Current decompensated HF or HF hospitalization Estimated glomerular filtration rate (eGFR) ≤30 ml/m/1.73m2.Unacceptable side effects associated with SGLT2i.All drug doses were individually tailored, and dosing of anti-hyperglycemics including insulin was titratable as seen fit by the prescribing physician. MRA (mineralocorticoid receptor antagonism) use was encouraged. ≥ 900pg/mL if patient had atrial fibrillation/flutter on baseline ECG.Īdditionally, all patients were required to receive standard heart-failure device therapy (ICD, CRT or both) and standard drug therapy (ACEi/ARB/ARNI + beta-blocker unless contraindicated or resulting in unacceptable side effects).≥ 400pg/mL if they were hospitalized for HF within the past 12 months OR.Patients were included if they met all of the following criteria: Primary outcome: Composite of worsening HF or CV death.Setting: 410 centers in 20 countries (14% North America).N=4,744 patients with HFrEF, EF ≤40%, and NYHA II-IV symptoms.
#DECLARE TRIAL DAPAGLIFLOZIN TRIAL#
Multicenter, double-blind, parallel-group, randomized, controlled trial.If HFpEF or HFmrEF, SGLT2i can be useful for lowering HF mortality and HF hospitalizations (COR 2a, LOE B-R).If symptomatic chronic HFrEF, SGLT2i recommended to reduce HF hospitalizations and CVD mortality, regardless of diabetes status (COR 1, LOE A).Of note, the related EMPEROR-Preserved (2021) trial and DELIVER (2022) confirmed benefit of SGLT2-inhibitors in HFmrEF and HFpEF.ĪCC/AHA/HFSA heart failure (2022, adapted) These findings were later confirmed in the EMPEROR-Reduced (2020) trial. Overall, the results of DAPA-HF confirm the benefit of SGLT-2 inhibition in patients with HFrEF and T2DM, and provide initial evidence of their efficacy in patients with HFrEF without T2DM. Adverse events were similar in both arms. Importantly, subgroup analyses demonstrated similar improvements in patients with and without T2DM. There was also a 2.3% absolute reduction in all-cause mortality. Results indicated that SGLT-2 inhibitor therapy resulted in a 4.9% absolute reduction in the primary outcome of CV death or worsening HF, defined as urgent evaluation or hospitalization for HF. DAPA-HF randomly assigned nearly 5,000 patients receiving standard medical care to dapagliflozin or placebo. The 2019 DAPA-HF trial was conducted to study whether the addition of the SGLT-2 inhibitor dapagliflozin could benefit patients with HFrEF, either with or without T2DM. Prior studies were not powered to examine this class of medications in the setting of HF with reduced ejection fraction (HFrEF). In the more recent DECLARE-TIMI 58 study, dapagliflozin did not show a statistically significant reduction in the primary outcome of major adverse CV events but did show a reduction in the composite of CV death or hospitalization for HF. Though the mechanisms of cardiovascular benefit remains unclear, it is likely to be driven by a reduction in HF death given that rates of MI were similar between treatment arms. EMPA-REG and CANVAS showed reductions in composite primary outcomes of CV mortality, nonfatal MI, or nonfatal stroke, as well as reductions in HF hospitalizations among patients with diabetes. Because of this, the development of three new sodium-glucose cotransporter 2 (SGLT-2) inhibitors for diabetic patients was accompanied by three cardiovascular outcomes trials ( CANVAS, EMPA-REG OUTCOME, and DECLARE-TIMI 58 ).
In 2008, the US Food and Drug Administration began requiring every new drug for diabetes to be tested in a cardiovascular outcomes trial. In individuals with heart failure with reduced ejection fraction (NYHA II-IV, LVEF ≤40%) with or without diabetes, does the addition of the SGLT-2 inhibitor dapagliflozin reduce rates of cardiovascular death or worsening heart failure?Īmong individuals with HFrEF (NYHA II-IV, LVEF ≤40%) with or without T2DM, the addition of the SGLT-2 inhibitor dapagliflozin decreased rates of CV death or worsening HF, as well as all-cause mortality.
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