In a cohort of patients with type 2 diabetes mellitus (T2DM), rates of hospitalization for heart failure (HF), major adverse cardiovascular events (MACE), and all-cause mortality were reduced in new users of dapagliflozin when compared with new users of dipeptidyl peptidase-4 inhibitors (DPP-4i).
Results of the real-world CVD-REAL Nordic trial were presented at the Heart Failure 2017 meeting, held April 29 to May 2 in Paris, France.
For the trial, researchers identified all patients with T2DM who were prescribed glucose-lowering drugs between 2013 and 2016 from the Prescribed Drug Registries and linked them with the National Patient Registry and Cause of Death Registry in Norway and Sweden.
New users were defined as participants with no prescriptions for the drug of interest within 1 year of the drug dispense date. The 2 study groups — new dapagliflozin users (n=8582) and new DPP-4i users (n=25746) — were matched 1:3 by propensity score.
Baseline characteristics of both groups were well matched. The researchers followed patients from drug dispense date to drug discontinuation date, death, or the end of the register.
During follow-up (mean 0.98 years), a total of 33,682 patient-years were reported.
Compared with DPP-4i, dapagliflozin reduced the risk for HF hospitalization (hazard ratio [HR] 0.63; 95% CI, 0.50-0.81 P <.001); MACE (HR 0.71; 95% CI, 0.56-0.90; P =.004); and all-cause mortality (HR 0.73; 95% CI, 0.59-0.91 P =.004).
When analyzed by country, the researchers observed the following differences in cardiovascular complication HRs with dapagliflozin vs DPP-4i:
- HF hospitalization: Norway, 0.65 (95% CI, 0.46-0.92) vs Sweden, 0.62 (95% CI, 0.44-0.88)
- MACE: Norway, 0.62 (95% CI, 0.39-1.00) vs Sweden, 0.74 (95% CI, 0.56-0.97)
- All-cause mortality: Norway, 0.87 (95% CI, 0.65-1.17) vs Sweden, 0.62 (95% CI, 0.46-0.83)
“Multiple sensitivity analyses did not raise concerns of unknown confounding factors,” the researchers noted.
The researchers added that the risk associations for the outcomes were comparable to the EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; ClinicalTrials.gov identifier: NCT01131676) study.
“The present real-world data appear to support effects seen in a randomized clinical trial,” they wrote. “Results from randomized clinical trials (eg, DECLARE-TIMI 58) will be important to elucidate causal relationships.”
Norhammar A, Bodegard J, Nyström T, et al. Dapagliflozin is associated with lower risk of hospitalization for heart failure, major adverse cardiovascular events and all-cause death compared to DPP-4i in T2D patients: CVD-REAL Nordic. Presented at: Heart Failure 2017—The 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris, France.