Comparative Effectiveness of Beta-Adrenergic Antagonists (Atenolol, Metoprolol Tartrate, Carvedilol) on the Risk of Rehospitalization in Adults With Heart Failure

doi:10.1016/j.amjcard.2007.03.084

The American Journal of Cardiology

Volume 100, Issue 4, 15 August 2007, Pages 690-696

https://doi.org/10.1016/j.amjcard.2007.03.084 Get rights and content

Placebo-controlled randomized trials have demonstrated the efficacy of selected β blockers on outcomes in chronic heart failure (HF), but the relative effectiveness of different β blockers in usual clinical care is poorly understood. We compared 12-month risk of rehospitalization for HF associated with receipt of different β blockers in 7,883 adults hospitalized for HF within 2 large health plans between January 1, 2001 and December 31, 2002. Beta-blocker use was ascertained from electronic pharmacy databases and readmissions within 12 months were identified from hospital discharge databases. Extended Cox regression was used to examine the association between receipt of different β blockers and risk of readmission for HF after adjustment for potential confounders. During follow-up, there were 3,234 person-years of exposure to β blockers (39.3% atenolol, 42.0% metoprolol tartrate, 12.3% carvedilol, and 6.4% other). Crude 12-month rates of readmissions for HF were high overall (42.6 per 100 person-years). After adjustment for potential confounders, cumulative exposure to each β blocker, and propensity to receive carvedilol compared with atenolol, adjusted risks of readmission were not significantly different for metoprolol tartrate (adjusted hazard ratio 0.95, 95% confidence interval 0.85 to 1.05) or for carvedilol (adjusted hazard ratio 0.92, 95% confidence interval 0.74 to 1.14). In conclusion, in a contemporary cohort of high-risk patients hospitalized with HF, we found that adjusted risks of rehospitalization for HF within 12 months were not significantly different in patients receiving atenolol, shorter-acting metoprolol tartrate, or carvedilol.

Section snippets

Study sample

Patients were identified from Kaiser Permanente of Northern California (Oakland, California), a large integrated health care delivery system providing care for >3.2 million patients, and Harvard Pilgrim Health Care (Boston, Massachusetts), a not-for-profit network-based health plan providing care to >900,000 members. The study was approved by institutional review boards at collaborating institutions and waiver of informed consent was obtained given the nature of the study.

We identified adults

Baseline characteristics in overall cohort and in those receiving versus not receiving beta blockers

During 2001 and 2002, we identified 7,883 eligible survivors of a hospitalization for HF. There was a high prevalence of previous cardiovascular disease and documented vascular risk factors, chronic lung disease, and atrial fibrillation/flutter in cohort members.

Within 30 days before admission, 40% of patients received a β blocker, with the most commonly used being atenolol and metoprolol tartrate, and relatively few patients receiving metoprolol succinate, carvedilol, or other β blockers (

Discussion

Within a large cohort of older adults recently hospitalized with HF, we examined the comparative effectiveness of different β blockers in treated patients. We found that 68% of the cohort received a β blocker at discharge and/or during the first 12 months after discharge, with the most frequently used β blockers in our population being atenolol, shorter-acting metoprolol tartrate, and carvedilol, respectively. In patients with HF receiving β blockers, there were notable differences in

Acknowledgment

We thank Jim Livingston, MBA, Inna Dashevsky, and Ning Hernandez for their expert technical assistance on this study.

References (8)

P.A. Poole-Wilson et al.
Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial
Lancet
(2003)
G.C. Fonarow et al.
Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF)
Am Heart J
(2007)
W.Y. Lee et al.
Gender and risk of adverse outcomes in heart failure
Am J Cardiol
(2004)
S.A. Hunt et al.
ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society
Circulation
(2005)

There are more references available in the full text version of this article.

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Although all patients were included in all analyses, parameter estimates for those with missing proteinuria data were not shown, as it is not clear how best to interpret outcomes in those patients. While we relied on electronic medical records for key data elements, the KPNC data sources used are much more comprehensive than administrative databases and allow for thorough characterization of individual patients.41,43–53 Although use of urine protein-to-creatinine ratio (or albumin-to-creatinine ratio) would be a more accurate quantitative measure for proteinuria than dipstick assessment, these measurements are performed much less often than dipstick measurements are.21
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The protective effect of BBs on mortality or hospitalization has been confirmed in real-life in CHF patients, regardless of whether ejection fraction (EF) was preserved (EF ≥50%: Hazard Ratio, HR 0.68, 95%CI 0.52; 0.94) or reduced (EF <50%, HR 0.52, 95%CI 0.41; 0.69) [66]., Evidence suggests that there is no substantial difference in term of all-cause mortality and/or hospitalization among the individual BBs [67–69]; moreover, there is no difference between BBs listed in guidelines of CHF (carvedilol, metoprolol, and bisoprolol), and the non-listed ones (atenolol, propranolol, and timolol) [70]. One head-to-head study compared metoprolol and carvedilol.
The management of chronic cardiovascular diseases has evolved greatly in the last decades. Over the last thirty years, the management of acute coronary syndrome has improved, leading to an important lowering of the mortality in the acute phase of the event. Consequently, the optimal management of the secondary prevention of acute coronary syndrome has greatly evolved. Moreover, the increased number of pharmacological alternatives for patients affected by chronic heart failure and by non-valvular atrial fibrillation reserves a number of challenges for their correct management. Moreover, these diseases are without any reasonable doubt the largest contributor to global mortality in the present and will continue to be it in the future.
The aim of this study was to provide the most updated information of the real-life drug use and their effectiveness. This review was performed to assess the potential knowledge gaps in the treatments of these diseases and to indicate potential perspective of pharmaco-epidemiological research in this area.
Data Sources for Heart Failure Comparative Effectiveness Research
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Among 2929 patients with documented left ventricular systolic dysfunction, no significant adjusted differences were observed among the β-blocker uses. Adjusted hazards of rehospitalization for heart failure within 12 months did not differ significantly among treatment groups.73 The major challenge in linking different data sources is the availability of identifying information in each dataset.
Analysis of cost effectiveness of the use of metoprolol succinate in the treatment of hypertension and heart failure in Colombia
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realizar una evaluación de costo-efectividad del uso de metoprolol succinato frente a metoprolol tartrato y carvedilol en el tratamiento de pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, desde la perspectiva del tercero pagador.
el estudio se desarrolló mediante un modelo de Markov simulando la historia natural de la enfermedad para un horizonte temporal de cinco años, para lo cual se tomaron 100 pacientes con edad de 45 años. Se evaluaron como desenlaces tanto las hospitalizaciones como las muertes evitadas. Los datos de probabilidades se obtuvieron de estudios clínicos y los costos de bases de datos de instituciones y opinión de expertos, expresados en pesos colombianos de 2009. Se aplicó una tasa de descuento del 3%.
el costo del brazo tratado con metoprolol succinato fue el menor, con 299 millones de pesos frente a 364 millones y 346 millones de pesos para carvedilol y metoprolol tartrato, respectivamente. El menor número de hospitalizaciones se presentó con metoprolol succinato, y fue de 24 ingresos en el horizonte de tiempo. En el brazo con carvedilol fue donde ocurrieron menos muertes. Los índices mostraron que el metoprolol succinato fue dominante frente a los otros beta-bloqueadores en las hospitalizaciones evitadas y en las muertes en comparación con metoprolol tartrato.
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to conduct an assessment of cost-effectiveness of the use of metoprolol succinate versus metoprolol tartrate and carvedilol in the treatment of patients with congestive heart failure and hypertension in Colombia, from the third party payer's perspective.
the study was conducted using a Markov model simulating the natural history of the disease for a time horizon of five years, taking 100 patients aged 45 years. Both hospitalizations and deaths avoided were evaluated as outcomes. The probability data were obtained from clinical studies and the costs of institutions databases and expert opinion, expressed in Colombian pesos of 2009. We applied a discount rate of 3%.
the cost of metoprolol succinate treated arm was the lowest, with 299 million pesos compared to 364 million and 346 million pesos for carvedilol and metoprolol tartrate, respectively. The lower number of hospitalizations occurred with metoprolol succinate, and corresponded with 24 admissions at the time horizon. In the carvedilol arm occurred fewer deaths. The indices showed that metoprolol succinate was dominant over the other beta-blockers in avoiding hospitalizations and deaths in comparison with metoprolol tartrate.
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However, there was no difference in the decrease seen in cardiovascular mortality or mortality from pump failure between carvedilol and other β blockers. In an observational study by Go et al24 in a subset of patients with left ventricular systolic dysfunction, no statistically significant difference in readmission rates was found with carvedilol compared with atenolol (adjusted HR 1.18, 95% CI 0.70 to 2.01). In the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) study,25 a secondary analysis demonstrated no statistically significant difference in all-cause mortality at 90 days between carvedilol and nonevidence-based β blockers in patients with an ejection fraction <40% who were recently discharged from the hospital (propensity-adjusted HR 0.70, 95% CI 0.41 to 1.22).
Beta blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are evidence-based medications for chronic heart failure, but little is known about the persistent use and clinical effectiveness of these medications. We evaluated the longer-term use of β blockers and ACEIs/ARBs in patients with left ventricular systolic dysfunction and coronary artery disease. Patients with an ejection fraction <40% and coronary artery disease who had a cardiac catheterization from April 1994 through December 2005 were identified. Long-term patterns of β-blocker and ACEI/ARB use were categorized as persistent, new, previous, or no use based on information from routine follow-up surveys. Characteristics among medication-use groups were explored, and survival associated with persistent use was determined. Of 3,187 patients identified for the β-blocker analysis, 1,339 (42.0%) had persistent use. Conditional on surviving for ≥2 follow-up surveys, the adjusted risk of death was statistically significantly lower with persistent use versus no use (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.65 to 0.82) and new use versus no use (HR 0.81, 95% CI 0.68 to 0.97). Adjusted risk of death was not statistically significantly different between persistent or new use of an evidence-based β blocker and persistent use of a nonevidence-based β blocker (HR 0.96, 95% CI 0.78 to 1.17). Of 3,166 patients identified for the ACEI/ARB analysis, 1,347 (42.5%) had persistent use. There was no statistically significant association between adjusted mortality and persistent use (HR 0.93, 95% CI 0.81 to 1.05), new use (HR 0.86, 95% CI 0.71 to 1.03), or previous use (HR 0.88, 95% CI 0.73 to 1.07) compared with no ACEI/ARB use. In conclusion, persistent and new use of β blockers was associated with survival, but evidence-based β blockers did not appear superior to nonevidence-based β blockers. We were unable to demonstrate a statistically significant association between persistent ACEI/ARB use and survival.
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2009, Journal of the American College of Cardiology
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Our study strengthens the findings of previous studies by including important clinical characteristics, such as LVEF, and prospective data on eligibility for treatment, including contraindications and intolerance. Go et al. (24) analyzed medical records from 2 health care systems to assess the comparative effectiveness of beta-blockers on the risk of rehospitalization for heart failure. After adjustment for risks of admission and propensity to receive beta-blockers, they did not find significant differences in rehospitalization within 12 months for patients on atenolol, metoprolol tartrate, carvedilol, or other beta-blockers.
We sought to examine associations between initiation of beta-blocker therapy and outcomes among elderly patients hospitalized for heart failure.
Beta-blockers are guideline-recommended therapy for heart failure, but their clinical effectiveness is not well understood, especially in elderly patients.
We merged Medicare claims data with OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) records to examine long-term outcomes of eligible patients newly initiated on beta-blocker therapy. We used inverse probability–weighted Cox proportional hazards models to determine the relationships among treatment and mortality, rehospitalization, and a combined mortality–rehospitalization end point.
Observed 1-year mortality was 33%, and all-cause rehospitalization was 64%. Among 7,154 patients hospitalized with heart failure and eligible for beta-blockers, 3,421 (49%) were newly initiated on beta-blocker therapy. Among patients with left ventricular systolic dysfunction (LVSD) (n = 3,001), beta-blockers were associated with adjusted hazard ratios of 0.77 (95% confidence interval [CI]: 0.68 to 0.87) for mortality, 0.89 (95% CI: 0.80 to 0.99) for rehospitalization, and 0.87 (95% CI: 0.79 to 0.96) for mortality–rehospitalization. Among patients with preserved systolic function (n = 4,153), beta-blockers were associated with adjusted hazard ratios of 0.94 (95% CI: 0.84 to 1.07) for mortality, 0.98 (95% CI: 0.90 to 1.06) for rehospitalization, and 0.98 (95% CI: 0.91 to 1.06) for mortality–rehospitalization.
In elderly patients hospitalized with heart failure and LVSD, incident beta-blocker use was clinically effective and independently associated with lower risks of death and rehospitalization. Patients with preserved systolic function had poor outcomes, and beta-blockers did not significantly influence the mortality and rehospitalization risks for these patients.

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: This research was conducted by Kaiser Permanente of Northern California and Harvard Pilgrim Health Care under contract to the Agency for Healthcare Research and Quality (Contract HHSA29020050033I), Rockville, Maryland. The authors are responsible for its content. No statement may be construed as the official position of the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

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Heart failureComparative Effectiveness of Beta-Adrenergic Antagonists (Atenolol, Metoprolol Tartrate, Carvedilol) on the Risk of Rehospitalization in Adults With Heart Failure

Section snippets

Study sample

Baseline characteristics in overall cohort and in those receiving versus not receiving beta blockers

Discussion

Acknowledgment

Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial

Lancet

Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF)

Am Heart J

Gender and risk of adverse outcomes in heart failure

Am J Cardiol

Circulation

Heart failure
Comparative Effectiveness of Beta-Adrenergic Antagonists (Atenolol, Metoprolol Tartrate, Carvedilol) on the Risk of Rehospitalization in Adults With Heart Failure