Leveraging a Bayesian Approach in a Comparative Effectiveness Trial of Major Adverse Cardiovascular Events.

Area of Science:

• Cardiology
• Pharmacology
• Biostatistics

Background:

• Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are increasingly used for managing type 2 diabetes and heart failure.
• The cardiovascular benefits of SGLT2i are well-established, but precise quantification, especially with prior clinical information, requires advanced statistical methods.

Purpose of the Study:

• To investigate the association of SGLT2 inhibitors (SGLT2i) with the composite outcome of Major Adverse Cardiovascular Event and Heart Failure hospitalization (MACE+HF) and its components using a Bayesian approach.
• To leverage Bayesian methods for incorporating prior clinical data and generating probability statements on the protective effects of SGLT2i.

Main Methods:

• Applied a Bayesian time-to-event model with covariates in the hazard function.
• Utilized propensity score matching and fitted three models: Uninformative prior, informative prior from a meta-analysis of cohorts with no prior cardiovascular disease (No CVD), and informative prior from cohorts with prior CVD (CVD).
• Estimated posterior distributions for hazard ratios (HR) using Hamiltonian Monte Carlo, calculating the probability of a meaningful protective association (HR < 0.90).

Main Results:

• Bayesian models indicated a protective association for SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for MACE+HF across priors: No CVD HR 0.82 (0.68, 0.96), CVD HR 0.82 (0.71, 0.94), Uninformative HR 0.79 (0.65, 0.94).
• Probabilities of a meaningful protective association were high: No CVD 88%, CVD 92%, Uninformative 93%.
• Specific components showed strong protection: Heart Failure hospitalization (95%), CVD death (93%), with CVD hospitalization at 67%.

Conclusions:

• Bayesian analysis effectively incorporated prior information to assess SGLT2i's association with MACE+HF components.
• This approach provides an interpretable measure: the probability of a meaningful protective association, enhancing understanding of SGLT2i's cardiovascular benefits.