Risk equations (RE) from the UK Prospective Diabetes Study (UKPDS) remain the most commonly used within economic models of type 2 diabetes mellitus (T2DM). However, clinical practice has evolved since UKPDS reported and the applicability of these RE to contemporary T2DM patients is uncertain. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial assessed cardiovascular (CV) outcomes in a broad T2DM population treated with dapagliflozin (DAPA) versus placebo (PLA). This study aimed to assess the performance of the UKPDS 82 RE in the DECLARE-TIMI 58 population. RE for myocardial infarction (MI), heart failure (HF) and stroke were applied to baseline characteristics and 12-month effects of DAPA versus PLA on HbA1c, weight and blood pressure from DECLARE-TIMI 58. Predicted annual probabilities were converted to event rates per 1,000-person years and associated relative risks (RR) for DAPA versus PLA derived for comparison to trial outcomes. Due to misalignment of the UKPDS and DECLARE-TIMI 58 endpoints, predictions of congestive heart failure were compared to observed incidence of hospitalization for HF and stroke to ischemic stroke, respectively. Predicted (study reported) rates per 1,000 person years for MI, HF and stroke were 8.15 (11.7), 2.47 (6.20) and 3.28 (6.90) for DAPA, and 8.53 (13.2), 2.59 (8.50) and 3.46 (6.80) for PLA. Predicted RR of MI, HF and stroke for DAPA versus PLA were 0.96, 0.95, 0.95, respectively, compared to reported hazard ratios of 0.89 (95% CI: 0.77, 1.01), 0.73 (0.61, 0.88) and 1.01 (0.84, 1.21) in DECLARE-TIMI 58. UKPDS 82 RE did not predict the reduction in CV events demonstrated for DAPA versus PLA based on risk factor improvements observed in DECLARE-TIMI 58. These findings add to a growing body of evidence that suggests the CV effects of sodium-glucose co-transporter inhibitors such as DAPA cannot be fully described via treatment-induced changes in conventional prognostic factors.
P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca.