Medical Therapy for Heart Failure With Reduced Ejection Fraction

Greene, Stephen J.; Butler, Javed; Albert, Nancy M.; DeVore, Adam D.; Sharma, Puneet; Duffy, Charles J.; Hill, C. Larry; McCague, Kevin; Mi, Xiaojuan; Patterson, J. Herbert; Spertus, John A.; Thomas, Laine; Williams, Fredonia B.; Hernandez, Adrian F.; Fonarow, Gregg C.

doi:10.1016/j.jacc.2018.04.070

Cited by 931 publications

(818 citation statements)

References 20 publications

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“…Consistent with this, the majority (58%) of patients enrolled in DAPA‐HF did not have known diabetes. The proportion with an existing diagnosis of diabetes (42%) was similar to that in contemporary registries but somewhat larger than in the comparator HFrEF trials . The patients randomized in DAPA‐HF were also broadly similar, in other respects, to those in the recent registries, although, as has been recognized previously, atrial fibrillation was less frequent in Asian patients .…”

Section: Discussionsupporting

confidence: 70%

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The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics

McMurray

DeMets

Inzucchi

et al. 2019

European J of Heart Fail

195

133

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Background The aims of this study were to: (i) report the baseline characteristics of patients enrolled in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial, (ii) compare DAPA‐HF patients to participants in contemporary heart failure (HF) registries and in other recent HF trials, and (iii) compare individuals with diabetes, pre‐diabetes and a normal glycated haemoglobin (HbA1c) in DAPA‐HF. Methods and results Adults with HF in New York Heart Association functional class ≥ II, a left ventricular ejection fraction ≤ 40%, an elevated N‐terminal pro‐B‐type natriuretic peptide concentration and receiving standard treatment were eligible for DAPA‐HF, which is comparing dapagliflozin 10 mg once daily to matching placebo. In patients without a history of diabetes, previously undiagnosed diabetes was defined as a confirmed HbA1c ≥ 6.5%. Among patients without known or undiagnosed diabetes, pre‐diabetes was defined as a HbA1c ≥ 5.7% The remainder of patients, with a HbA1c < 5.7%, were defined as normoglycaemic. Of the 4744 patients (mean age 66 years; 23% women) randomized, 42% had known diabetes and 3% undiagnosed diabetes. Of the remainder, 67% had pre‐diabetes and 33% normal HbA1c. Overall, DAPA‐HF patients were generally similar to those in recent registries and in relevant trials and had high levels of background therapy: 94% angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor, 96% beta‐blocker, and 71% mineralocorticoid receptor antagonist; 26% had a defibrillator. Patients with diabetes had worse HF status, more co‐morbidity, and greater renal impairment but received similar HF therapy. Patients with diabetes received non‐insulin hypoglycaemic therapy alone in 49%, insulin alone in 11%, both in 14%, and none in 26%. Conclusions Patients randomized in DAPA‐HF were similar to those in other contemporary HF with reduced ejection fraction (HFrEF) registries and trials. These patients were receiving recommended HFrEF therapy and those with diabetes were also treated with conventional glucose‐lowering therapy. Consequently, DAPA‐HF will test the incremental efficacy and safety of dapagliflozin in HFrEF patients with and without diabetes. Clinical Trial Registration: http://ClinicalTrials.gov Identifier NCT03036124

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Section: Discussionsupporting

confidence: 70%

“…Three recent registries encompassing Europe, Asia and the United States of America (USA) were used for comparison of patients in DAPA‐HF with the so‐called ‘real‐world’ cohorts …”

Section: Methodsmentioning

confidence: 99%

The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics

McMurray

DeMets

Inzucchi

et al. 2019

European J of Heart Fail

195

133

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“…The finding that 62% of the patients up‐titrated to 49/51 or 97/103 mg bid of sacubitril/valsartan are relevant when compared to registry data, showing only 43% of patients receiving more than 24/26 mg bid of sacubitril/valsartan in an outpatient setting . This gap between data from controlled trials and daily practice requires further study, and gives room for future improvement in HF therapy .…”

Section: Discussionmentioning

confidence: 96%

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

Wachter

Senni

Bělohlávek

et al. 2019

European J of Heart Fail

278

220

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Aims To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results TRANSITION was a randomised, multicentre, open‐label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre‐admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12‐h pre‐discharge or between Days 1–14 post‐discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up‐ or down‐titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day –1 and Day +1 in the pre‐discharge group and the post‐discharge group, respectively. Comparable proportions of patients in the pre‐ and post‐discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: http://ClinicalTrials.gov ID: NCT02661217

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“…Several large cohorts and trials have reported dose, including a Swedish multicentre cohort (n = 2093) 33 ; the BIOSTAT-CHF Optimal dosing of medication in acute heart failure study (n = 2100) 16 ; the ESC-HF, 6 CHAMP-HF, 8 CHECK-HF, 31 and PINNACLE (n = 1421) 34 registries; and the GUIDE-IT trial. 35 The proportions prescribed ≥50% and target dose for each class are ACE-I/ARB 40% to 76% for ≥50% and 14% to 44% target; beta-blockers 31% to 55% for ≥50% and 6% to 28% target; and MRA 49% to 98% for ≥50% and 31% to 77% target.…”

Section: Target Dosingmentioning

confidence: 99%

“…[1][2][3] Assessment of appropriate use requires patient-level knowledge of indications, contraindications, and tolerability. [6][7][8] Maximum tolerated doses were utilized in the landmark clinical trials, are recommended in guidelines, 1-3 and associated with improved outcomes but not excess discontinuation rates. [6][7][8] Maximum tolerated doses were utilized in the landmark clinical trials, are recommended in guidelines, 1-3 and associated with improved outcomes but not excess discontinuation rates.…”

Section: Introductionmentioning

confidence: 99%

Medical therapy doses at hospital discharge in patients with existing and de novo heart failure

et al. 2019

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Aims Uptitrating angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (ACE‐I/ARBs), beta‐blockers, and mineralocorticoid receptor antagonists (MRAs) to optimal doses in heart failure with reduced ejection fraction (HFrEF) is associated with improved outcomes and recommended in guidelines. Studies of ambulatory patients found that a minority are prescribed optimal doses. However, dose at hospital discharge has rarely been reported. This information may guide quality improvement initiatives during and following discharge. Methods and results We assessed 370 consecutive patients with HFrEF hospitalized at two centres in Vancouver, Canada. Of those without contraindications, 86.4%, 93.4%, and 44.7% were prescribed an ACE‐I/ARB/sacubitril–valsartan, beta‐blocker, or MRA, respectively. The proportion of eligible patients prescribed target dose was respectively 28.6%, 31.7%, and 4.1%. Forty‐two of 248 eligible patients (16.9%) were prescribed ≥50% of target dose, and only three patients received target dosing of all three medication classes. In multivariate regression models, cardiologist involvement in care was independently associated with increased dose and prescription of ≥50% of target dose for all medications, whereas a history of HF was only predictive for beta‐blockers. Conclusions In a single‐region experience of hospitalized HFrEF patients, a high proportion of eligible patients were discharged on ACE‐I/ARB or beta‐blocker. Less than half were prescribed MRAs, and few were prescribed ≥50% or target dosing of all medications. Further exploration into barriers to medication uptitration, and improvement in processes of care, is needed.

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Medical Therapy for Heart Failure With Reduced Ejection Fraction

Cited by 931 publications

References 20 publications

The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics

The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

Medical therapy doses at hospital discharge in patients with existing and de novo heart failure

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