HF meds rapid up-titration reduces readmission, mortality after acute HF hospitalization

Rapidly maximizing medications in patients discharged from hospital following acute heart failure (AHF) reduced the risk of hospital readmission or death at 180 days, according to results of the STRONG-HF* trial presented at AHA 2022.

“Rapid up-titration of HF therapies under close follow-up is safe and reduces HF readmissions or all-cause deaths and improves patients’ quality of life (QoL),” said study author Professor Alexandre Mebazaa from the Université de Paris and Assistance Publique Hôpitaux de Paris in Paris, France.

The study participants were 1,078 patients (median age 63 years, 61 percent male, 77 percent White) who were ready for discharge following hospitalization for AHF and who had pre-discharge NT-proBNP** levels >1,500 pg/mL. They were randomized 1:1 to receive either usual care (as per local practice) or high-intensity care (beta-blockers, ACE*** inhibitors/ARBs***/ARNIs***, and MRAs*** rapidly up-titrated to 50 percent of optimal doses pre-discharge and to 100 percent within 2 weeks post-discharge). 

Mean baseline NT-proBNP was 4,121 and 3,929 pg/mL in the high-intensity and usual care groups, respectively, and systolic blood pressure 123 and 122 mm Hg, respectively. Almost 30 percent of patients had diabetes and >40 percent had atrial fibrillation.

The risk of readmission for HF or all-cause death at 180 days was significantly reduced among patients assigned to the high-intensity intervention vs usual care (treatment effect, 8.1 percent, 95 percent confidence interval, 2.9–13.2; p=0.0021). [AHA 2022, session FS.04]

The results were consistent in the subgroups analysed including left ventricular ejection fraction (LVEF; risk difference, 6.3 and 12.5 percent for LVEF ≤40 and >40 percent, respectively; p_interaction=0.27) and NT-proBNP level at baseline (risk difference, 3.7 and 13.2 percent for ≤ and > median level, respectively; p_interaction=0.08).

At day 90, the high-intensity intervention improved all congestion parameters compared with usual care namely weight (adjusted treatment effect [adjTE], –1.36 kg; p<0.0001), respiratory rate (adjTE, –0.4 breaths/min; p=0.0028), peripheral oedema grade (adjTE, 1.30; p=0.0002), jugular venous pressure (adjTE, 1.13 cm; p=0.015), New York Heart Association class (adjTE, 1.36; p<0.0001), and NT-proBNP level (adjTE, 0.77 pg/mL; p=0.0003).

QoL, as per EQ-5D visual analogue scale, at 90 days was also improved with the high-intensity intervention vs usual care (treatment effect, 3.5; p<0.0001). This suggests that the benefits of rapid up-titration of medications extend beyond the readmission and mortality improvements, said Mebazaa.

At day 90, treatment-emergent adverse events (TEAEs) were documented in 41.1 and 29.5 percent of patients in the high-intensity intervention and usual care groups, respectively, with a comparable rate between groups in terms of serious TEAEs (16.2 percent vs 17.2 percent) and fatal serious TEAEs (4.6 percent vs 6.0 percent).

“The American Heart Association and the European Society of Cardiology both recommend that patients hospitalized with AHF should receive optimal doses of three main classes of HF medicine (beta-blockers, renin-angiotensin inhibitors/ARNIs, and aldosterone inhibitors) and regular follow-up visits post-discharge,” said Mebazaa.

“However, low implementation of guideline-directed medical therapies has been a major problem for decades, and previous studies have found that optimal doses of these medications are only administered in 1 percent of HF patients in the US. Some studies also suggest that women are less likely than men to receive optimal therapy,” he continued.

“The high-intensity care strategy required an average of five visits within 3 months post-discharge, compared with one visit in usual care,” said Mebazaa. “Other reasonably sized and powered studies have examined intense follow-up, however, there was no impact on death rates or hospital readmission. More follow-up visits alone do not appear effective without rapidly increasing guideline-directed medicines to maximally tolerated doses,” he pointed out.

The study was prematurely terminated due to the larger-than-expected between-group difference in the primary endpoint, where it was deemed unethical to keep patients in usual care, said Mebazaa.