物）相比，DPP-4 抑制剂在全因死亡率（n = 50,982，RR = 1.01，95% CI 0.91-1.13，P = 0.83）、CV 死亡率（n = 48,151，RR = 0.97，95% CI 0.85-1.11，P = 0.83）方面没有差异。 0.70), 急性冠状动脉综合征 (ACS) (n = 53,034 RR = 0.97，95% CI 0.87-1.08，P = 0.59），或卒中（n = 42,737，RR = 0.98，95% CI 0.81-1.18，P = 0.80），心力衰竭结果有统计显着性增加（n = 39,953，RR = 1.16，95% CI 1.01-1.33，P = 0.04）。讨论：与安慰剂相比，DPP-4 抑制剂治疗显示全因死亡率、心血管死亡率、ACS 或中风的风险没有增加，但心力衰竭结局风险有统计学上显着的增加趋势。结论：这些研究结果表明 DPP-4 抑制剂不会对心血管造成损害（或有益）；进一步的大规模心血管结果研究将解决心力衰竭风险过高的问题。
Aims: The association between glucose lowering in diabetes mellitus and major cardiovascular (CV) outcomes is weak; indeed, some oral hypoglycemic agents are associated with increased CV events. Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are a new class of oral hypoglycemic agent that may have beneficial CV effects. We undertook a systematic review and meta-analysis to appraise the CV safety and efficacy of DPP-4 inhibitors. Methods: Comprehensive search for prospective trials involving DPP-4 inhibitors. Trials included reported at least one of the outcomes examined, recruited minimum 100 patients and minimum follow-up 24 weeks. The risk ratio (RR) was calculated using the Mantel-Haenszel random-effects model for mortality and major cardiovascular (CV) outcomes. Results: Fifty trials enrolling 55,141 participants were included. Mean follow-up 45.3 weeks. DPP-4 inhibitors compared with all comparators (placebo and active) showed no difference in all-cause mortality (n = 50,982, RR = 1.01, 95% CI 0.91-1.13, P = 0.83), CV mortality (n = 48,151, RR = 0.97, 95% CI 0.85-1.11, P = 0.70), acute coronary syndrome (ACS) (n = 53,034 RR = 0.97, 95% CI 0.87-1.08, P = 0.59), or stroke (n = 42,737, RR = 0.98, 95% CI 0.81-1.18, P = 0.80), and a statistically significant increase in heart failure outcomes (n = 39,953, RR = 1.16, 95% CI 1.01-1.33, P = 0.04). Discussion: Treatment with DPP-4 inhibitors compared with placebo shows no increase in risk with regards to all-cause mortality, CV mortality, ACS, or stroke, but a statistically significant trend toward increased risk of HF outcomes. Conclusion: These findings suggest no cardiovascular harm (or benefit) with DPP-4 inhibitors; further large-scale CV outcome studies will resolve the issue of excess HF risk.