Greater benefit of SGLT2 inhibitor in type 2 diabetes patients with history of MI

Introduction and methods

Residual CV risk is high in T2DM patient with prior myocardial infarction (MI) despite standard-of-care treatment [1] and robust benefit of major adverse cardiovascular events (MACE) can be achieved with more advanced secondary prevention therapies [2-4]. In addition, patients with history of MI have an increased risk of HF and lower long-term survival [5]. Therefore, there is an unmet need to prevent MACE and HF in T2DM patients with prior MI.

In the DECLARE TIMI-58 trial, T2DM patients with presence of ASCVD or multiple risk factors were randomized to dapagliflozin or placebo on top of standard-of-care medical therapy. Dapagliflozin reduced the composite of CV death and hospitalization for HF, in patients with T2DM (HR 0.83, 95%CI: 0.73 to 0.95, P=0.005). A potential signal of benefit for MACE with dapagliflozin was only observed in those with ASCVD (in total population MACE was not reduced, HR was 0.93, 95%CI: 0.84-1.03, P=0.17) [6]. To examine whether a subgroup of patients with T2DM and prior MI could derive greater benefit from dapagliflozin compared to those without prior MI, a prespecified analysis was performed.

In this prespecified analysis of patients with history of MI (n=3584) vs those without prior MI (n=13576) consisting of those with ASCVD (n=3390) or with multiple risk factors (n=10186), the two primary endpoints were MACE, a composite of CV death, MI or ischemic stroke) and composite of CV death and HF hospitalizations.

Main results

• In patients with prior MI, 15.2% of patients with dapagliflozin vs. 17% in placebo group suffered from MACE (HR 0.84, 95%CI: 0.72-0.99, P=0.039, and absolute risk reduction 2.6%, 95%CI: 0.1-5.0%, NTT over 4 years was 39). In patients without prior MI, there was no reduction in MACE with dapagliflozin compared to placebo group (HR 1.00, 95%CI: 0.88-1.13, P=0.97) (relative P-interaction=0.1, absolute risk reduction P-interaction=0.048). Also, in patients with no prior MI but with established ASCVD, MACE was not reduced in those with dapagliflozin compared to placebo (HR 0.98, 0.81-1.19, P=0.85; absolute risk reduction 0.2%, 95% CI: -2.0 % to 2.4%).
• Relative risk reductions in composite of CV death or HF hospitalizations in patients with and without prior MI were similar (HR 0.81, 95%CI: 0.65-1.00 and HR 0.85, 95%CI: 0.72-1.00, respectively, Pinteraction=0.69). Because patients with prior MI had higher baseline risk, absolute risk reductions were greater with dapagliflozin vs. placebo in these patients (absolute risk reduction of 1.9%, 95%CI: 0.0-3.8%) compared with patients without MI (ARR 0.6%, 95%CI: 0.0-1.3%; absolute risk reduction Pinteraction=0.010). NNT over 4 years was 53.
• Recurrent MI was reduced in patients with prior MI with dapagliflozin use vs. placebo (HR 0.78, 95% CI 0.63-0.95), both type 1 MI (HR 0.80, 95% CI 0.63-1.02) and type 2 MI (HR 0.64, 95% CI 0.42-0.97).
• In those with prior MI, lower rates of the composite of CHD death, non-fatal MI or sudden cardiac death were observed with dapagliflozin vs. placebo (HR 0.81; 95 % CI 0.67-0.97).
• In those with prior MI, reduction of MACE with dapagliflozin was greater the closer patients were to their qualifying MI (Pinteraction trend=0.007).

Conclusion

References

Find this article online at Circulation