OBJECTIVES: The public health burden of heart failure has a higher incidence and disproportionally presents at a younger age in Asian populations compared to other racial and ethnic groups. We thus aimed to evaluate the treatment efficacy of different heart failure pharmacological interventions on Asian vs. White patients with heart failure with reduced ejection fraction (HFrEF).

METHODS: We conducted a pairwise meta-analysis of RCTs in adults with HFrEF. We searched articles in Embase, PubMed, and Cochrane Central Register of Controlled Trials from inception to Feb 9, 2022 and identified RCTs investigating the efficacy of heart failure drugs, including angiotensin converting enzyme inhibitors (ACEi), sacubitril/valsartan (ARNi), beta-blockers (BB), hyperpolarization-activated cyclic nucleotide-gated channel blockers (HCNCB), sodium-glucose cotransporter 2 inhibitors (SGLT2i), renin inhibitors, vasopressin V2 receptor blockers (VRA), and oral soluble guanylate cyclase (sGC) stimulators. The outcome was a composite endpoint of hospitalization for heart failure (HHF), cardiovascular death, and all-cause death.

RESULTS: We included 11 RCTs involving 32,654 participants of Asian and White races. In Asian patients, SGLT2i (RR, 0.61; 95%CI, 0.49-0.75) was the most effective for reducing the composite endpoint of HHF, cardiovascular death, and all-cause death, followed by HCNBC (RR, 0.62; 95%CI, 0.42-0.89). In White patients, BB (RR, 0.68; 95%CI, 0.59-0.78) was most effective for lowering the risk of adverse outcomes, followed by ACEi (RR, 0.81; 95%CI, 0.71-0.93). Overall, SGLT2i is the most effective treatment in reducing the risk of adverse outcomes among all patients with HFrEF (RR, 0.72; 95%CI, 0.53-0.97), but have a better treatment effect in Asian patients (RR,0.61; 95%CI, 0.49-0.75) compared to their White counterparts (RR, 0.83; 95%CI, 0.74-0.93) (P_interaction= 0.014).

CONCLUSIONS: The SGLT2i treatment was effective in lowering the risk of adverse clinical outcomes in patients with HFrEF for both Asian and White populations, while it appeared to be more effective in the Asian patient population.