1.
Redefining β-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.
Karwath, A, Bunting, KV, Gill, SK, Tica, O, Pendleton, S, Aziz, F, Barsky, AD, Chernbumroong, S, Duan, J, Mobley, AR, et al
Lancet (London, England). 2021;(10309):1427-1435
Abstract
BACKGROUND Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation. METHODS Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012). FINDINGS 15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from β blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67-1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of β blockers versus placebo (OR 0·92, 0·77-1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with β blockers (OR 0·57, 0·35-0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p<0·0001 vs random), and cluster membership was externally validated across the nine independent trials. INTERPRETATION An artificial intelligence-based clustering approach was able to distinguish prognostic response from β blockers in patients with heart failure and reduced LVEF. This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where β blockers did reduce mortality. FUNDING Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.
2.
Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis.
Stritzke, A, Kabra, N, Kaur, S, Robertson, HL, Lodha, A
Journal of perinatology : official journal of the California Perinatal Association. 2019;(12):1584-1594
Abstract
OBJECTIVE To systematically assess the efficacy of oral beta blockage treatment in primary (before established) and secondary (in threshold stages) prevention of severe retinopathy of prematurity (ROP) in premature infants born ≤32 weeks gestational age. STUDY DESIGN Following the PRISMA guidelines, published literature was systematically assessed up to April 27, 2018. Trials and observational studies, in which beta blockage was used to prevent severe ROP (defined as stage ≥3, or requiring treatment) were included. Meta-analyses including random effects models were conducted to determine the overall effect of oral beta blockage on prevention of ROP. RESULTS Six studies (five clinical trials and one observational study) including 461 infants met inclusion criteria using propranolol. The pooled relative risk (RR) of severe ROP in the primary and secondary prophylaxis groups were 0.65 (95% CI 0.43-0.98, NNT = 7) and 0.48 (95% CI 0.35-0.65, NNT = 6) in RCTs, respectively. The RR of severe ROP in one observational study was 0.21 (95% CI 0.08-0.55) with a NNT of 3. There were low heterogeneity and publication bias. Side effects occurred in 8.4% of participants on propranolol. CONCLUSIONS Systematic assessment of studies showed that prophylactic oral propranolol appeared to be effective in preventing severe ROP in premature infants ≤32 weeks gestational age. Additional well powered, multinational, randomized control trials reporting on long-term outcomes are needed.
3.
Preoperative Use of Oral Beta-Adrenergic Blocking Agents and the Incidence of New-Onset Atrial Fibrillation After Cardiac Surgery. A Systematic Review and Meta-Analysis.
Thein, PM, White, K, Banker, K, Lunny, C, Mirzaee, S, Nasis, A
Heart, lung & circulation. 2018;(3):310-321
Abstract
BACKGROUND Current epidemiological data suggests that postoperative atrial fibrillation or atrial flutter (POAF) causes significant morbidity and mortality after cardiac surgery. The literature for prophylactic management of POAF is limited, resulting in the lack of clear guidelines on management recommendations. AIM: To examine the efficacy of prophylactic rate control agents in reducing the incidence of new-onset POAF in patients undergoing elective cardiac surgery. METHODS Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Medline were systematically searched for blinded randomised controlled studies (RCT) evaluating adults with no history of atrial fibrillation randomised to a pharmacological agent (either beta blocker, calcium channel blocker or digoxin), compared to placebo. Utilising Cochrane guidance, three reviewers screened, extracted and the quality of the evidence was assessed. We used a random effects meta-analysis to compare a rate-control agent with placebo. RESULTS Five RCTs (688 subjects, mean age 61±8.9, 69% male) were included. Beta blocker administration prior to elective cardiac surgery significantly reduced the incidence of POAF (OR 0.43, 95%Cl [0.30-0.61], I2=0%) without significant impact on ischaemic stroke (OR 0.49, 95%Cl [0.10-2.44], I2=0%), non-fatal myocardial infarction (OR 0.76, 95%Cl [0.08-7.44], I2=0%), overall mortality (OR 0.83, 95%Cl [0.19-3.66], I2=0%), or length of stay (mean -0.96days 95%Cl [-1.49 to -0.42], I2=0%). An increased rate of bradycardic episodes was observed (OR 3.53, 95%Cl [1.22-10.23], I2=0%). CONCLUSIONS This review suggests that selective administration of prophylactic oral beta blockers prior to elective cardiac surgery is safe and may reduce the incidence of POAF.