Prediction of individual CVD-free life-years gained and effect of treatment with decision tool in T2DM
Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitusLiterature - Berkelmans GFN, Gudbjörnsdottir S, Visseren FLJ et al. - European Heart Journal 2019; 0, 1–10
Patients with type 2 diabetes mellitus (T2DM) are at up to two-fold increased risk for CVD, which results in reduced life expectancy and quality-adjusted life years, compared with individuals without T2DM, regardless of other risk factors [1-3]. Although group level effectiveness of recommended medications for prevention of CVD in T2DM has been proven in high-quality trials, important differences in absolute effectiveness are known to exist between individuals.
This study therefore aimed to develop and externally validate a prediction tool for individualizing CVD prevention with lipid-lowering, antihypertensive, glucose-lowering, and aspirin treatment in patients with T2DM, by predicting treatment effects as reductions in 10-year CVD-risk and lifetime risk, and gain in CVD-free life expectancy (time without recurrent MI or stroke).
Methods and results
Development of the DIAL model
The Diabetes Lifetime-perspective prediction (DIAL) model was developed, using data from patients with T2DM registered in the Swedish National Diabetes Registry (NDR) (n=389.366). Two complementary competing risk adjusted Cox proportional hazard functions were developed, one for the prediction of CVD events using non-vascular mortality as the competing endpoint, and another for prediction of non-vascular mortality using CVD events as the competing endpoint.
External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT trials, the SMART and EPIC-NL cohorts, and the Scottish Care Information (SCI) Diabetes database (total n=197.785). This analysis included patients aged >18 years with a diagnosis of T2DM with or without prevalent CVD. Individuals with a history of cancer and those with stage 4 or 5 CKD were excluded. Eleven CVD risk predictors were selected based on existing diabetes risk scores and availability in routine clinical practice: age, sex, smoking, systolic blood pressure, BMI, HbA1c, eGFR, non- HDL-c, albuminuria, T2DM duration, insulin treatment, and history of CVD. Competing outcomes were CVD events (non-fatal MI, non-fatal stoke, or vascular mortality) and non-vascular mortality (all deaths other than those with an identified CV outcome).
Internal validation of the DIAL model
Predicted 10-year risk for CVD and all-cause mortality showed good agreement with the 10-year observed risk, with c-statistics of 0.83 (95%CI: 0.83-0.84) for 10-year CVD risk, 0.72 (95%CI: 0.72-0.72) for 10 year non-vascular mortality risk and 0.77 (95%CI: 0.76-0.77) for 10-year CVD-free survival.
External validation of the DIAL model
Predicted 5-year risks for CVD and all-cause mortality were in good agreement with the observed 5-year CVD-free survival in Western-Europe, Eastern-Europe, North-America, and Asia and Oceania. The C-statistics of the estimated 5-year CVD risk were between 0.64 and 0.65 in all geographically pooled datasets. For 5-year non-vascular mortality, the c- statistics of the different geographical regions varied between 0.59 and 0.67, and between 0.64 and 0.69 for all-cause mortality.
Individual lifetime estimates and treatment effects for people with T2DM
The DIAL model prediction data have been implemented in the interactive online U-Prevent calculator. Patient characteristics and current medication can be entered in this decision support tool to estimate individual risk and CVD-free survival. Also, the individual effect from medication changes can be modelled in terms of CVD-free life-years gained, absolute risk reduction, and individual number needed to treat.
CVD-free life expectancy and effects of lifelong preventive treatment on CVD-free life-years gained can be reliably predicted for patients with T2DM using the DIAL model, which is based on readily available clinical characteristics. The DIAL model is available for use in the online U-Prevent calculator, and may facilitate personalized treatment and support shared decision-making and patients’ motivation to adhere to prescribed drug-treatments to reduce CVD risk.