GDMT is Associated with Reduced Loop Diuretic Requirements, Whereas Diuretic Dose Does Not Modify GDMT Benefit in Heart Failure: STRONG-HF.

AIMS: Loop diuretics (LD) are the cornerstone of congestion management in heart failure (HF), but whether their requirement can be reduced by optimizing disease-modifying therapy is unknown. METHODS: In this post-hoc analysis of STRONG-HF (n=1,075 with post-randomization LD data), we assessed whether up-titration of guideline-directed medical therapy (GDMT) lowers LD demand, and whether LD dose reflects HF severity, predicts outcome, or modifies the benefit of high-intensity care. Patients were grouped by furosemide-equivalent dose; change at day 90 was compared by achievement of 100% target GDMT doses. RESULTS: Higher LD doses marked more severe HF. Achieving 100% of target doses of all GDMT classes (RASi, beta-blocker, MRA) translated into a substantially lower diuretic requirement: furosemide-equivalent dose at day 90 fell by -21.94 (SD 52.46) mg versus -1.55 (SD 49.886) mg in those not reaching targets (p<0.001); beta-blockers showed the largest effect of any single class -18.42 (SD 49.61) mg, (p<0.001). LD dose category was not independently associated with the primary endpoint (all-cause death or HF rehospitalization at 180 days) or its components; only LD dose doubling was associated with higher all-cause mortality (adjusted HR 1.47, 95% CI 1.04-2.09), without association with the primary endpoint or rehospitalization (both p>0.05). The benefit of high-intensity care was consistent across LD dose groups (no treatment-by-dose interaction). CONCLUSIONS: GDMT optimization acted as diuretic-sparing therapy: reaching target doses, particularly of all three classes, was associated with markedly lower LD requirement. LD dose mirrored HF severity but neither consistently predicted outcome nor modified the benefit of up-titration.