TY - JOUR
T1 - Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction
T2 - A Post Hoc Analysis of the DAPA-HF Trial
AU - Butt, Jawad H
AU - Dewan, Pooja
AU - Merkely, Béla
AU - Belohlávek, Jan
AU - Drożdż, Jarosław
AU - Kitakaze, Masafumi
AU - Inzucchi, Silvio E
AU - Kosiborod, Mikhail N
AU - Martinez, Felipe A
AU - Tereshchenko, Sergey
AU - Ponikowski, Piotr
AU - Bengtsson, Olof
AU - Lindholm, Daniel
AU - Langkilde, Anna Maria
AU - Schou, Morten
AU - Sjöstrand, Mikaela
AU - Solomon, Scott D
AU - Sabatine, Marc S
AU - Chiang, Chern-En
AU - Docherty, Kieran F
AU - Jhund, Pardeep S
AU - Køber, Lars
AU - McMurray, John J V
PY - 2022/6
Y1 - 2022/6
N2 - BACKGROUND: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments.OBJECTIVE: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure).DESIGN: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124).SETTING: 410 sites in 20 countries.PATIENTS: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide.INTERVENTION: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.MEASUREMENTS: The primary outcome was worsening HF or cardiovascular death.RESULTS: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class.LIMITATION: Enrollment criteria precluded the inclusion of very high-risk patients.CONCLUSION: Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients.PRIMARY FUNDING SOURCE: AstraZeneca.
AB - BACKGROUND: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments.OBJECTIVE: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure).DESIGN: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124).SETTING: 410 sites in 20 countries.PATIENTS: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide.INTERVENTION: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.MEASUREMENTS: The primary outcome was worsening HF or cardiovascular death.RESULTS: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class.LIMITATION: Enrollment criteria precluded the inclusion of very high-risk patients.CONCLUSION: Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients.PRIMARY FUNDING SOURCE: AstraZeneca.
KW - Benzhydryl Compounds
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Frailty/complications
KW - Glucosides
KW - Heart Failure/drug therapy
KW - Humans
KW - Stroke Volume
KW - Ventricular Dysfunction, Left
KW - Ventricular Function, Left
UR - http://www.scopus.com/inward/record.url?scp=85132453939&partnerID=8YFLogxK
U2 - 10.7326/M21-4776
DO - 10.7326/M21-4776
M3 - Journal article
C2 - 35467935
SN - 0003-4819
VL - 175
SP - 820
EP - 830
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 6
ER -