This summary is based on the publication of Chioncel O et al. - Non-cardiac comorbidities and intensive up-titration of oral treatment in patients recently hospitalized for heart failure: Insights from the STRONG-HF trial. Eur J Heart Fail. 2023 Sep 20. doi: 10.1002/ejhf.3039.

Introduction and methods

Background

Observational studies have demonstrated that in patients with acute HF (AHF), non-cardiac comorbidities are common and are associated with increased mortality and morbidity risks [1,2]. The STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies) trial recently showed that high-intensity care (HIC) improved quality of life and reduced the risk of 180-day all-cause mortality or HF rehospitalization compared with usual care [3].

Aim of the study

In a STRONG-HF analysis, the authors assessed the potential interaction between non-cardiac comorbidities and the feasibility, efficacy, and safety of HIC versus usual care in patients hospitalized for AHF.

Methods

The STRONG-HF trial was an international, multicenter, open-label RCT in which 1078 patients with a recent hospital admission for AHF, high NT-proBNP level at screening (>2500 pg/mL), and >10% decrease in NT-proBNP level between screening and randomization (with NT-proBNP >1500 pg/mL before discharge) were enrolled. Within 2 days before the anticipated discharge date, participants were randomized to a HIC strategy, consisting of early uptitration of oral HF medications and close follow-up with multiple early ambulatory visits, or usual care.

Patients in the HIC group had follow-up visits at 1, 2, 3, and 6 weeks after randomization. In this group, oral doses of beta-blocker, ACEi/ARB/ARNI, and MRA were rapidly uptitrated to full optimal doses at week 2, guided by NT-proBNP, serum potassium, and eGFR levels, and systolic blood pressure. Usual care was provided according to local practice.

At baseline, the following 8 non-cardiac comorbidities were reported: anemia, diabetes, renal dysfunction, severe liver disease, COPD/asthma, stroke/TIA, psychiatric/neurological disorders, and malignancies.

Outcomes

The primary endpoint was a composite outcome of first HF rehospitalization or all-cause mortality at 180 days. Secondary endpoints included all-cause mortality at 180 days and the change in quality of life as assessed by the EuroQol-5D (EQ-5D) visual analogue scale (VAS) score from baseline to 90 days. To evaluate safety, the incidence of adverse events and serious adverse events at 90 days was assessed.

Main results

Non-cardiac comorbidities and oral HF therapy uptitration

• The prevalence of 0, 1, 2 and ≥3 non-cardiac comorbidities was 24.3%, 39.8%, 24.5% and 11.4%, respectively. The most common non-cardiac comorbidity was renal dysfunction (52.0%), followed by diabetes (29.1%), anemia (27.2%), and history of stroke/TIA (9.2%).
• In the HIC group, similar proportions of patients achieved full doses of guideline-directed medical therapies (GDMTs) at 90 and 180 days, irrespective of their number of non-cardiac comorbidities.

Clinical outcomes

• In the HIC group, the primary endpoint occurred in 10.0%, 16.6%, 13.6% and 26.2% of the patients with 0, 1, 2 and ≥3 non-cardiac comorbidities, respectively, compared with 19.1%, 25.4%, 23.3% and 26.2% of those in the usual-care group (P for interaction in unadjusted model=0.80; P for interaction in adjusted model=0.95).
• There was also no significant interaction between the treatment effect and non-cardiac comorbidity number for 180-day all-cause mortality (P for interaction in adjusted model=0.79) and change in EQ-5D VAS score (P for interaction in adjusted model=0.99 ).
• In addition, the treatment benefit of HIC over usual care on the primary endpoint did not differ significantly by any individual comorbidity (all P for interaction>0.05).

Safety

• The most common adverse events were cardiac related (99 in the HIC group vs. 96 in the usual-care group). There was no significant interaction between the incidence of any adverse event and non-cardiac comorbidity number (P for interaction=0.28).
• The incidence rate of serious adverse events increased with the number of non-cardiac comorbidities, but with no significant interaction by non-cardiac comorbidity number (P for interaction=0.11).

Conclusion

References

Find this article online at Eur J Heart Fail.