Robert Wilcox1, Stuart Kupfer, Erland Erdmann. 1. Department of Cardiovascular Medicine, Queen's Medical Centre, University Hospital, Nottingham, United Kingdom. robert.wilcox@nottingham.ac.uk
Abstract
BACKGROUND: Composite end points of major adverse cardiovascular events (MACEs) are standard measures for comparing treatment in large cardiovascular outcome studies. This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes. METHODS: PROactive was a cardiovascular outcome study that randomized patients with type 2 diabetes topioglitazone (n = 2605) or placebo (n = 2633), in addition to existing glucose-lowering and cardiovascular medications. Pioglitazone was titrated from 15 to 45 mg/d based upon tolerability. Mean follow-up was 34.5 months. RESULTS: At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83. CONCLUSIONS: In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years.
RCT Entities:
BACKGROUND: Composite end points of major adverse cardiovascular events (MACEs) are standard measures for comparing treatment in large cardiovascular outcome studies. This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes. METHODS: PROactive was a cardiovascular outcome study that randomized patients with type 2 diabetes to pioglitazone (n = 2605) or placebo (n = 2633), in addition to existing glucose-lowering and cardiovascular medications. Pioglitazone was titrated from 15 to 45 mg/d based upon tolerability. Mean follow-up was 34.5 months. RESULTS: At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83. CONCLUSIONS: In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years.
Authors: Lawrence H Young; Catherine M Viscoli; Jeptha P Curtis; Silvio E Inzucchi; Gregory G Schwartz; Anne M Lovejoy; Karen L Furie; Mark J Gorman; Robin Conwit; J Dawn Abbott; Daniel L Jacoby; Daniel M Kolansky; Steven E Pfau; Frederick S Ling; Walter N Kernan Journal: Circulation Date: 2017-02-28 Impact factor: 29.690
Authors: Jin Xu; Catherine M Viscoli; Gary A Ford; Mark Gorman; Walter N Kernan Journal: J Stroke Cerebrovasc Dis Date: 2016-04-11 Impact factor: 2.136
Authors: Carmella Evans-Molina; Reiesha D Robbins; Tatsuyoshi Kono; Sarah A Tersey; George L Vestermark; Craig S Nunemaker; James C Garmey; Tye G Deering; Susanna R Keller; Bernhard Maier; Raghavendra G Mirmira Journal: Mol Cell Biol Date: 2009-02-23 Impact factor: 4.272
Authors: Michael J Cairelli; Christopher M Miller; Marcelo Fiszman; T Elizabeth Workman; Thomas C Rindflesch Journal: AMIA Annu Symp Proc Date: 2013-11-16