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Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.

ABSTRACT: Heart failure is a highly prevalent cardiovascular complication among patients receiving long-term hemodialysis, but the benefits of carvedilol, bisoprolol, and metoprolol controlled release/extended release on the outcomes of these patients remain unclear. In this study, we address the use of these 3 β-blockers and their associations with mortality. Long-term hemodialysis patients, aged ≥35 years, with new-onset heart failure and receiving various medications were identified through the use of 1999-2010 data from the Taiwan National Health Insurance Research Database. From the total of 4435 heart failure patients, we selected 1700 new users of the 3 β-blockers (study group) and 1700 nonusers (control group), by using matched cohorts according to their propensity scores, and then compared the 5-year all-cause mortality rates by using Cox proportional hazard regressions and time-dependent covariate adjustment. During 3944 person-years of follow-up, 666 (39.2%) deaths occurred within the study group, compared with 918 (54%) deaths during 2893 person-years of follow-up in the control group. The 5-year mortality rate for the study (control) group was 54.5% (70.3%); P<0.001. Adjusted hazard regression analyses revealed that the therapeutic effects of β-blockers remained significant for all-cause mortality (hazard ratio 0.80, 95% CI 0.72 to 0.90). Subgroup analyses revealed that patients in the study group receiving β-blockers plus renin-angiotensin system antagonists exhibited the lowest mortality rate, while the highest mortality rate was found among patients in the control group receiving neither β-blockers nor renin-angiotensin system antagonists. This study demonstrates that the 3 β-blockers were associated with improved survival in long-term hemodialysis patients with heart failure.

SUBMITTER: Tang CH

PROVIDER: S-EPMC4859376 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.

Tang Chao-Hsiun CH Wang Chia-Chen CC Chen Tso-Hsiao TH Hong Chuang-Ye CY Sue Yuh-Mou YM

Journal of the American Heart Association 20160106 1

<h4>Background</h4>Heart failure is a highly prevalent cardiovascular complication among patients receiving long-term hemodialysis, but the benefits of carvedilol, bisoprolol, and metoprolol controlled release/extended release on the outcomes of these patients remain unclear. In this study, we address the use of these 3 β-blockers and their associations with mortality.<h4>Methods and results</h4>Long-term hemodialysis patients, aged ≥35 years, with new-onset heart failure and receiving various m ...[more]

PMID: 26738790

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Project description:BackgroundCarvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population.Study designA retrospective cohort study using a new-user design.Setting & participantsMedicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012.PredictorCarvedilol versus metoprolol initiation.OutcomesAll-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period.MeasurementsSurvival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses.Results27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for β-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11).LimitationsResidual confounding may exist.ConclusionsRelative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.

Project description:The study investigates the prognostic role of treatment with carvedilol as compared to metoprolol in patients with ventricular tachyarrhythmias. A large retrospective registry was used including consecutive patients on beta-blocker (BB) treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with carvedilol were compared to patients with metoprolol. The primary prognostic outcome was all-cause mortality at three years. Secondary endpoints comprised a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies) and cardiac rehospitalization. Kaplan-Meier survival curves, multivariable Cox regression analyses, and propensity score matching were applied for statistics. There were 1098 patients included, 80% treated with metoprolol and 20% with carvedilol. Patients with carvedilol were older, more often presenting with VT (78% vs. 62%; p = 0.001) and with more advanced stages of heart failure. Treatment with carvedilol was associated with comparable all-cause mortality compared to metoprolol (20% vs. 16%, log rank p = 0.234; HR = 1.229; 95% CI 0.874-1.728; p = 0.235). However, secondary endpoints (i.e., composite arrhythmic endpoint: 32% vs. 17%; p = 0.001 and cardiac rehospitalization: 25% vs. 14%; p = 0.001) were more frequently observed in patients with carvedilol, which was still evident after multivariable adjustment. After propensity score matching (n = 194 patients with carvedilol and metoprolol), no further differences regarding the distribution of baseline characteristics were observed. Within the propensity-score-matched cohort, higher rates of the composite arrhythmic endpoint were still observed in patients treated with carvedilol, whereas the risk of cardiac rehospitalization was not affected by the type of beta-blocker treatment. In conclusion, carvedilol and metoprolol are associated with comparable all-cause mortality in patients with ventricular tachyarrhythmias, whereas the risk of the composite arrhythmic endpoint was increased in patients with carvedilol therapy.

Project description:Hypertension treatment commonly requires multiple agents to achieve target blood pressure (BP). β-blockers and angiotensin-converting enzyme inhibitors (ACEIs) are commonly co-prescribed in clinical practice although few data are available that test their additivity on BP lowering. The efficacy and safety of once-daily extended-release carvedilol (carvedilol CR) combined with the ACEI lisinopril in a double-blind, randomized, factorial design study were studied. Patients (N=656) with stage 1 or 2 hypertension were randomized evenly to 1 of 15 groups for 6 weeks: carvedilol CR monotherapy 20 mg, 40 mg, or 80 mg/d; lisinopril monotherapy 10 mg, 20 mg, or 40 mg/d; or 1 of 9 combinations of carvedilol CR plus lisinopril initiated simultaneously. Primary efficacy measures (assessed by ambulatory BP monitoring [ABPM]) were change from baseline in 24-hour mean diastolic BP (DBP) and in trough (20-24 hours) DBP. Continuous efficacy variables were assessed using analysis of covariance. Whether any combination dose was superior to its monotherapy components was assessed using the Hung AVE procedure. Despite the presence of additional BP lowering observed with most of the combinations compared with their monotherapy components, the Hung AVE test was not significant for either primary efficacy measures. Post hoc analyses of the high-dose combination groups (carvedilol CR/lisinopril regimens of 80/10 mg, 80/20 mg, 80/40 mg, 20/40 mg, and 40/40 mg) showed a significant treatment difference compared with both carvedilol CR 80 mg and lisinopril 40 mg for 24-hour mean DBP but not for trough DBP. With the exception of dizziness, individual adverse events did not increase with ascending doses or combinations. The superiority of initiating combination treatment with carvedilol CR and lisinopril compared with the monotherapy components was not demonstrated with the ABPM measurements. Nonetheless, the post hoc assessment combining all high-dose groups did produce significant 24-hour mean BP reduction when compared with the high-dose monotherapy groups. The tolerability profile of initiating combination therapy was generally comparable to the initiation of treatment with monotherapy.

Project description:BackgroundThis analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).MethodsThe RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0-2 months, 3-5 months, 6-11 months, 12 months, or 13-18 months) with and without inverse probability weights adjusting for differences in baseline characteristics.ResultsOf 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0-2 months BUP-XR [n = 116]: 38.8%; 3-5 months BUP-XR [n = 61]: 41.0%; 6-11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results.ConclusionsParticipants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.

Dataset Information

Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.

Publications

Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.

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