Dapagliflozin in patients hospitalised with newly diagnosed heart failure: an analysis of the randomized DAPA ACT HF-TIMI 68 trial
P M Haller, S M Patel, M G Palazzolo, J Belohlavek, A S Desai, J Drozdz, S E Inzucchi, J J V Mcmurray, B Merkely, E O Meara, S Verma, S D Wiviott, M S Sabatine, D D BergAbstract
Background
Patients hospitalized for newly diagnosed heart failure (HF) are less well characterized than patients with worsening chronic HF. Clinical trials of novel HF therapies have traditionally excluded patients with newly diagnosed HF.
Methods
DAPA ACT HF-TIMI 68 was a randomized, double-blind, placebo-controlled trial of in-hospital initiation of dapagliflozin in patients hospitalized with a primary diagnosis of HF. In this prespecified subgroup analysis, we compared the clinical profiles and treatment effects of dapagliflozin vs. placebo in patients with newly diagnosed HF vs worsening chronic HF. The primary efficacy endpoint was the composite of cardiovascular death or first worsening HF (CVD/WHF) event through 2 months; death from any cause was a secondary endpoint. Key safety outcomes included symptomatic hypotension and worsening kidney function.
Results
Of 2401 randomized patients, 1074 (44.7%) had newly diagnosed HF during the index hospitalization. Compared to patients with worsening chronic HF, newly diagnosed patients were younger (median 64 [Q1-Q3, 54-74] vs. 71 [61-78] years) and had fewer comorbidities, including type 2 diabetes (26.4% vs. 42.8%), hypertension (68.1% vs. 86.4%), chronic kidney disease (34.3% vs. 54.2%), and atrial fibrillation (32.1% vs. 55.4%; all p<0.001). Although patients with newly diagnosed HF were less likely than patients with worsening chronic HF to be treated with neurohormonal antagonists (beta-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists) prior to admission (8.6% vs. 21.2% on all three, p<0.001), they were more likely to be treated with these agents by hospital discharge (48.6% vs. 39.6%, p<0.001) and through the remainder of follow-up. Compared to patients with worsening chronic HF, those with newly diagnosed HF had a lower rate of CVD/WHF (6.4% vs. 16.1%, p<0.001) and of death from any cause (1.8% vs. 5.3%, p<0.001) through 2 months. However, hazard ratios of dapagliflozin appeared similar in each group for both outcomes (Fig A). Adverse events occurred less frequently in patients with newly diagnosed HF as compared with worsening chronic HF; however, among newly diagnosed HF patients, there was an excess of symptomatic hypotension events in those randomized to dapagliflozin (3.1% vs. 1.2%, p=0.03) (Fig B).
Conclusion
DAPA ACT HF-TIMI 68 offers contemporary insights into patients hospitalized for newly diagnosed HF. The treatment effect of in-hospital initiation of dapagliflozin on clinical outcomes was generally consistent irrespective of HF chronicity.Fig. A: Efficacy endpointsFor image description, please refer to the figure legend and surrounding text.Fig. B: Safety endpointsFor image description, please refer to the figure legend and surrounding text.