The real-world use of benefit-unproven ARBs in HFrEF: clinical outcomes and prescription patterns
J Park, D K Kim, J H ChoiAbstract
Background
In the contemporary landscape of heart failure (HF) management, angiotensin II receptor blockers (ARBs) remain widely used despite the advent of angiotensin receptor–neprilysin inhibitors. Among available ARBs, only valsartan, candesartan, and losartan have demonstrated clinical benefit in patients with heart failure with reduced ejection fraction (HFrEF; LVEF <40%) (hereafter, benefit-proven ARBs). The clinical outcomes associated with other ARBs in HFrEF (benefit-unproven ARBs) remain uncertain.
Purpose
To describe real-world ARB prescription patterns in HFrEF and compare clinical outcomes between benefit-proven and benefit-unproven ARBs.
Methods
Using the National Health Insurance Service database, we identified adult patients with HFrEF receiving guideline-directed background therapy (renin–angiotensin system inhibitor [RASi], beta-blocker, mineralocorticoid receptor antagonist, and loop diuretic) between January 2008 and December 2015. We compared the incidence of a 5-year composite outcome (all-cause death, HF hospitalization, or heart transplantation) between patients prescribed benefit-unproven ARBs (eprosartan, fimasartan, irbesartan, olmesartan, and telmisartan) and those receiving benefit-proven ARBs.
Results
A total of 3,879 HFrEF patients receiving background therapy were included (mean age 57.8±13.7 years; 67.8% male). Among 2,731 ARB prescriptions, candesartan (860, 31.5%), valsartan (800, 29.3%), and losartan (451, 16.5%) were most common, followed by telmisartan (228, 8.3%), irbesartan (147, 5.4%), olmesartan (140, 5.1%), fimasartan (68, 2.5%), and eprosartan (37, 1.4%). Compared with benefit-proven ARBs, irbesartan (HR 0.85, 95% CI 0.57–1.29; p=0.452), olmesartan (HR 0.75, 95% CI 0.48–1.16; p=0.193), and telmisartan (HR 1.04, 95% CI 0.76–1.43; p=0.819) were not associated with a significant difference in the composite outcome. Fimasartan was associated with a lower risk of the composite outcome (HR 0.49, 95% CI 0.24–1.00; p=0.049).
Conclusion
A substantial proportion of HFrEF patients in real-world practice receive benefit-unproven ARBs. Overall, these agents were not associated with worse clinical outcomes compared with benefit-proven ARBs. Benefit-unproven ARBs may be considered in selected scenarios when benefit-proven ARBs or other renin–angiotensin system inhibitors are not feasible.For image description, please refer to the figure legend and surrounding text.Cox regression: composite outcomeFor image description, please refer to the figure legend and surrounding text.