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SGLT2 inhibitors cut risk of heart failure, death

Stephen Padilla
04 Sep 2019

Use of sodium glucose cotransporter 2 (SGLT2), as compared with dipeptidyl peptidase 4 (DPP4), inhibitors appears to reduce the risk of heart failure and any-cause death without major cardiovascular events in the primary intention-to-treat analysis, according to a study.

“In the additional as-treated analyses, the magnitude of the association with heart failure and any-cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed,” the researchers said.

This cohort study obtained data from nationwide registers in Denmark, Norway and Sweden from April 2013 to December 2016. In total, 20,983 new users of SGLT2 inhibitors and 20,983 new users of DPP4 inhibitors (mean age, 61 years; 60 percent men; 19 percent had a history of major cardiovascular disease [CVD]) were included and matched by age, sex, major CVD history and propensity score.

Major CV events (composite of myocardial infarction, stroke and CV death) and heart failure (hospital admission for or death due to heart failure) were the primary outcomes. Secondary outcomes included individual components of the CV composite and any-cause death.

Patients were defined as exposed from treatment initiation throughout follow-up in the primary analyses. Additional analyses were performed with an as-treated exposure definition. Hazard ratios (HRs) were calculated using Cox regression.

Among users of SGLT2 inhibitors, 22,627 (83 percent) initiated dapagliflozin, 4,521 (16 percent) received empagliflozin, and 268 (1 percent) were administered canagliflozin.

During follow-up, a major CV event occurred in 467 SGLT2 inhibitor users (incidence rate, 17.0 events per 1,000 person-years) and in 662 DPP4 inhibitor users (18.0), while a heart failure event occurred in 130 (4.7) and 265 (7.1), respectively. HRs for major CV events and heart failure were 0.94 (95 percent CI, 0.84–1.06) and 0.66 (0.53–0.81), respectively. HRs were consistent among subgroup of patients with and without history of major CVD and heart failure. [BMJ 2019;366:l4772]

For secondary outcomes, SGLT2 compared with DPP4 inhibitors had HRs of 0.99 (0.85–1.17) for myocardial infarction, 0.94 (0.77–1.15) for stroke, 0.84 (0.65–1.08) for CV death and 0.80 (0.69–0.92) for any-cause death.

As-treated analyses revealed HRs of 0.84 (0.72–0.98) for major CV events, 0.55 (0.42–0.73) for heart failure, 0.93 (0.76–1.14) for myocardial infarction, 0.83 (0.64–1.07) for stroke, 0.67 (0.49–0.93) for CV death and 0.75 (0.61–0.91) for any-cause death.

“These data help inform patients, practitioners and authorities regarding the CV effectiveness of SGLT2 inhibitors in routine clinical practice,” the researchers said.

Several cohort studies, although limited by their designs, have also reported the association of SGLT2 inhibitors with a reduced risk of CV events and death. [Circulation 2017;136:249-259; Lancet Diabetes Endocrinol 2017;5:709-701; J Am Coll Cardiol 2018;71:2628-2639; Diabetes Obes Metab 2018;20:344-351; Circulation 2018;137:1450-1459]

The current study was limited by its observational design and the absence of randomization, which could have resulted in residual confounding, according to the researchers.

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