Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE-TIMI 58 trial: A nationwide observational study - PubMed (original) (raw)

Observational Study

. 2019 May;21(5):1136-1145.

doi: 10.1111/dom.13627. Epub 2019 Feb 6.

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Observational Study

Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE-TIMI 58 trial: A nationwide observational study

Anna Norhammar et al. Diabetes Obes Metab. 2019 May.

Abstract

Aims: To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose-lowering drugs (GLDs) in a real-world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE-TIMI 58 study.

Methods: Patients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE-TIMI 58 inclusion criteria: age ≥40 years and established CV disease or presence of multiple-risk factors, e.g. men aged ≥55 years and women aged ≥60 years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE-TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV-specific mortality, and major adverse CV events (MACE; CV-specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs).

Results: After matching, a total of 28 408 new-users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE-like cohort. The mean age of this cohort was 66 years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69-0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79-1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67-0.93) and HR 0.75 (95% CI 0.57-0.97), respectively. Non-significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74-1.11) and HR 1.06 (95% CI 0.87-1.30), respectively.

Conclusion: In a real-world population similar to those included in the DECLARE-TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs.

Keywords: cardiovascular disease; cohort study; dapagliflozin; pharmaco-epidemiology; type 2 diabetes.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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Conflict of interest statement

Author contributions

All authors participated in the research design. M.T. performed the data management and statistical analyses after discussion with all authors. All authors participated in data interpretation and in writing the manuscript. All authors took responsibility for the decision to submit for publication.

Figures

Figure 1

Figure 1

Flow charts for dapagliflozin versus other glucose‐lowering drug (GLD) groups. Proportions not fulfilling propensity‐matching 1:3 with 0.2 caliper were excluded and shown in grey boxes

Figure 2

Figure 2

Correlation between baseline established cardiovascular disease (eCVD) and all‐cause mortality rates in the comparator groups from populations with multiple risk factors (MRF) and eCVD in a real‐world DECLARE‐like vs clinical trial setting. References: Neal et al NEJM 20173; Zinman et al NEJM 20154; Wiviott et al NEJM 20185, ER, event rates, events per 1000 patient‐years

Figure 3

Figure 3

Forest plots comparing the real‐world DECLARE‐like results with those of other sodium‐glucose co‐transporter‐2 inhibitor cardiovascular outcome trials. The studies are presented according to mortality event rates in the comparator group, that is, highest in EMPA‐REG OUTCOME and lowest in DECLARE‐TIMI 58. References: Fitchett et al Eur Heart J 201836; Radholm et al Circulation 201837; Wiviott et al NEJM 20185. CV, cardiovascular; ER, event rate per 1000 patient‐years; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events (CV‐specific mortality, non‐fatal myocardial infarction and non‐fatal stroke)

Figure 4

Figure 4

Forest plots comparing results from intention‐to‐treat (ITT) vs an on‐treatment (OT) analysis. CV, cardiovascular; ER, event rate per 1000 patient‐years; HHF, hospital event for heart failure; MACE, major adverse cardiovascular events (CV‐specific mortality, non‐fatal myocardial infarction and non‐fatal stroke)

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