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Dipeptidyl Peptidase‐4 Inhibitors and Cardiovascular Outcomes: Meta‐Analysis of Randomized Clinical Trials with 55,141 Participants

2014; Wiley; Volume: 32; Issue: 4 Linguagem: Inglês

10.1111/1755-5922.12075

1755-5922

Shiying Wu, Ingrid Hopper, Marina Skiba, Henry Krum,

Neuroendocrine Tumor Research Advances

Abstract 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 M antel– H aenszel 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.