Abstract
Background:
The selection of β-blocker for survivors after primary intervention due to acute ST-elevation myocardial infarction seems crucial to improve the outcomes. However, rare comparison data existed for these patients. We aimed to compare the effectiveness of selective β-blockers to that of carvedilol in patients treated with primary intervention.
Methods and results:
Among the 1,485 patients in the “INTERSTELLAR” registry between 2007 and 2015, 238 patients with selective β-blockers (bisoprolol, nebivolol, atenolol, bevantolol, and betaxolol) and 988 with carvedilol were included and their clinical outcomes were compared for a 2-year observation period. In the clinical baseline characteristics, the unfavorable trends in the carvedilol group were high Killip presentation, lower ejection fractions, smaller diameters, and longer lengths of deployed stents. Although mortality (2.5% vs. 1.7%; p = 0.414) and the rate of stroke (0.8% vs. 0.6%; p = 0.693) were not different between groups, the rate of recurrent myocardial infarction (4.6% vs. 1.2%; p = 0.001) and of target vessel revascularization (4.2% vs. 0.9%; p < 0.001) were lower in the carvedilol group. After eliminating the difference by propensity matching, the similar outcome result was shown (all-cause death, 0.6% vs. 1.0%, p = 0.678; stroke, 0.6% vs. 1.2%, p = 0.479; myocardial infarction, 5.0% vs. 1.2%, p = 0.003; target vessel revascularization, 4.5% vs. 0.7%, p < 0.006) for 595 matched populations. The use of carvedilol was also determined to be an independent predictor for recurrent myocardial infarctions (hazard ratio = 0.305; p = 0.005; 95% confidence interval = 0.13-0.69).
Conclusion:
Use of a carvedilol in ST-segment myocardial infarction survivor is associated with lower recurrent myocardial infarction events. Thus, it might be the better choice of β-blocker for secondary prevention in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention.
Keywords
Introduction
Although the dependence on β-blocker treatment is decreasing in the primary percutaneous coronary intervention (PCI) era, it is still regarded as a cornerstone medication after primary PCI following a presentation of ST-elevation myocardial infarction (STEMI). The 2013 American College of Cardiology Foundation and the American Heart Association Guidelines (ACCF/AHA) and the 2017 European Society of Cardiology (ESC) STEMI Guidelines still recommend the routine oral treatment with β-blockers for patients who underwent primary PCI during hospital stay, if there is no contraindication.1,2 However, evidence supporting the advantages of β-blockers in reducing mortality were mostly confined to the pre-reperfusion era.3–5 Nevertheless, a recent meta-analysis demonstrated the favorable outcomes of β-blockers for the prevention of recurrent myocardial infarctions (MI) in both the reperfusion and the pre-reperfusion eras. 6 We postulated that the efficacy for prevention of MI would differ, depending on the type of β-blocker, in survivors of STEMI. The non-selective β-blocker, carvedilol, has theoretically more benefits than the selective β-blockers, such as vasodilation and antiproliferative properties of the α and β2 receptor blockade reduce the possible loss of cardiac output and/or facilitate small vessel dilatation. 7 Thus, we compared the outcomes between selective β-blocker and the carvedilol in a registry of STEMI patients.
Method
Study design and populations
We used the information from the INcheon-Bucheon cohorT of patients undERgoing primary PCI for acute ST-Elevation myocardiaL infARction (INTERSTELLAR) registry.8–12 The INTERSTELLAR registry, a record of a four-region hospital-based patients who underwent primary PCI for acute STEMI, was designed to track the outcomes. This registry has reflected the real-world clinical practice of primary PCI being solely treated with second-generation drug-eluting stents and is open for enrollment to all populations, eliminating any investigator’s selection. The exclusion criteria for registry enrollment were as follows: previous history of diagnosis and treatment of coronary artery disease (CAD), cardiomyopathy, moderate or greater severity valvulopathy, pericardial disease, or congenital heart disease.
Between 2007 and 2015 from the INTERSTELLAR registry cohort, a total of 1,485 patients’ clinical data and medication status were retrospectively reviewed for comparing the outcomes according to the types of β-blockers. Although the previous guidelines for the management of STEMI from the 2013 ACCF/AHA task force recommended β-blocker initiation within the first 24 hours, the newest version of guidelines from 2017 ESC omitted the emphasis on initiation timing and has recommended the wide use during hospital stay. Thus, we excluded the in-hospital deaths (58 deaths; 3.9%) among the INTERSTELLAR registry (Figure 1). In the study period, decision of initiation, doses of β-blockers during hospitalization, and the titration strategies of medications were at the physicians’ discretion. Among the survival of patients who underwent primary PCI, 106 (7.13%) patients were discharged without β-blockers, while a total of 1,321 patients were prescribed β-blockers at discharge. Although the previous report demonstrated only a 2-7% changed in β-blocker dosing over a period of years post MI, 13 there were chances of dose change in their first outpatient visit (mean 11.1 ± 9.9 days after discharge). Thus, evaluation of medication status was extended on that day. A total of 45 patients (3.4%) out of 1,321 patients, who were prescribed β-blocker at the time of discharge discontinued their medication due to intolerance, hypotension or bradycardic episode and 50 (3.7%) patients had changed their β-blockers from carvedilol to selective (7 patients, 0.52%) or selective to carvedilol (43 patients, 3.2%). After excluding the patients mentioned above, 1,226 patients were enrolled in this review and they were divided into the group with selective β-blocker medication (n = 238; 19.4%) and the group with the carvedilol (n = 988; 80.6%). The study protocol was reviewed and approved by the Institutional Review Board in Sejong General Hospital (Approval No. 1809) and all study subjects provided written informed consents.
Flowchart of patient enrollment.
Selective versus non-selective (carvedilol) β-blockers
The prescribed β-blockers were listed as the following: atenolol (n = 9; 0.7%), bevantolol (n = 11; 0.9%), bisoprolol (n = 142; 11.6%), nebivolol (n = 70; 5.7%), and betaxolol (n = 6; 0.5%) were assigned to the selective β-blocker group, while carvedilol (n = 988; 80.6%) was assigned to the other group. We allowed the use of carvedilol sustained-release (SR) form and 26 patients were prescribed SR type of carvedilol (2.5% out of patients prescribed carvedilol) at discharge. 14
Endpoint determination and data acquisition
The primary endpoint was the rate of recurrent MI as the efficacy indicator for β-blockers of secondary prevention. The secondary endpoint was composite major adverse cardiovascular and cerebrovascular event (MACE), which was defined as all-cause mortality, recurrent MI, stroke, and ischemia-driven target vessel revascularization (TVR) during the follow-up period. Among the patients with multiple cardiovascular and cerebrovascular events, only the first event was considered for analysis. Electronic medical record review and/or standardized telephone interviews were allowed for this study.
The patients’ medication status, including the dose and the types of β-blockers was analyzed at the time of discharge and at the time of the first outpatient clinic visit day. To evaluate the relationship between the medication dose and the outcome, we regarded the each medication’s target full dose as follows: atenolol, 100 mg/day; bevantolol, 200 mg/day; bisoprolol, 10 mg/day; nebivolol, 10 mg/ day; betaxolol, 20 mg/day; and carvedilol, 50 mg/day (or 64 mg/day for sustained releasing form of carvedilol).15–20
Data analysis and statistical methods
Continuous data are expressed as the mean ± standard deviation. The baseline characteristics of the selective β-blocker group versus carvedilol were compared using the two-sample t test or Mann–Whitney U test for continuous variables and Pearson’s Chi-square or Fisher’s exact tests for categorical variables. A Kaplan–Meier curve was drawn in for the recurrent MI and MACE for the whole and the matched populations. Univariate analyses were performed on each of the variables with respect to the primary endpoint, recurrent MI. Cox regression analysis was performed to quantify the relationships between the time to MI event and each potential risk factor including the age, sex, high Killip Class (Class 3 or 4) on admission, cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, and smoking), angiographic and procedural factors (multi-vessel coronary disease, length of deployed stent, and diameter of stent), and cardiovascular medications (use of potent antiplatelet agents, type of β-blockers, renin-angiotensin system (RAS) inhibitors, and statins). Multivariate Cox regression analysis of the associated factors (p < 0.2 on univariate Cox analysis) was performed to determine the independent predictors for a 2-year MI event.
As the β-blocker treatment strategy was not randomized, a propensity score was used to adjust predisposition and selection bias. Matching algorithm for propensity was the nearest neighbor and the caliper width was 0.3 SD. The patients were selected by 1:3 matching due to the difference in population numbers and covariates were chosen among the variables with p < 0.20 in Table 1. For checking the balance between groups after matching, the absolute standardized difference and the p-value were used. Propensity score matching was performed by package MatchIt of R program. Statistical Package for the Social Sciences (SPSS 18.0; SPSS Inc., Chicago, IL, USA), R program (version 3.4.4), and SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA) were used to perform statistical evaluations and p-values <0.05 were considered statistically significant.
Characteristics of total and matched population between selective β-blockers and carvedilol.
BP: blood pressure; ER: emergency room; bpm: beat per minute; BMI: body mass index; WBC: white blood cells; AST: aspartate transaminase; ALT: alanine transaminase; BUN: blood urea nitrogen; CK-MB: creatine kinase-MB; LVEDD: left ventricle end diastolic dimension; E/E′: the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E′); EF: ejection fraction; LV dysfunction: left ventricular dysfunction defined as EF < 35%; 1VD: one vessel coronary artery disease; 2VD: two vessel coronary artery disease; 3VD: three vessel coronary artery disease; IRA: infarction-related artery; LM: left main; LAD: left anterior descending; LCX: left circumflex artery; RCA: right coronary artery; others, other second generation stent, potent antiplatelet; patient who prescribed either by dual antiplatelet therapy plus cilostazol or dual antiplatelet therapy with ticagrelor/prasugrel; RAS inhibitor: renin-angiotensin system inhibitor; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker.
Results
Baseline characteristics of the whole patient population
Table 1 shows baseline clinical, laboratory, and echocardiographic characteristics of whole and matched population. The overall mean age of whole population was 59.9 ± 13.0 (range: 26-94) years. The age and sex, presence of hypertension, diabetes, and status of smoking were similar between the groups. However, in the carvedilol group, there were more patients with hypercholesterolemia (15.1% vs. 21.1%; p = 0.040) and presentation with Killip Class 3 to 4 (6.4% vs. 11.8%; p = 0.017). The laboratory findings, taken from the emergency room (ER), revealed that the creatinine levels tended to be higher in the carvedilol group (1.0 ± 0.8 vs. 1.1 ± 1.1; p = 0.053, respectively) and the troponin-T level was also significantly higher (4.0 ± 25.8 vs. 11.0 ± 36.0; p = 0.002). In addition, the early diastolic transmitral velocity-to-early myocardial velocity ratio measured by tissue Doppler (E/E′) showed a greater tendency (12.1 ± 4.8 vs. 12.8 ± 7.2; p = 0.191) and the ejection fraction (EF) showed a lower tendency to the carvedilol group (50.2 ± 11.5 vs. 48.6 ± 11.3; p = 0.052).
Angiographically, the left anterior descending artery was the most common site of infarction related artery in both groups (51.7% and 47.9%; p = 0.292). However, more patients in the selective group had left circumflex artery infarction (14.7% vs. 9.7%; p = 0.025). The delivered stent diameter tended to be smaller (3.5 ± 1.5 mm vs. 3.3 ± 0.4 mm; p = 0.060) and significantly longer (25.1 ± 9.7 mm vs. 27.2 ± 11.9 mm; p = 0.006) in the carvedilol group.
Dual antiplatelet therapy was used for all patients at discharge, and more than 90% of patients were prescribed clopidogrel-based dual antiplatelet regimen, while less than 10% of patients were treated with newer antiplatelets (ticagrelor or prasugrel) in both groups (7.1% vs. 9.9%; p = 0.184). However, a higher trend for additional use of cilostazol was noted in the carvedilol group (16.3% vs. 21.9%; p = 0.065). Although there were more cases of hyperlipidemia in the carvedilol group, statin was prescribed more to the selective group (92.0% vs. 85.2%; p = 0.006) and a similar rate of RAS inhibitor was prescribed (80.7% and 82.4%; p = 0.536). Angiotensin-converting enzyme inhibitors were dominantly prescribed to the selective group (68.2% vs. 55.4%; p < 0.001), while more angiotensin receptor blockers were prescribed to the carvedilol group (11.0 vs. 28.2; p < 0.001).
Baseline characteristics of the propensity-matched patient population
A total of 595 patients were matched at 1:3 distribution after propensity score matching.
Table 1 also shows the adjusted parameters of disparities in the baseline clinical, laboratory, echocardiographic, and angiographic characteristics between the selective and the carvedilol groups. No significant difference was observed between the groups. No patients with ticagrelor or prasugrel were chosen for the matched population.
Outcomes of whole and matched populations
Although mortality (2.5% vs. 1.7%; p = 0.414) and the rate of stroke (0.8% vs. 0.6%; p = 0 0.693) were not different between groups, the rate of recurrent MI (4.6% vs. 1.2%; p = 0.001) and of target vessel revascularization (4.2% vs. 0.9%; p < 0.001) were lower in the carvedilol group. After eliminating the difference by propensity matching, the similar outcome result was shown (all-cause death, 0.6% vs. 1.0%, p = 0.678; stroke, 0.6% vs. 1.2%, p = 0.479; MI, 5.0% vs. 1.2%, p = 0.003; target vessel revascularization, 4.5% vs. 0.7%, p < 0.006) for 595 matched populations. A composite of MACE was observed more in the selective group than the carvedilol group in whole population (10.5% vs. 5.2%; p = 0.003) and matched population (9.5% vs. 4.1%; p = 0.006). The Kaplan–Meier’s survival curves were drawn for MI, and MACE for the whole and the matched populations (Figure 2). Significant better outcomes were observed toward the carvedilol group for the whole and the matched populations (log rank p-value = 0.001 and 0.003 for MI; 0.003 and 0.006 for MACE). Among the variables having a trend toward significance (deployed stent diameter, p = 0.060, hazard ratio (HR): 0.417, 95% CI: 0.16-1.03; statin treatment, p = 0.137, HR: 4.549, 95% CI: 0.61-33.4; and use of carvedilol, p = 0.002, HR: 0.282, 95% CI: 0.12-0.63), the use of carvedilol was an independent predictor of MI prevention in the multivariate Cox regression analysis (p = 0.005; HR: 0.305; 95% CI: 0.13-0.69). Subgroup analysis was performed for MI prevention efficacy comparison between clinical risk factors and each of β-blocker medications (Figure 3). Of note, the use of carvedilol showed favorable HR (0.28 for whole population and 0.23 for matched population) compared to the use of nebivolol or bisoprolol in the rate of recurrent MI.
(a) Kaplan–Meier curves for the acute myocardial infarction according to the use of the selective β-blockers versus carvedilol in whole population. (b) Kaplan–Meier curves for the combined MACE (myocardial infarction, target vessel revascularization, all-cause death, and stroke) in whole population. (c) Kaplan–Meier curves for the acute myocardial infarction according to the use of the selective β-blockers versus carvedilol in matched population. (d) Kaplan–Meier curves for the combined MACE in matched population.
Hazard ratios (95% confidence intervals) for 2 years recurrent myocardial infarction between traditional clinical risk factors and β-blockers. Blue boxes and bars indicate HRs (95% CI) of total cohorts and red ones indicate HRs (95% CIs) of propensity score-matched population.
Vital signs and dosage of β-blockers in the patient population
Patients’ vital signs were recorded at ER at the time of admission before β-blocker therapy and those were not different between the groups. The patients would visit their outpatient clinic at mean 11.0 ± 9.8 days after discharge. The doses of β-blockers were available to review except for two patients in the selective (99.2%) and seven in the carvedilol group (99.3%). The vital signs were available for assessment at outpatient department in 185 patients (77.7%) and 719 patients (72.6%) in the selective and the carvedilol groups, respectively. The systolic and the diastolic blood pressure (BP) measurements, at the outpatient clinic, were slightly higher in the carvedilol group (systolic BP, 114.8 ± 17.9 vs. 118.1 ± 18.1; p = 0.028 and diastolic BP, 68.8 ± 11.1 vs. 71.7 ± 10.8; p = 0.001). However, the heart rate was slightly lower in the carvedilol group (70.1 ± 14.1 vs. 66.2 ± 26.6; p = 0.023).
In the selective group, the patients were discharged with 26.0% ± 17.4% of each medication’s target full dose (28.5 ± 13.7 mg of atenolol; 84.1 ± 47.8 mg of bevantolol; 2.2 ± 1.7 mg of bisoprolol; 2.9 ± 1.3 mg of nebivolol; and 11.7 ± 4.1 mg of betaxolol) while 15.3% ± 11.4% of the target dosage (carvedilol, 7.7 ± 5.6 mg) was prescribed at discharge to the carvedilol group (p < 0.001). At the first outpatient clinic visit, 8% of the selective group and 18.5% of the carvedilol group had their doses up-titrated and the remaining patients had maintained the same dose of β-blockers. Nonetheless, the discharge dose and the first outpatient clinic dose of β-blockers were not associated with the occurrence of recurrent MI (HRs, 0.99 and 0.98; p-value, 0.57 and 0.31; 95% CI, 0.95-1.02 and 0.95-1.01) nor MACE (HRs, 1.00 and 0.99; p-value, 0.55 and 0.28; 95% CI, 0.98-1.01 and 0.98-1.01).
Discussion
The core finding of this study was that carvedilol might have an advantage over selective β-blockers in the secondary prevention of recurrence in STEMI patients who underwent primary PCI.
Evidences of mortality benefits of β-blockers in pre-reperfusion versus reperfusion era
The β-blocker treatment was regarded as a cornerstone medication after MI presentation and it was supported by the strong evidence from randomized controlled trials and meta-analysis. 21 Thus, the European and American Guidelines22,23 were recommending the β-blocker treatment during the hospitalization if there was no contraindication. However, many questionable outcomes of the β-blockers also presented along with the development of routine primary PCI for STEMI patients. 24 Indeed, the earlier trials represented the pre-reperfusion era; BHAT (β-blocker Heart Attack Trial), 5 MIAMI (Metoprolol in Acute Myocardial Infarction), 4 and ISIS-1 (First International Study of Infarct Survival) 3 showed a favorable trend toward the use of β-blockers with propranolol, metoprolol, and atenolol, respectively. Since the beginning of the reperfusion era, the COMMIT randomized trial 25 was designed in which half of the patient population underwent reperfusion therapy. However, it failed to prove mortality reduction (Odds ratio (OR), 0.99; 95% CI, 0.92-1.05; p = 0.69). 25 Other similar studies, which aimed to prove the advantage of β-blocker, also showed disappointing results. Bangalore et al. 6 found that studies in the pre-reperfusion era demonstrated a mortality benefit with β-blockers, however studies in the reperfusion era have not demonstrated a mortality benefit. Since most of the current guidelines recommend the routine use of β-blockers for survivors of acute MI patients,22,23 it would be impossible to conduct randomized controlled trial to demonstrate the mortality benefit of β-blocker in the primary PCI era. However, a large-sized registry data demonstrated an equal risk of death with or without the use of β-blockers, especially in the absence of heart failure or systolic dysfunction. 24
MI prevention
Although the randomized trials or large-sized registry data failed to prove benefits on the survival aspect, the usefulness of MI prevention was still observed for the pre-reperfusion and reperfusion strategies.26,27 Carvedilol showed a favorable trend for reducing reversible myocardial ischemia, which was confirmed by exercise thallium-201 scan 6 months after first presentation (p = 0.07), and it made significantly lower cardiac events (p = 0.04) compared to placebo in the earlier thrombolytic era. 27 The Capricorn study randomized trial 15 using carvedilol was performed on the patients with left ventricular dysfunction after acute MI presentation with a half of the patients undergoing thrombolytic therapy. The mortality rate (12% for carvedilol and 15% for placebo; p = 0.031), as well as non-fatal MI (3% in carvedilol and 6% in placebo; p = 0.014), was lower than the placebo group. Although, the COMMIT randomized trial 25 failed to demonstrate mortality reduction, metoprolol group had fewer recurrent MI (2.0% vs. 2.5%; OR, 0.82; 95% CI, 0.72-0.92; p = 0.001). It should be highlighted that the role of β-blockers in the reperfusion era would be the secondary prevention of MI for this reason. Cardiac protection, achieved by lowering the heart rate, might be required after STEMI events for patients who underwent primary PCI, though cardiac output should not be reduced by the medication use.
Selective versus non-selective β-blocker in congestive heart failure
The patient populations in randomized trials for congestive heart failure were similar to that of MI studies in the pre-reperfusion era.5,28,29 Although most of the patients presenting with acute MI needed to treat for heart failure management in advance, some of the patient subsets required heart failure management from presentation. Approximately 20-25% of the patients in our registry had left ventricular dysfunction (EF < 40%). Substantial evidence proving the benefits of β-blockers were observed for the patient subset represented by left ventricular dysfunction and/or congestive heart failure,18,30,31 justifying the guidelines’ strong recommendation of β-blocker use.32,33 Importantly, carvedilol showed benefits of preventing mortality against metoprolol in a direct comparison (COMET trial 34 ; HR, 0.83; 95% CI, 0.74-0.93; p = 0.0017). This significance was mainly derived from the vascular origins that the fatal or the non-fatal MI (HR, 0.70; 95% CI, 0.50-0.99) and the death from stroke (HR, 0.33; 95% CI, 0.18-0.62) were significantly better in the carvedilol medication group. 34
Selective versus non-selective β-blocker in MI
The first randomized trial of β-blockers for MI patients was published in the 1960s, and a large-scaled meta-analysis was reported in 1999. 21 In this meta-analysis, cardioselectivity was associated with a non–significant trend toward reduced benefit. Among the non-selective β-blockers including acebutolol, alprenolol, carvedilol, labetalol, oxprenolol, pindolol, propranolol, sotalol and timolol, the use of propranolol and timolol was most recommended with substantial reduction in the odds of death. However, only one study for carvedilol, with small populations, was included in this study. A recent meta-analysis compared the non-selective β-blocker (carvedilol) to the β1-selective blockers and the mortality benefit was demonstrated by the fixed-effect model although carvedilol only showed trends toward reducing non-fatal MI. 35 Although bisoprolol, nebivolol, and metoprolol are the most comparable selective blockers against carvedilol, the use of metoprolol is characteristically very low in South Korea, in contrast the use of bisoprolol is higher. Recently, carvedilol with nebivolol was regarded as a vasodilating β-blocker and compared with other selective β-blocker in a multicenter cohort study and the composite clinical outcome including cardiac death or MI was better in the vasodilating group. 36 Considering that the majority of patients in the vasodilator group were prescribed carvedilol (91.8%) and, in contrast, the majority of the non-vasodilatory group was prescribed bisoprolol (96.4%), their comparison may be regarded as carvedilol versus bisoprolol. Similar to their research, bisoprolol accounted for most of the β-blockers in group of selective β-blocker group, whereas we assigned nebivolol to this group as the counter part of the carvedilol group. Although, nebivolol theoretically has additive vasodilator effect for STEMI patients compared to the conventional selective β-blocker, clinical outcome data were insufficient. Our subgroup analysis indicated no significant benefit compared to carvedilol (Figure 3).
The mechanism supporting the superiority of carvedilol is not clearly proven. However, some contributory characteristics can be inferred. First, some of the norepinephrine releasing activity can result in prothrombotic effects and it is known to be regulated by the prejunctional β2 adrenergic receptor. Thus, an additional β2 blockade could effectively reduce the activity compared to selective β1 blockers. 37 Second, additive α-receptor blocking properties could reduce BP mainly through vasodilation, whereas other selective β-blockers are known to reduce cardiac output. 38 Third, carvedilol exhibits favorable metabolic effects and antioxidative and nitric oxide-releasing capacities. 39
Limitation
This study has some limitations. First, the analysis was conducted on non-randomized registry data. Some important baseline characteristics were, therefore, different between the groups. Nevertheless, we aimed to analyze both the real baseline characteristics after STEMI presentation and the matched population to avoid making a possible selection bias. Second, the in-hospital use of β-blockers was not evaluated. Third, unlike the carvedilol group, population was small in the selective group and patients with heterogeneous medications were included. In addition, metoprolol, one of the most commonly used selective β-blocker, was not included in our population. Fourth, patients’ medication status was not fully traced during the entire study period. However, while other observational studies used the medication profile only at the time of discharge,36,40–43 we extended the review of the data from the first outpatient clinic. Finally, current study was analyzed from regional base and single race/ethnicity population. Perhaps diversity in cultural or genetic differences was not been included in the current study.
Conclusion
Use of a carvedilol in ST-segment elevation MI survivor is associated with lower recurrent MI events. Thus, it might be the better choice of β-blocker for secondary prevention in STEMI patients treated with primary PCI.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Chong Kun Dang Research Grant.
