Efficacy and safety of rapid up-titration of medical therapies for heart failure by ischemic and non-ischemic etiologies: an analysis of STRONG-HF

Background Patients with acute heart failure (HF) have differing phenotypes based on ischemic or non-ischemic HF etiology. Rapid up-titration of guideline-directed medical therapy (GDMT) could improve outcomes but understanding differences in efficacy and safety by HF etiology is necessary. Purpose The efficacy and safety of intensive up-titration of GDMT among patients with ischemic and non-ischemic HF etiologies was compared. Methods STRONG-HF was a multinational, randomized trial enrolling patients aged 18-85 years with acute HF hospitalization. Patients were randomized to high intensity versus usual care. High intensity care consisted of GDMT titration to maximal doses within two weeks of hospital discharge. Patients with intolerance to beta blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARBs) were excluded. Usual care consisted of standard physician practice at each site. GDMT consisted of beta blockers, ACEi/ARBs/angiotensin receptor-neprilysin inhibitors (ARNis), and mineralocorticoid receptor antagonists (MRAs). Patients were stratified by ischemic or non-ischemic HF etiology. The primary endpoint was 180-day readmission for HF or all-cause death. Safety endpoints included changes in vital signs and laboratory measurements, as well as adverse events. Results A total of 514 (47.8%) and 561 (52.2%) patients in STRONG-HF had ischemic and non-ischemic HF etiology, respectively. Greater increases in beta blocker, ACEi/ARB/ARNi, and MRA use were observed by 90 days with intensive vs standard care in both patients with ischemic etiology (beta blocker: 86.8% vs 21.3%; ACEi/ARB/ARNi: 84.6% vs 24.1%; MRA: 58.1% vs 26.4%) and non-ischemic HF etiology (beta blocker: 89.1% vs 15.4%; ACEi/ARB/ARNi: 89.1% vs 12.6%, MRA: 55.1% vs 16.1 %). High-intensity compared with usual care reduced HF readmission or all-cause death by 180 days (adjusted hazard ratio [aHR]: 0.61 [95% CI: 0.44, 0.85]), without differences by ischemic (aHR: 0.69 [95% CI: 0.46, 1.05]) or non-ischemic HF etiology (aHR: 0.50 [95% CI: 0.29, 0.85]) (Pinteraction[int]=0.34) (Table 1, Figure 1). Similar findings were observed for HF readmission by 180 days for ischemic vs non-ischemic HF etiology (aHR: 0.56 [95% CI: 0.33, 0.95] vs aHR: 0.44 [95% CI: 0.22, 0.85], Pint=0.56). Mean eGFR changes between high intensity and usual care were similar by ischemic etiology (-0.23 [95% CI: -2.95, 2.49]) and non-ischemic etiology HF (-0.03, [95% CI: -2.55, 2.49]) (Pint=0.92). Other vital signs and labs changes, as well as adverse, serious adverse, and fatal adverse event rates were similar irrespective of treatment group or HF etiology. Conclusions Intensive titration of GDMT within two weeks of discharge was effective and safe, with similar findings among patients with ischemic and non-ischemic etiologies of HF. Intensive GDMT titration protocols could significantly improve HF management.