Dataset Information

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

ABSTRACT:

Aims

Patients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo.

Methods and results

Among 18 924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment, the primary outcome of major adverse cardiovascular events (MACE) was compared in patients with or without a history of HF. The pre-specified secondary outcome of hospitalization for HF was also analysed. Overall, 2815 (14.9%) patients had a history of HF. Alirocumab reduced low-density lipoprotein cholesterol and lipoprotein(a) similarly in patients with or without HF. Overall, alirocumab reduced MACE compared with placebo [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.78-0.93; P = 0.0001]. This effect was observed among patients without a history of HF (HR: 0.78; 95% CI: 0.70-0.86; P < 0.0001), but not in those with a history of HF (HR: 1.17; 95% CI: 0.97-1.40; P = 0.10) (Pinteraction = 0.0001). Alirocumab did not reduce hospitalization for HF, overall or in patients with or without prior HF.

Conclusion

Alirocumab reduced MACE in patients without a history of HF but not in patients with a history of HF. Alirocumab did not reduce hospitalizations for HF in either group. Patients with a history of HF are a high-risk group that does not appear to benefit from PCSK9 inhibition after ACS.

SUBMITTER: White HD

PROVIDER: S-EPMC9020985 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

White Harvey D HD Schwartz Gregory G GG Szarek Michael M Bhatt Deepak L DL Bittner Vera A VA Chiang Chern-En CE Diaz Rafael R Goodman Shaun G SG Jukema Johan Wouter JW Loy Megan M Pagidipati Neha N Pordy Robert R Ristić Arsen D AD Zeiher Andreas M AM Wojdyla Daniel M DM Steg Philippe Gabriel PG

European heart journal 20220401 16

<h4>Aims</h4>Patients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo.<h4>Methods and results</h4>Among 18 924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment, the primary outcome of major adverse cardio ...[more]

PMID: 34922353

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Project description:BackgroundGiven high on-treatment mortality in heart failure (HF), identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and are emerging as biomarkers of disease, but less is known about their role in the acute setting, particularly in the setting of HF.MethodsWe examined the ex-RNA profiles of 296 acute coronary syndrome (ACS) survivors enrolled in the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education Cohort. We measured 374 ex-RNAs selected a priori, based on previous findings from a large population study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes (left ventricular [LV] ejection fraction, LV mass, LV end-diastolic volume, left atrial [LA] dimension, and LA volume index) then tested relations of these ex-RNAs with prevalent HF (N=31, 10.5%). We performed further bioinformatics analysis of microRNA (miRNAs) predicted targets' genes ontology categories and molecular pathways.ResultsWe identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF. Of these 44 exRNAs, miR-29-3p, miR-584-5p, and miR-1247-5p were also associated with prevalent HF. The three microRNAs were implicated in the regulation p53 and transforming growth factor-β signaling pathways and predicted to be involved in cardiac fibrosis and cell death; miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.ConclusionsAmong ACS survivors, we observed that miR-29-3p, miR-584-5p, and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for patientsmiR-29c-3p, miR-584-5p, and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.

Project description:AimsLittle is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization.Methods and resultsWe analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all-cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age < 80 years [adjusted odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.41-2.20, P < 0.001], men (adjusted OR = 1.28, 95% CI = 1.03-1.59, P = 0.02), diabetes (adjusted OR = 1.27, 95% CI = 1.02-1.60, P = 0.04), no atrial fibrillation or flutter (adjusted OR = 1.45, 95% CI = 1.17-1.82, P < 0.001), no prior device implantation (adjusted OR = 1.81, 95% CI = 1.13-2.91, P = 0.01), current smoking (adjusted OR = 1.40, 95% CI = 1.05-1.87, P = 0.02), no cognitive dysfunction (adjusted OR = 1.90, 95% CI = 1.34-2.69, P < 0.001), ambulatory status (adjusted OR = 2.89, 95% CI = 2.03-4.10, P < 0.001), HF with reduced ejection fraction (adjusted OR = 1.55, 95% CI = 1.24-1.93, P < 0.001), estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (adjusted OR = 1.93, 95% CI = 1.45-2.58, P < 0.001), no anaemia (adjusted OR = 1.27, 95% CI = 1.02-1.59, P = 0.04), and no prescription of β-blockers prior to admission (adjusted OR = 1.32, 95% CI = 1.03-1.68, P = 0.03). Patients who underwent coronary angiography had a lower risk of the primary outcome [adjusted hazard ratio (HR) = 0.70, 95% CI = 0.58-0.85, P < 0.001]. Among the patients who underwent coronary angiography, those with coronary stenosis (38.9%) did not have lower risk of the primary outcome measure than those without coronary stenosis (adjusted HR = 0.93, 95% CI = 0.65-1.32, P = 0.68). Among the patients with coronary stenosis, those with coronary revascularization (54.3%) did not have higher risk of the primary outcome measure than those without coronary revascularization (adjusted HR = 1.36, 95% CI = 0.84-2.21, P = 0.22).ConclusionsIn patients with acute HF, patients who underwent coronary angiography had a lower risk of clinical outcomes and were significantly different from those who did not undergo coronary angiography.

Dataset Information

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

Aims

Methods and results

Conclusion

Publications

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

Similar Datasets

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