Impact of Acute Beta-Blocker Therapy for Patients with Non–ST-Segment Elevation Myocardial Infarction

doi:10.1016/j.amjmed.2007.04.016

The American Journal of Medicine

Volume 120, Issue 8, August 2007, Pages 685-692

https://doi.org/10.1016/j.amjmed.2007.04.016 Get rights and content

Abstract

Purpose

Early use of beta-blockers is a quality indicator for the treatment of patients with non–ST-segment elevation myocardial infarction (NSTEMI), despite limited data from randomized clinical trials in this population. We sought to determine the impact of acute beta-blocker therapy on outcomes in patients with NSTEMI.

Subjects and Methods

We examined acute (<24 hours) beta-blocker use in 72,054 patients with NSTEMI from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) initiative at 509 US hospitals from 2001-2004. We analyzed patient and provider factors associated with beta-blocker use and the impact of beta-blocker therapy on unadjusted, risk-adjusted, and propensity matched outcomes in the overall sample and among selected high-risk subgroups.

Results

A total of 82.5% of patients without documented contraindications received acute beta-blocker therapy. Factors strongly associated with acute beta-blocker use included prior beta-blocker use, higher presenting systolic blood pressure, lower heart rate, lack of signs of heart failure, and cardiology care. Acute beta-blocker use was associated with lower in-hospital mortality (unadjusted 3.9% vs 6.9%, P <.001, adjusted odds ratio 0.66, 95% confidence interval 0.60-0.72), lower adjusted mortality among most of 6 subgroups determined by propensity to receive acute beta-blockers, and lower adjusted mortality in patients with and without signs of heart failure and in those <80 years and those ≥80 years old.

Conclusions

The majority of NSTEMI patients receive acute beta-blocker therapy. Certain patient subgroups remain undertreated. Because treatment with acute beta-blockers was associated with improved clinical outcomes in nearly all patient subgroups assessed, broader use in patients with NSTEMI appears warranted.

Section snippets

Methods

Patients meeting inclusion criteria for CRUSADE were identified locally by each site. Data collected included patient and hospital characteristics, use of acute medications (within 24 hours of presentation), medication contraindications, use and timing of invasive cardiac procedures, laboratory results, in-hospital outcomes, and discharge therapies and interventions.

Results

A total of 82.5% of patients received acute beta-blockers. Patients who received acute beta-blockers were younger, more commonly male, had prior myocardial infarction, were more commonly taking prior beta-blockers, were cared for by cardiologists at academic hospitals, and less commonly had prior or current heart failure (Table 1). The independent factors associated with acute beta-blocker use are listed in Table 2.

Patients treated with acute beta-blockers more commonly received other acute

Discussion

Our results show that more than 80% of eligible patients with non–ST-segment elevation myocardial infarction were treated with acute beta-blockers within 24 hours of hospital presentation. Patients who received acute beta-blockers were more likely to have been receiving beta-blockers prior to hospitalization, have stable hemodynamic features, and receive care on a cardiology inpatient service. Use of acute beta-blockers was associated with a lower adjusted risk of adverse outcomes across

References (19)

E. Braunwald et al.
ACC/AHA 2002 guideline update for the management of patients with unstable angina and non–ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina)
J Am Coll Cardiol
(2002)
S. Yusuf et al.
Beta blockade during and after myocardial infarction: an overview of the randomized trials
Prog Cardiovasc Dis
(1985)
J. McMurray et al.
Antiarrhythmic effect of carvedilol after acute myocardial infarction: results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial
J Am Coll Cardiol
(2005)
D.E. Forman et al.
Management of acute myocardial infarction in the very elderly
Am J Med
(1992)
Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction: ISIS-1
Lancet
(1986)
Metoprolol in acute myocardial infarction (MIAMI)A randomised placebo-controlled international trial
Eur Heart J
(1985)
R. Roberts et al.
Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarctionResults of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study
Circulation
(1991)
H.J. Dargie
Effect of carvedilol on outcome after myocardial infarction in patients with left ventricular dysfunction: the CAPRICORN randomised trial
Lancet
(2001)
Z.M. Chen et al.
Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial
Lancet
(2005)

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

Cited by (37)

Early beta-blocker therapy improves in-hospital mortality of patients with non-ST-segment elevation myocardial infarction – a meta-analysis
2023, International Journal of Cardiology
Although current guidelines endorse early beta-blocker therapy in stable patients with STEMI, there is no clear recommendation on the early use of these drugs in patients with NSTEMI.
Literature search was conducted by 3 independent researchers using PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS. Studies were eligible if (P) patients included were ≥ 18 years of age and had non-ST-segment elevation myocardial infarction (NSTEMI), (I) early (<24 h) treatment with intravenous or oral beta-blockers was compared to (C) no treatment with beta-blockers and data on (O) in-hospital mortality and/or in-hospital cardiogenic shock were depicted. Odds ratios and 95% confidence intervals were calculated using random effects models with the Mantel–Haenszel method. The Hartung-Knapp-Sidik-Jonkman method was used as estimator for τ².
977 records were screened for eligibility, which led to the inclusion of 4 retrospective, nonrandomized, observational cohort studies comprising a total of N = 184,951 patients. After pooling of the effect sizes, early therapy with beta-blockers resulted in a reduction of in-hospital mortality (OR 0.43 [0.36–0.51], p = 0.0022) despite no significant effect on the prevalence of cardiogenic shock (OR 0.36 [0.07–1.91], p = 0.1196).
Early treatment with beta-blockers was associated with an attenuation of in-hospital mortality despite no increase in cardiogenic shock. Thus, early therapy with these drugs could elicit beneficial effects on top of reperfusion therapy, similar to the effects seen in STEMI-patients. The low number of studies (k = 4) has to be considered when interpreting the findings of this analysis.
Comparison of early versus delayed oral β blockers in acute coronary syndromes and effect on outcomes
2016, American Journal of Cardiology
Citation Excerpt :
There are no randomized controlled trials of oral β blockers in the setting of ACS.12,20–22 Other observational studies describing the impact of the timing of β blocker administration on outcomes of patients with ACS are inconsistent for comparison with our data because these studies are pooled together, patients treated both orally and intravenously.23–25 Furthermore, we created a propensity score for the likelihood26–28 of undergoing in-hospital mortality using multiple logistic regressions with early versus delayed β blocker treatment as dependent variables and baseline clinical characteristics of the cohort as covariates including the index event.
The aim of this study was to determine if earlier administration of oral β blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous β blockers or remained free of any β blocker treatment during hospital stay, 23 as timing of oral β blocker administration was unknown, and 182 patients because they died before oral β blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral β blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early β blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early β blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score–matched analyses. In conclusion, in patients with ACSs, earlier administration of oral β blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.
Guía ESC 2015 sobre el tratamiento de los síndromes coronarios agudos en pacientes sin elevación persistente del segmento ST: Grupo de Trabajo de la Sociedad Europea de Cardiología (ESC) para el tratamiento de los síndromes coronarios agudos en pacientes sin elevación persistente del segmento ST
2015, Revista Espanola de Cardiologia
Los miembros del Comité de la ESC para la Elaboración de GPC y los revisores del documento representantes de las sociedades nacionales de cardiología aparecen listados en el apéndice.
Entidades de la ESC que han participado en el desarrollo de este documento:
Asociaciones: Asociación de Cuidados Cardiovasculares Agudos (ACCA), Asociación Europea para la Prevención y Rehabilitación Cardiovascular (EACPR), Asociación Europea de Imagen Cardiovascular (EACVI), Asociación Europea de Intervencionismo Coronario Percutáneo (EAPCI), Asociación de Insuficiencia Cardiaca (HFA).
Consejos: Consejo de Enfermería Cardiovascular y Profesiones Afines (CCNAP), Consejo de Práctica Cardiológica (CCP), Consejo de Cuidados Cardiovasculares Primarios (CCPC).
Grupos de Trabajo: Farmacoterapia Cardiovascular, Cirugía Cardiovascular, Fisiopatología y Microcirculación Coronaria, Trombosis.
El contenido de esta Guía de Práctica Clínica de la Sociedad Europea de Cardiología (ESC) se publica exclusivamente para uso personal y educativo. No se autoriza su uso comercial. No se autoriza la traducción o reproducción de ningún fragmento de esta guía sin la autorización escrita de la ESC. La autorización se solicitará por escrito a Oxford University Press, editorial de European Heart Journal y representante autorizado de la ESC para gestionar tales permisos.
Descargo de responsabilidad. Esta guía recoge la opinión de la ESC y se ha elaborado tras el estudio minucioso de los datos y la evidencia disponibles hasta la fecha. La ESC no es responsable en caso de que haya alguna contradicción, discrepancia o ambigüedad entre la guía de práctica clínica (GPC) de la ESC y cualquier otra recomendación oficial o GPC publicada por autoridades relevantes de la sanidad pública, particularmente en lo que se refiere al buen uso de la atención sanitaria y las estrategias terapéuticas. Se espera que los profesionales de la salud tengan en consideración esta GPC a la hora de tomar decisiones clínicas, así como al implementar estrategias médicas preventivas, diagnósticas o terapéuticas. No obstante, esta guía no anula la responsabilidad individual de cada profesional al tomar las decisiones oportunas relativas a cada paciente, de acuerdo con dicho paciente y, cuando fuera necesario, con su tutor o representante legal. Además, las GPC de la ESC no eximen al profesional médico de su obligación ética y profesional de consultar y considerar atentamente las recomendaciones y las GPC actualizadas emitidas por autoridades sanitarias competentes. Es también responsabilidad del profesional verificar la normativa y la legislación sobre fármacos y dispositivos médicos a la hora de prescribirlos.
Se puede consultar las declaraciones de conflicto de intereses de los expertos participantes en el desarrollo de esta guía en la página web de la ESC: www.escardio.org/guidelines
Pharmacological approach in the elderly with coronary artery disease
2015, Archives des Maladies du Coeur et des Vaisseaux - Pratique
National assessment of early β-blocker therapy in patients with acute myocardial infarction in China, 2001-2011: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Retrospective AMI Study
2015, American Heart Journal
Citation Excerpt :
We identified patient and health system factors that were associated with greater responsiveness to guideline recommendations, but gaps in quality of care with respect to early use of β-blocker therapy are pervasive and have not changed over the recent past. Patterns of underuse of β-blockers for AMI in China identified in this study have also been documented in other areas, including the United States,10–12 the Middle East,15 and Brazil.17 The benefits of β-blockers, when appropriately used in the early stages of AMI, are supported by substantial evidence1,2,4 and strong guideline recommendations.5–7,16,18–20
Since 2007, clinical practice guidelines have recommended β-blocker therapy early in the course of acute myocardial infarction (AMI) for patients who are not at high risk for complications. Our objective was to perform a national quality assessment of early β-blocker use during hospitalization for AMI over the past decade in China.
We conducted medical record review of a nationally representative sample of patients admitted to Chinese hospitals with AMI and studied those without absolute contraindications to β-blocker therapy in 2001, 2006, and 2011. We evaluated the use, type, and dose of β-blockers within the first 24 hours of admission over time and identified predictors of not using this treatment both in ideal candidates and in those with risk factors for cardiogenic shock.
Among 14,241 patients with AMI (representing 43,165 patients in 2001, 106,167 patients in 2006, and 221,874 patients in 2011 in China, respectively), 45.1% had no contraindications to early β-blocker therapy; 21.1% had risk factors for cardiogenic shock but no absolute contraindication. β-blocker use in ideal patients was 54.3% in 2001, 67.8% in 2006, and 61.8% in 2011 (P = .28 for trend). Predictors of nontreatment were older age, lower systolic blood pressure, lower heart rate, absence of chest discomfort, and admission to a nonteaching hospital. Use in patients with risk factors for cardiogenic shock was 42.6% in 2001, 59.5% in 2006, and 52.9% in 2011 (P = .31 for trend). Metoprolol was used most frequently (91.5%), but dosages were often below those recommended in guidelines.
The use of early β-blocker therapy for patients with AMI in China is suboptimal, with underuse in patients who could benefit and substantial use among those who might be harmed. Patterns of use have not changed over time, thus creating an important target of efforts to improve quality of care for AMI.
Adherence to ACC/AHA Performance Measures for Myocardial Infarction in Six Middle-Eastern Countries: Association with In-Hospital Mortality and Clinical Characteristics
2013, International Journal of Cardiology
Citation Excerpt :
The present study found large and statistically significant protective associations for beta-blocker use within 24 hours and reperfusion therapy among for whom these therapies were indicated, respectively. These results compare favorably with the CRUSADE study which also reported a strong and independent adjusted association between the use of beta blockers within 24 hours and lower in-hospital mortality (OR = 0.66; p < 0.001) [28]. Our inability to find statistical significance in the current analysis between aspirin use and lower in-hospital mortality may have occurred because there were only eight deaths in the group not receiving aspirin, resulting in low statistical power.
This study assesses adherence to performance measures for acute myocardial infarction (AMI) in six Middle-Eastern countries, and its association with in-hospital mortality. Few studies have previously assessed these performance measures in the Middle East.
This cohort study followed 5813 patients with suspected AMI upon admission to discharge. Proportions of eligible participants receiving the following performance measures were calculated: medications within 24 hours of admission (aspirin and beta-blocker) and on discharge (aspirin, beta-blockers, angiotensin converting enzyme inhibitors [ACEI], and lipid-lowering therapy), reperfusion therapy, and low-density lipoprotein (LDL) cholesterol measurement. A composite adherence score was calculated. Associations between performance measures and clinical characteristics were assessed using multivariate logistic regression.
Adherence was above 90% for aspirin, reperfusion, and lipid-lowering therapies; between 60% and 82% for beta-blockers, ACEI, statin therapy, time-to-balloon within 90 minutes, and LDL-cholesterol measurement; and 33% for time-to-needle within 30 minutes. After adjustment, factors associated with high composite performance score (> 85%) included Asian ethnicity (Odds Ratio, OR = 1.3; p = 0.01) and history of hyperlipidemia (OR = 1.4; p = 0.001). Factors associated with a lower score included atypical symptoms (OR = 0.6; p = 0.003) and high GRACE score (OR = 0.6; p < 0.001). Lower in-hospital mortality was associated with provision of reperfusion therapy (OR = 0.54, p = 0.047) and beta-blockers within 24 hours (OR = 0.33, p = 0.005).
Overall adherence was lowest among the highest-risk patients. Lower in-hospital mortality was independently associated with adherence to early performance measures, comprising observational evidence for their effectiveness in a Middle East cohort. These data provide a focus for regional quality improvement initiatives and research.

View all citing articles on Scopus

: CRUSADE is funded by the Schering-Plough Corporation. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership provides additional funding support. Millennium Pharmaceuticals, Inc. also funded this work.

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Clinical research studyImpact of Acute Beta-Blocker Therapy for Patients with Non–ST-Segment Elevation Myocardial Infarction

Abstract

Purpose

Subjects and Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

Prog Cardiovasc Dis

J Am Coll Cardiol

Am J Med

Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction: ISIS-1

Lancet

Metoprolol in acute myocardial infarction (MIAMI)A randomised placebo-controlled international trial

Eur Heart J

Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarctionResults of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study

Circulation

Effect of carvedilol on outcome after myocardial infarction in patients with left ventricular dysfunction: the CAPRICORN randomised trial

Lancet

Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial

Lancet

Clinical research study
Impact of Acute Beta-Blocker Therapy for Patients with Non–ST-Segment Elevation Myocardial Infarction