Editorials
Oral β-Blocker Therapy in Acute Myocardial Infarction
2019 Volume 83 Issue 2 Pages 281-282
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2019 Volume 83 Issue 2 Pages 281-282
Randomized controlled trials (RCT) and meta-analyses conducted in the pre-reperfusion era have demonstrated beneficial effects of oral β-blocker therapy on survival in patients with acute myocardial infarction (AMI).1–3 Current clinical practice guidelines recommend oral β-blockers for secondary prevention in AMI patients with reduced systolic left ventricular function or heart failure, in the absence of contraindications (class I).4,5 It is unclear, however, whether oral β-blocker therapy is effective in uncomplicated AMI patients who have undergone percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) after AMI and received state-of-the-art medication such as strong statins and renin-angiotensin-aldosterone system antagonists (RAAS antagonists). Furthermore, the optimal type, dose, and duration of β-blocker therapy are not clearly defined.
Article p 410
In this issue of the Journal, Hwang et al examine the association between oral β-blocker dose and 1-year risk of cardiac death after AMI using data from a multicenter, prospective registry, the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH).6 Eighty-three percent of patients were discharged on a β-blocker. Beta-blocker type and dose were chosen by the individual physician. The majority of patients received either bisoprolol or carvedilol. Patients discharged on a β-blocker were classified as low-dose or high-dose, according to the percent of target dose prescribed (<25%, ≥25%). The majority of patients were discharged on low-dose β-blockers. All patients in the study were compliant in maintaining the type and dose of β-blocker up to 1 year after discharge. The mean ejection fraction was 52%, and most patients received revascularization via either PCI or CABG (no β-blocker group, 77.1%; low-dose group, 94.6%; high-dose group, 91.2%; P<0.0001). Dual antiplatelet therapy was performed in >99% of patients, and most patients received RAAS antagonists and statins (RAAS antagonists/statins: 54.5/86.1% in no β-blocker group, 84.9/95.2% in the low-dose group, and 84.7/93.8% in high-dose group, P<0.0001). The rate of 1-year cardiac death was lower for patients discharged on β-blocker compared with no use of β-blockers. A significant dose-effect of β-blockers on heart rate reduction was observed (no β-blocker group, 3.7±20.5; low-dose group, 6.3±18.8; high-dose group, 8.7±19.9 beats/min; P<0.001), and significantly higher blood pressure reduction was observed in the high-dose group compared with the no β-blocker and the low-dose groups. There was no significant additional benefit, however, of high-dose β-blockers compared with low-dose β-blockers for risk of cardiac death.
The main mechanism of the beneficial effects of β-blockers in patients with AMI is considered to be attenuation of the myocardial oxygen demand by decreases in heart rate, blood pressure, and myocardial contractility.7 Although the hemodynamic effects of β-blockers are considered as dose dependent, observational studies reported that patients who had had AMI were being treated with lower doses of β-blockers than that used in clinical trials (Table).6–10 The discrepancy between the target dose and prescribed dose in the real-word patients is perhaps due to the adverse effects of β-blockers such as hypotension, bradycardia, coronary spasm, fatigue, depression, and metabolic disorders.11
| Target dose (mg/day) |
Percentage of β-blocker type used in patients discharged on a β-blocker (%) |
||||
|---|---|---|---|---|---|
| OBTEIN Study8 | IHCS Registry9 | CREDO-Kyoto AMI Registry10 |
KAMIR-NIH Registry6 |
||
| Metoprolol | 200 | 67.7 | 80.0 | – | 1.7 |
| Carvedilol | 50 | 24.3 | 10.0 | 90.2 | 44.4 |
| Bisoprolol | 10 | 2.8 | – | – | 48.3 |
| Atenolol | 100 | 3.8 | 7.0 | – | – |
| Propranolol | 16010 or 1808 | 0.2 | – | – | – |
| Nebivolol | 10 | – | – | – | 5.0 |
| Others | – | 1.1 | 3.0 | 9.8 | 0.6 |
| Percentage of patients prescribed low-dose† β-blocker of those discharged on a β-blocker |
– | 61.2 | 86.6 | 73.5 | 83.4 |
†Less than 25% of target dose.
The main finding of the present study suggesting no significant additional benefit of high-dose β-blockers compared with low-dose β-blockers for risk of cardiac death would be robust, because the baseline characteristics, severity of AMI, prevalence of early revascularization, and concomitant medications were remarkably similar between the low-dose and high-dose β-blockers groups. The fundamental question, however, is whether oral β-blocker therapy could improve clinical outcomes in contemporary uncomplicated AMI patients or not. The present study as well as several other observational studies have suggested the clinical benefit of β-blockers in patients with uncomplicated AMI,6,12,13 while we reported no benefit of β-blockers in ST-segment elevation AMI (STEMI) patients treated with primary PCI in the 2 Japanese large-scale observational studies.10,14 Selection bias for use of β-blockers is inevitable in these observational studies. The most striking difference between the present study and the 2 Japanese studies was the very low prevalence of no β-blocker use in the present study (17% vs. 56%12 and 62%14). Given that β-blocker in AMI is the guideline-recommended medication, very low prevalence of no β-blocker use might indicate that a large proportion of patients in the no β-blocker group were those who were deemed to have very poor prognosis, and in whom β-blocker was regarded as futile. It is noteworthy that patients in the present no β-blocker group less frequently received early revascularization and guideline-recommended medications. Indeed, in the CAPITAL-RCT trial, which is the only RCT exploring the effectiveness of an oral β-blocker in uncomplicated STEMI patients, the event rate for a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome at median 4-year follow-up was very low, and the event rate did not differ with regard to β-blocker use.15 The lack of a dose-response relationship for β-blockers in the present study might be explained very well, if β-blockers are not at all effective in preventing cardiovascular events in patients with uncomplicated AMI. A large RCT (REDUCE-SWEDEHEART: ClinicalTrials.gov NCT 03278509) is ongoing to evaluate the role of β-blocker after AMI in contemporary practice.
The authors declare no conflicts of interest.
