Rapid GDMT uptitration improves all dimensions of QoL after hospitalization for acute HF

02/07/2024

Analysis of STRONG-HF showed rapid uptitration of guideline-directed medical therapy (GDMT) improved all dimensions of quality of life (QoL) at 90 days compared with usual care in patients hospitalized for acute HF, regardless of their baseline health status.

This summary is based on the publication of Čelutkienė J, Čerlinskaitė-Bajorė K, Cotter G, et al. - Impact of Rapid Up-Titration of Guideline-Directed Medical Therapies on Quality of Life: Insights From the STRONG-HF Trial. Circ Heart Fail. 2024 Apr;17(4):e011221. doi: 10.1161/CIRCHEARTFAILURE.123.011221

Introduction and methods

Background

When asked what should be the goal of treatment, patients with HF frequently prefer a better quality of life (QoL) over longevity [1-5]. Results from the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) trial showed that early (2–6 weeks after discharge) and rapid uptitration of guideline-directed medical therapy (GDMT), combined with close follow-up, improved not only prognosis but also QoL in patients hospitalized for acute HF (AHF), compared with usual care [6].

Aim of the study

In an analysis of the STRONG-HF trial, the authors assessed the baseline level and changes in total QoL and its components, as well as the association of QoL with clinical outcomes, in patients with AHF receiving high-intensity care (HIC) or usual care.

Methods

The STRONG-HF trial was an international, multicenter, open-label, parallel-group RCT in which 1078 patients admitted to the hospital for AHF were randomized ≤2 days before the anticipated discharge to a HIC strategy or usual care. The HIC strategy comprised uptitration of oral HF medications (RAASi (ACEi/ARB/ARNI), beta-blocker, and MRA) to half optimal doses at randomization and to full doses at 2 weeks. QoL was measured with the EuroQol (EQ) 5D-5L questionnaire. Patients ranked their state of health on 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) on a 5-point ordinal scale ranging from no problems to extreme problems. Baseline QoL assessments were available for 1072 patients.

Outcomes

The study’s primary endpoint was a composite outcome of first HF readmission or all-cause mortality at 180 days. Secondary endpoints were the change in patient’s self-rated overall health as assessed with the EQ-5D visual analog scale (EQ-VAS) score from baseline to 90 days, all-cause mortality at 180 days, and a composite outcome of first HF readmission or all-cause mortality at 90 days. Safety analysis included the incidence of treatment-emergent adverse events.

Main results

Change in QoL at 90 days

  • The improvement in the EQ-VAS score from baseline to 90 days was larger in patients assigned to the HIC strategy than those receiving usual care (adjusted mean difference: 3.5 points; 95%CI: 1.7–5.2; P<0.001).
  • At baseline, patients mostly suffered from limitations in mobility and usual activities according to the EQ-5D-5L assessment. At 90 days, patients in the HIC strategy group experienced fewer problems in all 5 EQ-5D-5L domains than those in the usual-care group (all P<0.05).
  • Subgroup analysis demonstrated no statistically significant heterogeneity in the benefits of the HIC strategy across patient subgroups stratified by age, LVEF, baseline systolic blood pressure, baseline NT-proBNP level, or history of atrial fibrillation or flutter.
  • In multivariable-adjusted analysis, the strongest independent predictors of improvement in the EQ-VAS score were younger age (P<0.001), no HF hospitalization in the previous year (P<0.001), lower NYHA class before hospitalization (P<0.001), and randomization to the HIC strategy (mean difference for HIC vs. usual are: 4.2; 95%CI: 2.5–5.8; P<0.001).

Association of QoL with clinical outcomes

  • The treatment benefit of the HIC strategy on the primary endpoint did not vary significantly by EQ-VAS score tertile at baseline (P for interaction=0.58), nor when the baseline EQ-VAS score was analyzed as a continuous variable (P for interaction=0.87).

Relation between QoL and GDMT doses

  • In the HIC group, the mean percentage of optimal doses of GDMT (i.e., combination of all 3 medication classes) at 90 and 180 days did not depend on baseline EQ-VAS score tertile: The mean difference between the middle tertile (EQ-VAS score: 51–65 points) and lowest tertile (EQ-VAS score: ≤50 points) was 0.59 (95%CI: –2.73 to 3.93), whereas the mean difference between the highest tertile (EQ-VAS score: >65 points) and lowest tertile was –1.32 (95%CI: –4.67 to 2.04).

Safety

  • The frequencies of any adverse event, cardiac failure events, sudden deaths, and serious adverse events were higher in patients in the lower tertiles of the baseline EQ-VAS score (all P for interaction<0.05).
  • However, there was no significant interaction between QoL across baseline EQ-VAS score tertiles and treatment group for the incidence of adverse events or serious adverse events (all P for interaction>0.05).

Conclusion

This analysis of the STRONG-HF trial showed that the HIC strategy comprising early and rapid uptitration of GDMT and close follow-up improved all dimensions of QoL at 90 days in patients hospitalized for AHF compared with usual care, regardless of their self-assessed health status at baseline. Other strong independent predictors of QoL improvement were younger age, no HF hospitalization in the previous year, and lower NYHA class before hospitalization.

Baseline QoL was not associated with the treatment benefit of the HIC strategy on the primary endpoint of HF readmission or all-cause mortality at 180 days. Furthermore, the likelihood of patients assigned to the HIC strategy achieving optimal GDMT doses did not depend on baseline QoL.

Find this article online at Circ Heart Fail.

References

  1. Hooper J, Hartshorne-Evans N, Cunnington C, Ahmed FZ. Iron deficiency: the invisible comorbidity in HF: prioritising QoL as a target for treatment. Br J Cardiol. 2021;28:S15–S18
  2. Garcia-Olmos L, Batlle M, Aguilar R, Porro C, Carmona M, Alberquilla A, Sánchez-Gómez LM, Monge E, López-Rodríguez AB, Benito L, et al. Disability and quality of life in heart failure patients: a cross-sectional study. Fam Pract. 2019;36:693–698. doi: 10.1093/fampra/cmz017
  3. Kraai IH, Vermeulen KM, Luttik ML, Hoekstra T, Jaarsma T, Hillege HL. Preferences of heart failure patients in daily clinical practice: quality of life or longevity? Eur J Heart Fail. 2013;15:1113–1121. doi: 10.1093/eurjhf/hft071
  4. Lewis EF, Johnson PA, Johnson W, Collins C, Griffin L, Stevenson LW. Preferences for quality of life or survival expressed by patients with heart failure. J Heart Lung Transplant. 2001;20:1016–1024. doi: 10.1016/s1053-2498(01)00298-4
  5. Zannad F, Alikhaani J, Alikhaani S, Butler J, Gordon J, Jensen K, Khatib R, Mantovani L, Martinez R, Moore WF, et al. Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives. Eur J Heart Fail. 2023;25:478–487. doi: 10.1002/ejhf.2828
  6. Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022;400:1938–1952. doi: 10.1016/S0140-6736(22)02076-1

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