Comparative Mortality in Heart Failure on Guideline-Directed Medical Therapy Versus Malignant Cancer: A Report From a Global Federated Research Network.

Background: Guideline-directed medical therapy (GDMT), including angiotensin receptor-neprilysin inhibitor, angiotensin-converting enzyme inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, has significantly improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We examined whether modern GDMT alters the historically observed parity in mortality between HF and cancer.

Methods: From the TriNetX Global Collaborative Research Network (2015-2024), we identified 32 125 patients with HFrEF on GDMT (angiotensin receptor-neprilysin inhibitor or angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, beta blockers, and sodium-glucose cotransporter-2 inhibitors), 403 389 not on full GDMT (not receiving all 4 drugs concurrently), and 2 481 106 with malignant cancers. All-cause mortality was compared between HFrEF and cancer overall and across the most common cancers in men (prostate, colorectal, lung) and women (breast, lung, colorectal) using propensity score matching.

Results: Patients with HFrEF on GDMT with angiotensin receptor-neprilysin inhibitors had significantly better survival than patients with cancer (hazard ratio [HR], 0.44 [95% CI, 0.41-0.47]; P<0.001). A survival benefit, though less pronounced, was also seen for GDMT with angiotensin-converting enzyme inhibitors instead of angiotensin receptor-neprilysin inhibitor (HR, 0.62 [95% CI, 0.57-0.69]; P<0.001). Patients not on GDMT had higher mortality than patients with cancer (HR, 1.15 [95% CI, 1.13-1.17]; P<0.001). Among the most common sex-specific cancers, only patients with prostate and breast cancer had better survival than those with HFrEF on GDMT, whereas patients not on GDMT showed worse outcomes across most cancers, except lung cancer.

Conclusions: In this large real-world analysis, patients with HFrEF on GDMT showed better survival than those with cancer overall and across most sex-specific cancers. Patients not on GDMT experienced worse outcomes, emphasizing the need to optimize treatment in HFrEF.