Initiation Of Β-blockers Research Articles

Physician Perspectives on the Use of Beta Blockers in Heart Failure With Preserved Ejection Fraction

β-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for β-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding β-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for β-blocker initiation, agreement regarding initiation and/or continuation of β-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n=231). Among respondents, 68.2% reported initiating β-blockers in patients with HFpEF. The most common reason for initiating a β-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a β-blocker without an evidence-based indication. When a β-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a β-blocker when the physician felt that a β-blocker was unnecessary was the concern about interfering with another physicians' treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing β-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe β-blockers in these scenarios.

β-Blockade before Noncardiac Surgery: The Devil Is in the Details.

β-Blockade before Noncardiac Surgery: The Devil Is in the Details.

Does Slow and Steady Win the Race? Gaining Perspective on Preoperative β-Blocker Initiation

Complex Information for Anesthesiologists Presented Quickly and ClearlyPO, per os; POISE, PeriOperative ISchemic Evaluation.Infographic created by Holly B. Ende, Vanderbilt University Medical Center; James P. Rathmell, Brigham and Women’s Health Care/Harvard Medical School; and Jonathan P. Wanderer, Vanderbilt University Medical Center. Illustration by Annemarie Johnson, Vivo Visuals Studio. Address correspondence to Dr. Ende: holly.ende@vumc.org.

Anesthesiology

Perioperative β-blocker therapy has been associated with increased risk of stroke. In this issue of ANESTHESIOLOGY, McKenzie et al. test the hypothesis that there will be no association between preoperative β-blocker initiation within 60 days of surgery or chronic β-blockade and the risk of stroke in patients undergoing major abdominal surgery. In an accompanying editorial, Spence and Kheterpal address the questions surrounding β-blockers and highlight the critical role of large, well–executed randomized controlled trials in patient care. Cover illustration: A. Johnson, Vivo Visuals Studio.

Preoperative β-Blocker Therapy and Stroke or Major Adverse Cardiac Events in Major Abdominal Surgery: A Retrospective Cohort Study.

Perioperative β-blocker therapy has been associated with increased risk of stroke. However, the association between β-blocker initiation before the day of surgery and the risk of stroke is unknown. The authors hypothesized there would be no association between preoperative β-blocker initiation within 60 days of surgery or chronic β-blockade (more than 60 days) and the risk of stroke in patients undergoing major abdominal surgery. Data on elective major abdominal surgery were obtained from the IBM (USA) Truven Health MarketScan 2005 to 2015 Commercial and Medicare Supplemental Databases. Patients were stratified by β-blocker dispensing exposure: (1) β-blocker-naïve, (2) preoperative β-blocker initiation within 60 days of surgery, and (3) chronic β-blocker dispensing (more than 60 days). The authors compared in-hospital stroke and major adverse cardiac events between the different β-blocker therapy exposures. There were 204,981 patients who underwent major abdominal surgery. β-Blocker exposure was as follows: perioperative initiation within 60 days of surgery for 4,026 (2.0%) patients, chronic β-blocker therapy for 45,424 (22.2%) patients, and β-blocker-naïve for 155,531 (75.9%) patients. The unadjusted frequency of stroke for patients with β-blocker initiation (0.4%, 17 of 4,026) and chronic β-blocker therapy (0.4%, 171 of 45,424) was greater than in β-blocker-naïve patients (0.2%, 235 of 155,531; P < 0.001). After propensity score weighting, patients initiated on a β-blocker within 60 days of surgery (odds ratio, 0.90; 95% CI, 0.31 to 2.04; P = 0.757) or on chronic β-blocker therapy (odds ratio, 0.86; 95% CI, 0.65 to 1.15; P = 0.901) demonstrated similar stroke risk compared to β-blocker-naïve patients. Patients on chronic β-blocker therapy demonstrated lower adjusted risk of major adverse cardiac events compared to β-blocker-naïve patients (odds ratio, 0.81; 95% CI, 0.72 to 0.91; P = 0.007), despite higher unadjusted absolute event rate (2.6% [1,173 of 45,424] vs. 0.6% [872 of 155,531]). Among patients undergoing elective major abdominal surgery, the authors observed no association between preoperative β-blocker initiation within 60 days of surgery or chronic β-blocker therapy and stroke.

Dealing With Failure.

Dealing With Failure.

Analytical Approaches to Reduce Selection Bias in As-Treated Analyses with Missing In-Hospital Drug Information.

While much attention has focused on immeasurable time bias as a potential exposure misclassification bias, it may also result in potential selection bias in cohort studies using an as-treated (or per protocol) exposure definition in which patients are censored upon treatment discontinuation. We examined analytical approaches to minimise informative censoring due to the absence of in-hospital drug data using a case study of β-blocker use and mortality in heart failure. We conducted a cohort study using Korea's healthcare database, including inpatient and outpatient drug data. Using an as-treated exposure definition, patients were followed up until death, β-blocker discontinuation (in the exposed), β-blocker initiation (in the unexposed), or end of study period. In 'complete prescription' analysis using inpatient and outpatient drug data, we estimated hazard ratios (HR) and 95% confidence intervals (CI) using a Cox proportional hazard model. In outpatient drug-based analyses, we attempted to reduce the bias using stabilised inverse probability weighting (IPW) for treatment crossovers, hospitalisation, and all artificial censorings. An HR of 0.89 (95% CI 0.74-1.07) for β-blocker use versus non-use for all-cause mortality was found in 'complete prescription' analysis. Benefits were exaggerated when follow-up was assessed using outpatient drug data only (HR 0.71; 95% CI 0.57-0.89). Weighting by stabilised IPW for treatment crossovers and hospitalisation reduced the bias. When using an as-treated exposure definition, missing in-hospital drug data induced selection bias in our case study. Using IPW for censoring mitigated bias from the hospitalisation-induced censorings.

Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding. Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression. Eighty-seven patients (carvedilol/propranolol, n= 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P= .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P= .034). Cumulative incidences for rebleeding (Gray test, P= .027) and liver-related death (P= .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P= .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P= .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models. Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.

EP News: Pediatric and Congenital Electrophysiology

Peltenburg et al (Circulation 2022;145:333–344, PMID 34874747) investigated the association between risk for arrhythmic events and type of β-blocker in 329 symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT). RYR2 variant–carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and start of β-blocker therapy <18 years of age) from both the International CPVT Registry and the PACES Pediatric CPVT Registry were enrolled.

An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia.

Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT. From 2 international registries of patients with CPVT, RYR2 variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy <18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope. We included 329 patients (median age at diagnosis, 12 [interquartile range, 7-15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 [95% CI, 1.31-3.17]; and HR, 1.99 [95% CI, 1.20-3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44-4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47-7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08-4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30-5.55]). β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.

Modern Management of Nasal Hemangiomas

Current treatment approaches for infantile hemangiomas of the nose include observation, pharmacologic agents, surgery, and/or laser therapy. Because of the known functional, social, and cosmetic effect of nasal deformities, obtaining the best possible result is critical. Optimal timing, type, duration, and extent of therapy remain unclear. Results of a review of 86 patients (64 females and 22 males; mean age, 4.8 months [range, 2 days-23 years]) with infantile hemangiomas of the nose treated from January 1, 1999, to December 31, 2015, and a review of the literature are presented to gain insight into the preferred approach to the treatment of these lesions. Patients underwent single-modality and multimodality treatment with pulsed-dye laser (n = 73), oral corticosteroids (n = 11), intralesional corticosteroids (n = 2), propranolol hydrochloride (n = 30), and surgery (n = 50). The treatment decision algorithms and outcomes based on tumor phase and infantile hemangioma subtype are reviewed in detail. Nine articles met the criteria to be included in the literature review. Literature from the era before the approval of propranolol advocates for early use of oral or intralesional corticosteroids followed by surgery or pulsed-dye laser in cases of unacceptable outcomes. Literature from the era after the approval of propranolol supports early initiation of oral β-blockers until proliferation ceases or until additional intervention is necessary. Despite a lack of higher levels of evidence, there exists a general consensus between the literature and clinical experience advocating for early multimodality treatment to achieve the best result possible by the time the children reach certain sociodevelopmental milestones.

Factors associated with β-blocker initiation and discontinuation in a population-based cohort of seniors newly diagnosed with heart failure.

Purposeβ-Blockers (bisoprolol, carvedilol, and metoprolol) are the cornerstone of heart failure (HF) management. The incidence rate of β-blocker initiation and discontinuation and their associated factors among seniors with a first HF diagnosis were assessed.MethodsA population-based inception cohort study that included all individuals aged ≥65 years with a first HF diagnosis in Quebec was conducted. β-Blockers initiation among 91,131 patients who were not using β-blockers at the time of HF diagnosis and discontinuation among those who initiated a β-blocker after HF diagnosis were assessed. Stepwise Cox regression analyses were used to calculate hazard ratios (HR) and to identify factors associated with β-blocker initiation and discontinuation.ResultsAfter HF diagnosis, 32,989 (36.2%) individuals initiated a β-blocker. Of these, 15,408 (46.7%) discontinued their β-blocker during the follow-up. Individuals more likely to initiate a β-blocker were those diagnosed in a recent calendar year (2009: HR, 2.11; 95% confidence interval [CI], 2.00–2.23) and diagnosed by a cardiologist (HR, 1.38; 95% CI, 1.34–1.42). Individuals less likely to initiate were those aged ≥90 years (HR, 0.65; 95% CI, 0.61–0.68) and those with chronic obstructive pulmonary disease (HR, 0.66; 95% CI, 0.64–0.68). Individuals more likely to discontinue were those with more than nine medical consultations (HR, 1.14; 95% CI, 1.10–1.18) and those with dementia (HR, 1.13; 95% CI, 1.01–1.27). Individuals less likely to discontinue were those diagnosed in a recent calendar year (2009: HR 0.74; 95% CI, 0.65–0.82) and those exposed to another β-blocker before HF diagnosis (HR, 0.88; 95% CI, 0.85–0.91).ConclusionQuebec seniors seem to be underexposed to β-blocker following HF diagnosis. Among those who initiate β-blocker use, discontinuation is high. Better understanding of the underlying causes is needed to help target interventions to improve the management of HF.

Predictors of β-Blocker Initiation After Myocardial Infarction in Patients With Type 2 Diabetes

Background: Beta-blockers remain important for secondary prevention after myocardial infarction (MI). Despite clinical guideline recommendations, underutilization of this pharmacotherapy continues in patients with type 2 diabetes (T2DM) compared to the general post-MI population. Objective: This study aimed to (1) quantify the proportion of T2DM patients utilizing β-blocker therapy within 30 days of hospital discharge after MI and (2) identify clinical and demographic characteristics predicting initiation of β-blocker therapy. Methods: A retrospective cohort of US employed, commercially insured individuals was assembled using de-identified enrollment files, medical claims, and pharmacy claims from 2007 to 2009. Inclusion criteria were the following: (1) type 2 diabetes, (2) ≥18 years old, (3) continuous eligibility, (4) MI. Multivariable logistic regression with adjusted odds ratios (ORadj) using manual backward elimination was used to identify predictors of β-blocker initiation within 30 days of discharge from index hospitalization. Results: Of 341 T2DM patients, 167 (49.0%) were new users and 174 (51.0%) were nonusers of β-blockers within 30 days of post-MI hospital discharge. Patients on a calcium channel blocker (ORadj 2.63) and patients taking 1 to 5 medications (ORadj 3.59) were more likely to initiate β-blockers post-MI. Patients with heart failure (ORadj 0.45) or an arrhythmia (ORadj 0.44) were less likely to initiate β-blockers as well as patients with renal failure not taking a diuretic (ORadj 0.17). Conclusions: These results confirm previous findings that β-blockers are underutilized in T2DM patients post-MI. Predictors from the regression model can guide future research investigating how this deviation from guidelines is attributed to prescriber versus patient behavior.

Initiation of β-blocker therapy and depression after acute myocardial infarction

Although β-blockers reduce mortality after acute myocardial infarction (AMI), early reports linking β-blocker use with subsequent depression have potentially limited their use in vulnerable patients. We sought to provide empirical evidence to support or refute this concern by examining the association between β-blocker initiation and change in depressive symptoms in AMI patients. Using data from 2 US multicenter, prospective registries of AMI patients, we examined 1-, 6-, and 12-month changes in depressive symptoms after the index hospitalization among patients who were β-blocker-naïve on admission. Depressive symptoms were assessed using the validated 8-item Patient Health Questionnaire (PHQ-8), which rates depressive symptoms from 0 to 24, with higher scores indicating more depressive symptoms. A propensity-matched repeated-measures linear regression model was used to compare change in depressive symptoms among patients who were and were not initiated on a β-blocker after AMI. Of 3,470 AMI patients who were β-blocker-naïve on admission, 3,190 (91.9%) were initiated on a β-blocker and 280 (8.1%) were not. Baseline PHQ-8 scores were higher in patients not initiated on a β-blocker (mean 5.78 ± 5.45 vs 4.88 ± 5.11, P = .005). PHQ-8 scores were progressively lower at 1, 6, and 12 months in both the β-blocker (mean decrease at 12 months 1.16, P < .0001) and no-β-blocker groups (mean decrease 1.71, P < .0001). After propensity matching 201 untreated patients with 567 treated patients, initiation of β-blocker therapy was not associated with a difference in mean change in PHQ-8 scores at 1, 6, or 12 months after AMI (absolute mean difference with β-blocker initiation at 12 months of 0.08, 95% CI -0.81 to 0.96, P = .86). Initiation of β-blocker therapy after AMI was not associated with an increase in depressive symptoms. Restricting β-blocker use because of concerns about depression appears unwarranted and may lead to undertreatment of AMI patients.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Patterns of β-blocker initiation in patients undergoing intermediate to high-risk noncardiac surgery

Based on 2 small randomized controlled trials (RCTs) from the 1990s, β-blockers were promoted to prevent perioperative cardiac events in patients undergoing noncardiac surgery. In 2008, a large RCT (POISE trial) showed an increased mortality risk associated with perioperative β-blockade, raising concerns about an extensive β-Blocker use. The objective of the study is to examine patterns of β-Blocker initiation among patients undergoing noncardiac elective surgery in the US. From a large, nationwide US health care insurer, we identified patients ≥18 years old who underwent moderate- to high-risk noncardiac elective surgery between 2003 and 2012 and initiated a β-Blocker within 30 days before surgery. We evaluated temporal trends and assessed the impact of the POISE trial on perioperative β-Blocker initiation. We also evaluated patient characteristics and examined the effect of temporal proximity to surgery on the likelihood of β-Blocker initiation. Of 499,752 patients undergoing surgery, 9,014 (18 per 1,000 patients) initiated a β-Blocker. β-Blocker initiation increased from 12 per 1,000 patients in 2003 to 23 before POISE, after which it decreased to 14 by December 2012 (P = .0001). β-Blocker initiation remained relatively high among patients undergoing vascular surgery or with Revised Cardiac Risk Index score ≥ 2. Proximity to surgery was highly predictive of β-Blocker initiation (odds ratio 3.34, 95% CI 3.17-3.51). After a period of a rapidly increasing trend, perioperative β-Blocker initiation decreased sharply in the second half of 2008 and continued to decrease afterwards. β-Blocker initiation remained relatively high in patients with Revised Cardiac Risk Index score ≥2 and in those undergoing major vascular surgery.

Perioperative β-Blocker Therapy.

of the Clinical Problem Routine use of β-blockers to prevent cardiac complications related to noncardiac surgery began in the 1990s after the publication of 2 influential randomized clinical trials (RCTs).1,2 Responding to this evidence, a 2002 ACC/AHA guideline published a strong recommendation for starting β-blockers in high-risk patients undergoing vascular surgery and stated that thiswas also reasonable inmoderateto high-risk patients undergoingmajor noncardiac surgery. Although several subsequent studies of perioperative β-blockade were less favorable, a 2006 ACC/AHA guideline expanded its recommendations for perioperative β-blockade to include patients undergoing intermediateand high-risk procedures and stratified the strengthof its recommendations according to the presenceofmultiple clinical risk factors. Studiespublished in the following years provided conflicting evidence regarding perioperativeβ-blockade,3,4anda2009ACC/AHAupdatedowngraded its recommendations for initiationof β-blockers inhigh-riskpatientswith coronary disease or cardiac ischemia on preoperative testing before vascular surgery and advised against the initiation of highdose β-blockers in the absence of dose titration. Followingpublication of this guideline, evidence emerged that data from2majorRCTs (andmultipleother trials by the samegroup of investigators)were suspect.5 Ameta-analysis of 9RCTs (that excludeddata fromthesuspect trials)6 andapropensity-matched retrospective cohort analysis of 136 745 patients7 reached conflicting conclusions. Characteristics of the Guideline Source The ACC and AHA funded development of the guideline without commercial support (Table).8Theguidelinewritingcommitteemembers volunteered their time and disclosed their industry relationshipsbeginning 1 yearprior to their involvement.Bydesign, themajority of the committee had no conflicts of interest, but 2members were required to recuse themselves from voting on the section on perioperative β-blocker therapy because of industry relationships. The ACC/AHA Task Force commissioned an independent evidence review committee (ERC) to perform a systematic review of the literature on perioperative β-blockade. None of the 7 ERC members had a relevant relationship with industry. The guideline was

Preoperative β-blockers do not improve cardiac outcomes after major elective vascular surgery and may be harmful

Routine initiation β-blocker medications before vascular surgery is controversial due to conflicting data. The purpose of this analysis was to determine whether prophylactic use of β-blockers before major elective vascular surgery decreased postoperative cardiac events or mortality. The Society for Vascular Surgery Vascular Quality Initiative (SVS-VQI) data set was used to perform a retrospective cohort analysis of infrainguinal lower extremity bypass (LEB), aortofemoral bypass (AFB), and open abdominal aortic aneurysm (AAA) repair patients. Chronic (>30 days preoperatively) β-blocker patients were excluded, and comparisons were made between preoperative (0-30 day) and no β-blocker groups. Patients were risk stratified using a novel prediction tool derived specifically from the SVS-VQI data set. Propensity-matched pairs and interprocedural specific risk stratification comparisons were performed. End points included in-hospital major adverse cardiac events (MACEs), including myocardial infarction (MI; defined as new ST or T wave electrocardiographic changes, troponin elevation, or documentation by echocardiogram or other imaging modality), dysrhythmia, and congestive heart failure, and 30-day mortality. The study analyzed 13,291 patients (LEB, 68% [n = 9047]; AFB, 11% [n = 1474]; and open AAA, 21% [n = 2770]); of these, 67.7% (n = 8999) were receiving β-blockers at time of their index procedure. Specifically, 13.2% (n = 1753) were identified to have been started on a preoperative β-blocker, 54.5% (n = 7426) were on chronic β-blockers, and 32.3% (n = 4286) were on no preoperative β-blockers. Among the three procedures, patients had significant demographic and comorbidity differences and thus were not combined. A 1:1 propensity-matched pairs analysis (1459 pairs) revealed higher rates of postoperative MI with preoperative β-blockers (preoperative β-blocker relative risk, 1.65; 95% confidence interval, 1.02-2.68; P = .05 vs no β-blocker), with no difference in dysrhythmia, congestive heart failure, or 30-day mortality. When stratified into low-risk, medium-risk, and high-risk groups within each procedure, all groups of preoperative β-blocker patients had no difference or higher rates of MACEs and 30-day mortality, with the exception of high-risk open AAA patients, who had a lower rate of MI (odds ratio, 0.35; 95% confidence interval, 011-0.87; P = .04). Exclusive of high-risk open AAA patients, preoperative β-blockers did not decrease rates of MACEs or mortality after LEB, AFB, or open AAA. Importantly, exposure to prophylactic preoperative β-blockers increased the rates of some adverse events in several subgroups. Given these data, the SVS-VQI cannot support routine initiation of preoperative β-blockers before major elective vascular surgery in most patients.

Learning from mistakes in clinical practice guidelines: the case of perioperative β-blockade

For more than two decades, the role of β-blockers in preventing cardiac complications after surgery has been among the most hotly contested and controversial topics in medical practice. Based on...

Study design for the “effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion” (METOCARD-CNIC): A randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segment elevation myocardial infarction

Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI.