American College of Cardiology 2018

Nearly 20 000 attendees gathered in Orlando (Fl. USA) in March for the 67th Scientific Sessions of the American College of Cardiology (ACC). There, Dr Gemma Figtree presented a post hoc analysis1 of the Canagliflozin Cardiovascular Assessment Study (CANVAS) program, showing that certain cardiovascular (CV) benefits with the sodium–glucose cotransporter 2 (SGLT-2) inhibitor canagliflozin were greater in patients with a history of heart failure. Canagliflozin reduced the risk for the composite endpoint of CV death or hospitalization for heart failure by 39% relative to placebo among 1461 CANVAS participants with a history of heart failure at baseline (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.46–0.80). Meanwhile, participants without prior heart failure (n = 8681) did not experience a significant risk reduction for this composite endpoint with canagliflozin versus placebo (HR 0.87, 95% CI 0.72–1.06). The P-value for this interaction was significant at 0.021. The full CANVAS population experienced 22% risk reduction for CV death or heart failure hospitalization with canagliflozin versus placebo (HR 0.78, 95% CI 0.67–0.91). There were no significant interactions between heart failure history and three-point major adverse cardiac events (MACE; non-fatal myocardial infarction [MI], non-fatal stroke, or CV death), MI, stroke, all-cause death, or serious decline in renal function. When splitting the study population by heart failure status, enough power was lost such that few significant effects were seen on these endpoints in either cohort individually, but the group with baseline heart failure did retain a statistically significant benefit on all-cause mortality (30% relative risk reduction; HR 0.70, 95% CI 0.51–0.96), whereas the group without baseline heart failure retained a statistically significant benefit on the composite renal endpoint (48% relative risk reduction; HR 0.52, 95% CI 0.37–0.72).

In addition, Dr Mikhail Kosiborod presented results from the Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors (CVD-REAL) 2 trial.2 The real-world CV benefit of SGLT-2 inhibitors observed in the first iteration of CVD-REAL3 extended to the CVD-REAL 2 population representing South Korea (n = 336 644), Japan (n = 67 780), Australia (n = 27 442; only included in the all-cause death analysis), Israel (n = 19 472), Canada (n = 16 064), and Singapore (n = 2726). In CVD-REAL 2, new users of SGLT-2 inhibitors were compared with new users of other glucose-lowering drugs using propensity scores to match 235 065 sets of patients 1:1 in each participating country. In the multinational cohort (n = 470 128), SGLT-2 inhibitors were associated with a 49% risk reduction for all-cause death (HR 0.51, 95% CI 0.37–0.70, P < 0.001 vs other glucose-lowering drugs). The SGLT-2 inhibitors reduced the risk for heart failure hospitalization by 36% (HR 0.64, 95% CI 0.50–0.82, P = 0.001 vs other glucose-lowering drugs). For the composite outcome of all-cause death and heart failure hospitalization, SGLT-2 inhibitors reduced risk by 40% (HR 0.60, 95% CI 0.47–0.76, P < 0.001 vs other glucose-lowering drugs). Dr Kosiborod also presented original CVD-REAL results at the 2017 ACC Scientific Sessions,3 reporting a 51% relative risk reduction for all-cause death with SGLT-2 inhibitors, a 39% relative risk reduction for heart failure hospitalization, and a 46% relative risk reduction for the composite (all P < 0.001).

The Endocrine Society 2018

Nearly 10 000 people gathered in Chicago for the 100th annual meeting of The Endocrine Society in March. Dr Paola Fioretto presented full results from AstraZeneca's (Cambridge, UK) Study to Evaluate the Effect of Dapagliflozin on Blood Glucose Level and Renal Safety in Patients With Type 2 Diabetes (DERIVE), examining the SGLT-2 inhibitor dapagliflozin in type 2 diabetes mellitus (T2DM) and moderate chronic kidney disease (CKD). The DERIVE study (n = 321) randomized adult patients with T2DM and Stage 3A CKD (estimated glomerular filtration rate [eGFR] between 45 and 59 mL/min per 1.73m²) to dapagliflozin 10 mg daily or to placebo for 24 weeks. The primary endpoint was change in HbA1c, which fell from a baseline of 8.3% to 7.9% in the dapagliflozin group (0.37% drop) and stayed almost constant at 8% in the placebo group (0.03% drop). Dr Fioretto reported an estimated treatment difference of 0.34% for HbA1c favoring dapagliflozin (95% CI 0.53%–0.15%, P < 0.001). Dr Fioretto also reported results on the secondary endpoint of body weight, which fell from a baseline of 92 to 89 kg with dapagliflozin and from a baseline of 88 to 86 kg with placebo. She reported an estimated treatment difference of 1.3 kg for body weight change, once again favoring dapagliflozin (P < 0.001). Systolic blood pressure in the group receiving dapagliflozin declined by 4.8 mmHg after just 1 week (baseline 136 mmHg), a level maintained throughout the rest of the trial. Systolic blood pressure decreased by 2 mmHg in the placebo arm from a baseline of 135 mmHg (estimated treatment difference 3.1 mmHg; P < 0.05). There were no imbalances in safety endpoints.