Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial.

Importance: Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies. Objective: To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial. Design, Setting, and Participants: The GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months. Interventions: Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo. Main Outcomes and Measures: The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability. Results: Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo. Conclusions and Relevance: In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited. Trial Registration: ClinicalTrials.gov Identifier: NCT02929329.

Prevalence and Correlates of Cost-Related Medication Nonadherence to Immunosuppressive Drugs After Heart Transplantation: The International Multicenter Cross-sectional Bright Study.

BACKGROUND: Cost-related medication nonadherence (CRMNA) refers to not taking medications as prescribed because of difficulties paying for them. OBJECTIVES: The aims of this study were (1) to assess the prevalence of CRMNA to immunosuppressants in heart transplant recipients internationally and (2) to determine multilevel correlates (patient, center, and healthcare system levels) of CRMNA. METHODS: Using data from the cross-sectional international BRIGHT study, applying multistaged sampling, CRMNA was assessed via 3 self-report items in 1365 patients from 36 heart transplant centers in 11 countries. Cost-related medication nonadherence was defined as any positive answer on any of the 3 items. Healthcare system-level (ie, insurance coverage, out-of-pocket expenditures) and patient-level (ie, intention, perceived financial burden, cost as a barrier, a health belief regarding medication benefits, cost-related self-efficacy, and demographic factors) CRMNA correlates were assessed. Correlates were examined using mixed logistic regression analysis. RESULTS: Across all study countries, CRMNA had an average prevalence of 2.6% (range, 0% [Switzerland/Brazil] to 9.8% [Australia]) and was positively related to being single (odds ratio, 2.29; 95% confidence interval, 1.17-4.47), perceived financial burden (odds ratio, 2.15; 95% confidence interval, 1.55-2.99), and cost as a barrier (odds ratio, 2.60; 95% confidence interval, 1.66-4.07). Four protective factors were identified: white ethnicity (odds ratio, 0.37; 95% confidence interval, 0.19-0.74), intention to adhere (odds ratio, 0.44; 95% confidence interval, 0.31-0.63), self-efficacy (odds ratio, 0.54; 95% confidence interval, 0.43-0.67), and belief about medication benefit (odds ratio, 0.70; 95% confidence interval, 0.57-0.87). Regarding variability, 81.3% was explained at the patient level; 13.8%, at the center level; and 4.8%, at the country level. CONCLUSION: In heart transplant recipients, the CRMNA prevalence varies across countries but is lower than in other chronically ill populations. Identified patient-level correlates are novel (ie, intention to adhere, cost-related barriers, and cost-related self-efficacy) and indicate patient-perceived medication cost burden.