Time-dependent event accumulation in a cardiovascular outcome trial of patients with type 2 diabetes and established atherosclerotic cardiovascular disease

• Published in: Cardiovascular diabetology Vol. 22; no. 1; p. 72
• Main Authors: Bethel, M Angelyn, Sourij, Harald, Stevens, Susanna R, Hannan, Karen, Lokhnygina, Yuliya, Adler, Amanda I, Peterson, Eric D, Holman, Rury R, Lopes, Renato D
• Format: Journal Article
• Language: English
• Published: England BioMed Central 28-03-2023; BMC
• Subjects: Adjudication; Angina; Angina pectoris; Arteriosclerosis; Atherosclerosis; Atherosclerosis - epidemiology; Cardiovascular diseases; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cardiovascular outcomes; Cerebral infarction; Congestive heart failure; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Efficiency; Estimates; Heart attacks; Hospitalization; Humans; Hypoglycemic Agents - adverse effects; Mortality; Myocardial Infarction; Sitagliptin Phosphate - adverse effects; Stroke; Type 2 diabetes; Cardiovascular outcomes; Myocardial infarction; Type 2 diabetes; Stroke; Adjudication
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-023-01802-x

Estimating cardiovascular (CV) event accrual is important for outcome trial planning. Limited data exist describing event accrual patterns in patients with type 2 diabetes (T2D). We compared apparent CV event accrual patterns with true event rates in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).
Centrally adjudicated event dates and accrual rates for a 4-point major adverse CV event composite (MACE-4; includes CV death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina hospitalization), MACE-4 components, all-cause mortality (ACM), and heart failure hospitalization were compiled. We used three graphical methods (Weibull probability plot, plot of negative log of the Kaplan-Meier survival distribution estimate, and the Epanechnikov kernel-smoothed estimate of the hazard rate) to examine hazard rate morphology over time for the 7 outcomes.
Plots for all outcomes showed real-time constant event hazard rates for the duration of the follow-up, confirmed by Weibull shape parameters. The Weibull shape parameters for ACM (1.14, 95% CI 1.08-1.21) and CV death (1.08, 95% CI 1.01-1.16) were not sufficiently > 1 as to require non-constant hazard rate models to accurately depict the data. The time lag between event occurrence and event adjudication being completed, the adjudication gap, improved over the course of the trial.
In TECOS, the nonfatal event hazard rates were constant over time. Small increases over time in the hazard rate for fatal events would not require complex modelling to predict event accrual, providing confidence in traditional modelling methods for predicting CV outcome trial event rates in this population. The adjudication gap provides a useful metric to monitor within-trial event accrual patterns.
Clinicaltrials.gov NCT00790205.