FARXIGA (Page 10 of 13)

14.3 Heart Failure with Reduced Ejection Fraction

Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF, NCT03036124) was an international, multicenter, randomized, double-blind, placebo-controlled study in patients with heart failure (New York Heart Association [NYHA] functional class II-IV) with reduced ejection fraction (left ventricular ejection fraction [LVEF] 40% or less) to determine whether FARXIGA reduces the risk of cardiovascular death and hospitalization for heart failure.

Of 4744 patients, 2373 were randomized to FARXIGA 10 mg and 2371 to placebo and were followed for a median of 18 months. The mean age of the study population was 66 years, 77% were male and 70% were White, 5% Black or African-American, and 24% Asian.

At baseline, 68% patients were classified as NYHA class II, 32% class III, and 1% class IV; median LVEF was 32%. History of type 2 diabetes mellitus was present in 42%, and an additional 3% had type 2 diabetes mellitus based on a HbA1c ≥6.5% at both enrollment and randomization.

At baseline, 94% of patients were treated with ACEi, ARB or angiotensin receptor-neprilysin inhibitor (ARNI, including sacubitril/valsartan 11%), 96% with beta-blocker, 71% with mineralocorticoid receptor antagonist (MRA), 93% with diuretic, and 26% had an implantable device.

FARXIGA reduced the incidence of the primary composite endpoint of CV death, hospitalization for heart failure or urgent heart failure visit (HR 0.74 [95% CI 0.65, 0.85]; p<0.0001). All three components of the primary composite endpoint individually contributed to the treatment effect. The FARXIGA and placebo event curves separated early and continued to diverge over the study period (Table 15, Figures 6A, 6B and 6C).

Table 15: Treatment Effect for the Primary Composite Endpoint *, its Components * and All-Cause Mortality in the DAPA-HF Study
Patients with events (event rate)
Efficacy Variable (time to first occurrence) FARXIGA 10 mgN=2373 PlaceboN=2371 Hazard ratio(95% CI) p-value
*
Full analysis set.
Two-sided p-values.

Composite of Hospitalization for Heart Failure, CV Death or Urgent Heart Failure Visit

386 (11.6)

502 (15.6)

0.74 (0.65, 0.85)

<0.0001

Composite of CV Death or Hospitalization for Heart Failure

382 (11.4)

495 (15.3)

0.75 (0.65, 0.85)

<0.0001

Components of the composite endpoints

CV Death

227 (6.5)

273 (7.9)

0.82 (0.69, 0.98)

Hospitalization for Heart Failure or Urgent Heart Failure Visit

237 (7.1)

326 (10.1)

0.70 (0.59, 0.83)

Hospitalization for Heart Failure

231 (6.9)

318 (9.8)

0.70 (0.59, 0.83)

Urgent Heart Failure Visit

10 (0.3)

23 (0.7)

0.43 (0.20, 0.90)

All-Cause Mortality

276 (7.9)

329 (9.5)

0.83 (0.71, 0.97)

N=Number of patients, CI=Confidence interval, CV=Cardiovascular.

NOTE: Time to first event was analyzed in a Cox proportional hazards model. The number of first events for the single components are the actual number of first events for each component and does not add up to the number of events in the composite endpoint. Event rates are presented as the number of subjects with event per 100 patient years of follow-up.

Figure 6: Kaplan-Meier Curves for the Primary Composite Endpoint (A), Cardiovascular Death (B), and Heart Failure Hospitalization (C) (DAPA-HF Study)

Figure 6A: Time to the First Occurrence of the Composite of Cardiovascular Death, Hospitalization for Heart Failure or Urgent Heart Failure Visit

Figure 6A
(click image for full-size original)

NOTE: An urgent heart failure visit was defined as an urgent, unplanned, assessment by a physician, e.g., in an Emergency Department, and requiring treatment for worsening heart failure (other than just an increase in oral diuretics).

Patients at risk is the number of patients at risk at the beginning of the period.

HR=Hazard ratio, CI=Confidence interval.

Figure 6B: Time to the First Occurrence of Cardiovascular Death

Figure 6B
(click image for full-size original)

Patients at risk is the number of patients at risk at the beginning of the period.

HR=Hazard ratio, CI=Confidence interval.

Figure 6C: Time to the First Occurrence of Heart Failure Hospitalization

Figure 6C
(click image for full-size original)

Patients at risk is the number of patients at risk at the beginning of the period.

HR=Hazard ratio, CI=Confidence interval.

FARXIGA reduced the total number of hospitalizations for heart failure (first and recurrent) events and CV death, with 567 and 742 total events in the FARXIGA-treated vs placebo group (Rate Ratio 0.75 [95% CI 0.65, 0.88]; p=0.0002).

The results of the primary composite endpoint were consistent across the subgroups examined, including heart failure patients with and without type 2 diabetes mellitus (Figure 7).

Figure 7: Treatment Effects for Primary Composite Endpoint (Cardiovascular Death and Heart Failure Events) Subgroup Analysis (DAPA-HF Study)

Figure 7
(click image for full-size original)

a Hazard ratio estimates are not presented for subgroups with less than 15 events in total, both arms combined.

n/N# Number of subjects with event/number of subjects in the subgroup.

NT-proBNP = N-terminal pro b-type natriuretic peptide, HF = Heart failure, MRA = mineralocorticoid receptor antagonist,

ECG = electrocardiogram, eGFR = estimated glomerular filtration rate.

Note: The figure above presents effects in various subgroups, all of which are baseline characteristics. The 95% confidence limits that are shown do not take into account the number of comparisons made and may not reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be over-interpreted.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.