Project description:IntroductionIn patients with conduction abnormalities or left ventricle (LV) dysfunction the use of β-blockers for post cardiac surgery rhythm control is difficult and controversial, with a paucity of information about other drugs such ivabradine used postoperatively. The objective of this study was to compare the efficacy and safety of ivabradine versus metoprolol used perioperatively in cardiac surgery patients with conduction abnormalities or LV systolic dysfunction.MethodsThis was an open-label, randomized clinical trial enrolling 527 patients with conduction abnormalities or LV systolic dysfunction undergoing coronary artery bypass grafting or valvular replacement, randomized to take ivabradine or metoprolol, or metoprolol plus ivabradine. The primary endpoints were the composites of 30-day mortality, in-hospital atrial fibrillation (AF), in-hospital three-degree atrioventricular block and need for pacing, in-hospital worsening heart failure (HF; safety endpoints), duration of hospital stay and immobilization and the above endpoint plus in-hospital bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint).ResultsHeart rate reduction and prevention of postoperative AF or tachyarrhythmia with combined therapy was more effective than with metoprolol or ivabradine alone during the immediate postoperative management of cardiac surgery patients. In the Ivabradine group, the frequency of early postoperative pacing and HF worsening was smaller than in the Metoprolol group and in combined therapy group. The frequency of primary combined endpoint was lower in the combined Ivabradine + Metoprolol group compared with the monotherapy groups.ConclusionConsidering efficacy and safety, the cardiac rhythm reduction after open heart surgery in patients with conduction abnormalities or LV dysfunction with ivabradine plus metoprolol emerged as the best treatment in this trial.
Project description:Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.
Project description:Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood. We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9-1.8) and in 2.1% (95% CI 1.6-2.8), AHF in 1.6% (95% CI 1.2-2.2) and in 4.2% (95% CI 3.4-5.1), spontaneous MI in 0.5% (95% CI 0.3-0.9) and in 1.6% (95% CI 1.2-2.2), and PMI in 13.2% (95% CI 11.9-14.7) and in 14.8% (95% CI 13.4-16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104-163), indicating a vulnerable period of 3-5 months. One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery. https://www.clinicaltrials.gov. Unique identifier: NCT02573532.
Project description:Introductionβ-Blockers are a heterogenous class of drugs that are no longer recommended for initial antihypertension monotherapy due to unfavorable long-term cardiovascular events observed with non-vasodilatory β-blockers. However, the comparative cardiovascular event risk between the vasodilatory β1-selective antagonist/β3 agonist nebivolol and non-vasodilatory β1-blockers, atenolol and metoprolol, is unknown.MethodsIncident nebivolol, atenolol, or metoprolol monotherapy users with hypertension were identified using US claims data (2007-2014). The first β-blocker claim on/after 1/1/2008 defined the index drug/date. Hypertensive patients without pre-index cardiovascular history were followed until index drug discontinuation (> 90 day supply gap), use of other β-blockers, or end of continuous plan enrollment. Patients were pair-wise propensity score-matched using logistic regression, adjusted for baseline demographics, Charlson Comorbidity Index score, comorbid chronic pulmonary disease, rheumatic disease, renal disease, and diabetes, and use of other antihypertensive drugs during baseline. Time to first hospital claim for a cardiovascular event was assessed via Cox proportional hazards regression, adjusted for the variables above.ResultsInclusion criteria were met by 81,402 patients (n = 27,134 in each matched treatment cohort), with no between-cohort differences in baseline characteristics, comorbid conditions, or average follow-up duration. Atenolol and metoprolol cohorts had greater risk of hospitalization for a composite event (myocardial infarction, angina, congestive heart failure, stroke) than nebivolol users (adjusted hazard ratios [95% confidence interval] atenolol: 1.68 [1.29, 2.17]; metoprolol: 2.05 [1.59, 2.63]; P < 0.001, both). Risks of most individual cardiovascular events were also lower with nebivolol, including myocardial infarction and angina versus atenolol, and myocardial infarction, congestive heart failure, and angina versus metoprolol (P < 0.05, all).ConclusionsNebivolol was associated with significantly lower risk of hospitalization due to composite cardiovascular events than atenolol or metoprolol in this large retrospective cohort study of monotherapy with three different β1-selective blockers in hypertensive patients.FundingAllergan plc, Madison, NJ, USA.
Project description:BackgroundPerioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records.MethodsData from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta‑analysis.ResultsAfter 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta‑analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk).ConclusionsA nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.
Project description:BackgroundThere is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT).MethodsIn this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment.ResultsIn total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI.ConclusionsThis trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).
Project description:ObjectiveTo test whether atenolol (a long acting beta blocker) and metoprolol (a short acting beta blocker) are associated with equivalent reductions in risk for elderly patients undergoing elective surgery.DesignPopulation based, retrospective cohort analysis.SettingAcute care hospitals in Ontario, Canada, over one decade.ParticipantsConsecutive patients older than 65 who were admitted for elective surgery, without symptomatic coronary disease.Main outcome measureDeath or myocardial infarction.Results37,151 patients were receiving atenolol or metoprolol before surgery, of which the most common operations were orthopaedic or abdominal procedures. As expected, the two groups were similar in demographic characteristics, medical therapy, and type of surgery. 1038 patients experienced a myocardial infarction or died, a rate that was significantly lower for patients receiving atenolol than for those receiving metoprolol (2.5% v 3.2%, P < 0.001). The decreased risk with atenolol persisted after adjustment for measured demographic, medical, and surgical factors; extended to comparisons of other long acting and short acting beta blockers; was accentuated in analyses that focused on patients with the clearest evidence of beta blocker treatment; and reflected the immediate postoperative interval.ConclusionsPatients receiving metoprolol do not have as low a perioperative cardiac risk as patients receiving atenolol, in accord with possible acute withdrawal after missed doses.