Patient Characteristics, Clinical Outcomes, and Effect of Dapagliflozin in Relation to Duration of Heart Failure

Abstract

Background : The impact of heart failure (HF) duration on outcomes and treatment effect is largely unknown. We aim to compare baseline patient characteristics, outcomes and the efficacy and safety of dapagliflozin, in relation to time from diagnosis of HF in DAPA-HF. Methods : HF duration was categorized as ≥2 to ≤12 months, >1-2 years, >2-5 years and >5 years. Outcomes were adjusted for prognostic variables and analyzed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect was examined within each duration category and by duration threshold. Results : The number of patients in each category was: 1098 (≥2 to ≤12 months), 686 (>1-2 years), 1105 (>2-5 years) and 1855 (>5 years). Longer-duration HF patients were older and more comorbid with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for ≥2 to ≤12 months, 10.6 (8.7-12.9) >1-2 years, 15.5 (13.6-17.7) >2-5 years and 15.9 (14.5-17.6) for >5 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration and on threshold analysis. The hazard ratio for the primary outcome ≥2 to ≤12 months was 0.86 (0.63-1.18), >1-2 years 0.95 (0.64-1.42), >2-5 years 0.74 (0.57-0.96) and >5 years 0.64 (0.53-0.78), P-interaction=0.26. The absolute benefit was greatest in longest duration HF, with a number needed-to-treat of 18 for HF >5 years, compared with 28 for ≥2 to ≤12 months. Conclusions : Longer-duration HF patients were older, had more comorbidity and symptoms, and higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Registration : ClinicalTrials.gov; Unique identifier: NCT03036124

‘Time is prognosis’ in heart failure: time‐to‐treatment initiation as a modifiable risk factor

“…Interestingly, patients with a longer HF duration in SHIFT 59 and DAPA‐HF 24 had a similar relative risk reduction with ivabradine and dapagliflozin, respectively, and a greater absolute risk reduction, compared with those with more recently diagnosed HF. 24 , 59 For these reasons, HF therapy should be optimized as soon as possible, as those with a longer HF duration might benefit at least as well. This might apply not only to drug therapies but also to implantable cardioverter defibrillator as even in later stages the risk of sudden cardiac death remained the same with shorter or longer duration of HF.…”

“…Also, this figure shows which trial did or did not meet its primary endpoints. Data taken from several studies 8,9,21–23,24,25–27 …”

Dapagliflozin — a key pawn on the new guidelines chessboard

“…However, the relative benefit of dapagliflozin was consistent across the whole spectrum of HF duration. The hazard ratio for the primary outcome of HF duration of ≥ 2 to ≤ 12 months was 0.86 (0.63-1.18), > 1 to 2 years 0.95 (0.64-1.42), > 2 to 5 years 0.74 (0.57-0.96), and > 5 years 0.64 (0.53-0.78); p for interaction = 0.26 [17]. The use of dapagliflozin also resulted in improvement of symptoms of HF, as measured on the Kansas City Cardiomyopathy Questionnaire (KCCQ) -a validated, self-administered instrument that quantifies HF-related symptoms, function, and quality of life [18].…”

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient

“…In particular, their effectiveness according with disease duration, as well as the effect in HF outpatients and the combined effectiveness of SGLT2i with other drugs administered in HF patients. In this regard, Yeoh et al analyzed the effect of Dapagliflozin in HF patients of DAPA-HF trial, according to HF duration [95]. In fact, HF is a progressive disease and patients with long-standing HF are older, with more comorbidities and more prone to develop the advanced disease with related complications.…”