Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction

Lewis, Gregory D.; Voors, Adriaan A.; Cohen‐Solal, Alain; Metra, Marco; Whellan, David J.; Böhm, Michael; Teerlink, John R.; Docherty, Kieran F.; Lopes, Renato D.; Divanji, Punag; Heitner, Stephen B.; Kupfer, Stuart; Malik, Fady I.; Meng, Lisa; Wohltman, Amy; Felker, G. Michael

doi:10.1001/jama.2022.11016

Cited by 33 publications

(29 citation statements)

References 34 publications

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“…[145][146][147][148][149][150] In Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure (METEORIC-HF) trial, omecamtiv mecarbil did not improve functional capacity in patients with HFrEF over 20 weeks. 151 This drug remains therefore indicated to improve patients' outcomes. 2 Danicamtiv is another selective myosin activator capable of improving LV and atrial contractility in experimental models and in a Phase 2a trial in patients with HFrEF.…”

Section: Sodium-glucose Co-transporter-2 Inhibitorsmentioning

confidence: 99%

“…New insights from the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in HF (GALACTIC‐HF) trial show the efficacy and safety of the selective cardiac myosin activator omecamtiv mecarbil in patients with severe systolic HF and with systolic blood pressure (BP) ≤100 mmHg 145–150 . In Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure (METEORIC‐HF) trial, omecamtiv mecarbil did not improve functional capacity in patients with HFrEF over 20 weeks 151 . This drug remains therefore indicated to improve patients' outcomes 2 .…”

Section: Treatment Of Heart Failure With Reduced Ejection Fractionmentioning

confidence: 99%

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Heart failure: an update from the last years and a look at the near future

et al. 2022

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In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

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Section: Sodium-glucose Co-transporter-2 Inhibitorsmentioning

confidence: 99%

Section: Treatment Of Heart Failure With Reduced Ejection Fractionmentioning

confidence: 99%

Heart failure: an update from the last years and a look at the near future

et al. 2022

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“…What’s more, omecamtiv also results in a small reduction in heart rate ( 241 ). Unfortunately, omecamtiv did not improve exercise capacity compared with placebo over a period of 20 weeks in patients with chronic HFrEF ( 242 ).…”

Section: Discussionmentioning

confidence: 99%

Diabetic cardiomyopathy: Clinical phenotype and practice

et al. 2022

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Diabetic cardiomyopathy (DCM) is a pathophysiological condition of cardiac structure and function changes in diabetic patients without coronary artery disease, hypertension, and other types of heart diseases. DCM is not uncommon in people with diabetes, which increases the risk of heart failure. However, the treatment is scarce, and the prognosis is poor. Since 1972, one clinical study after another on DCM has been conducted. However, the complex phenotype of DCM still has not been fully revealed. This dilemma hinders the pace of understanding the essence of DCM and makes it difficult to carry out penetrating clinical or basic research. This review summarizes the literature on DCM over the last 40 years and discusses the overall perspective of DCM, phase of progression, potential clinical indicators, diagnostic and screening criteria, and related randomized controlled trials to understand DCM better.

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“…One possibility is that participants in METEORIC-HF had less severe heart failure as compared with participants in GALACTIC-HF and, thus, were less likely to benefit from omecamtiv mecarbil as described previously. Although the median LVEF in both trials was 28%, the frequency of NYHA class II symptoms was 78.6% vs 53.2%, the median N-terminal pro–brain natriuretic peptide levels were 791 pg/mL (IQR, 422-1475) vs 1971 pg/mL (IQR, 961-4033), and the median Kansas City Cardiomyopathy Questionnaire score was 85.4 (IQR, 67.2-95.8) vs 68.8 (IQR, 49-87.5) in the respective trials . These data support a lower severity of illness among the METEORIC-HF participants compared with the GALACTIC-HF participants.…”

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confidence: 90%

“…4 The US Food and Drug Administration (FDA) has set a Prescription Drug User Fee Act target action date of November 30, 2022, for its standard review of omecamtiv mecarbil. 5 In this issue of JAMA, Lewis et al 6 report the results of the METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure) Trial and extend the evidence base regarding omecamtiv mecarbil in patients with chronic heart failure. In this double-blind, multicenter clinical trial, 276 participants with NYHA class II or III symptoms and an LVEF of 35% or less were randomized in a 2:1 ratio to omecamtiv mecarbil vs placebo and underwent cardiopulmonary stress testing at baseline and 20 weeks.…”

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confidence: 99%