Abstract
Background: Event accumulation patterns in event-driven trials inform forecasting of trial size and duration. It is hypothesized that trials enrol a healthier cohort who have lower early cardiovascular (CV) event rates that increase during follow-up as surviving patients age and accumulate comorbidities. We present hazard rate patterns for incident CV events in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods: Using adjudicated endpoints from the intention-to-treat population, Weibull models show whether hazards for these CV events were increasing (shape parameter>1), decreasing (<1), or constant (=1) over time: MACE-4 composite (CV death, nonfatal myocardial infarction [NFMI], nonfatal stroke [NFSt], and unstable angina hospitalization [UA]); fatal (F) or NFMI, F/NFSt, UA, CV death, all-cause mortality (ACM), and heart failure hospitalization (HF). Results: The Figure shows hazard rate over time. Weibull shape point estimates (95% CI) were MACE-4 0.96 (0.92, 1.01); ACM 1.14 (1.08, 1.21); CV death 1.(1.01, 1.16); F/NFMI 0.96 (0.89, 1.03); F/NFSt 0.93 (0.85, 1.03); UA 0.90 (0.79, 1.01); HF 0.98 (0.90, 1.08). Annual event rates (per 100 pt-years) were CV death: 1.5, 1.6, 2.0, 1.9, 2.7; ACM: 2.1, 2.3, 2.8, 3.0, 3.8. Conclusions: Hazard rates were constant for all events except CV death and ACM, which had small significant increased risk over time. Our findings may inform the planning and conduct of future trials in diabetes. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc.. S.R. Stevens: None. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A. Adler: None. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. E. Peterson: Research Support; Self; Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.
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