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Use of Beta-blockers in the Acute Phase of Myocardial Infarction: A Study of 86 Cases.

Markman Manuel; Chaves Ândrea; Markman Filho.Brivaldo.

Hospital Agamenon Magalhães
Recife-PE. Brasil.

Abstract
Introduction
Methods
Results
Discussion
Conclusions

Abstract
Background -  It is consensus that the use of beta-blockers (BB) in patients (pts) with acute myocardium infarction (AMI) diminishes morbi-mortality after hospital discharge. However, in the thrombolytic era it is questionable if these drugs may be beneficial during in-hospital stage.
Purpose - In-hospital evaluation of pts with AMI, using BB by mouth, regarding the appearance of angina/recurrent ischemia, re-infarction and arrhythmias.
Methods - A prospective study of 86 pts with AMI, divided into two groups: Group I) 43 pts using atenolol ( up to 100mg/day ), group II) 43 pts without BB. The inclusion criteria was AMI in the first 48 hours. Patients that need BB intravenously or with contra-indications to its use were excluded. Statistic analysis by Mantel-Hanzel and Fisher Exact did not show significative difference between the two groups regarding : age, sex, hypertension, diabetes mellitus, previous AMI, thrombolytic use, aspirin, ace inhibitors, previous use of BB, Killip class ( in admission ), ejection fraction ( ECHO ), multivessel disease ( CATH ) and AMI location.
Results -
tabla0.gif (1064 bytes)it was necessary to have BB dosage reduced in 17 pts (39%) and to have it discontinued in 2 pts (4%) due to side effects.
Conclusions - Beta-blockers are safe and reduce arrhythmias, but they do not improve in-hospital evolution regarding ischemic events when given orally.

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Introduction: The therapy with beta-blocker is advisable in myocardial postinfarction because it decreases the new ischemic events and, mainly, the long term mortality after discharge from hospital. Even in the thrombolytic era, the early use of intravenous (IV) beta-blocker managed to demonstrate benefits as to the decrease in the occurrence of recurrent infarction and ischemia, but without substantiating significant data as to improvement of ventricular function or additional decrease in mortality together with the use of thrombolytic agents (1). Its use orally in the infarction hospitalisation phase is routine in many cardiology Services, although the evidences of benefits against ischemic events, arrhythmias and early mortality are questionable both for the patients not submitted to thrombolytic therapy (2), and for the patients submitted to thrombolytic therapy who did not use beta-blocker IV in the first 12 hours of acute myocardial infarction (AMI).

The objective of this study is to evaluate the benefits and safety of the beta-blocker use, orally, in infarction patients as to the decrease in postinfarction angina, recurrence of infarction and sustained arrhythmias in the hospitalisation phase.

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Methods: Eighty six patients with myocardial infarction in the 48 hours from admission were prospectively evaluated until discharge from hospital and divided in two groups according to the order of arrival at the hospital, alternating for group I (treatment with atenolol) or group II (without beta-blocker treatment). The active group was given atenolol orally in the first 24 hours, until achieving the maximum dose of 100mg/day till the second day, or the maximum dose tolerated by the patient without the occurrence of severe bradycardia (Heart rate < 45) or hypotension (SBP < 90mmHg). The drug was discontinued in the occurrence of atrioventricular block (AVB) 2nd and 3rd degrees, appearance or worsening of left ventricular failure (LVF) or bronchospasm. The exclusion criteria were: infarction which started more than 48 hours before, formal contra-indications to beta-blocker use (cardiogenic shock, Killip III/IV, bronchial asthma, chronic occlusive pulmonary disease, atrioventricular block (AVB) 2nd and 3rd degrees) and when it was advisable to use the beta-blocker at the admission. Postinfarction angina was defined as chest pain after 24 hours of myocardial infarction (AMI) which disappeared or decreased with sublingual vasodilators, and recurrence of infarction through medical, electrocardiographic and enzymatic data (pain which did not cede with the use of vasodilators accompanied of new alterations in the ECG and new peak in the CKMB). The arrhythmias were evaluated during monitoring in the coronary unit, being taken into account only sustained supraventricular or ventricular tachyarrhythmias, including sinus tachycardia which persisted for more than 36 hours from the beginning of the AMI. The treated group (group I) was compared to the control as to the risk factors, age, sex, site of AMI, medical conditions at admission and use of medications, and statistical differences were not found among them (tables). The time elapsed between the beginning of the symptoms and the first medication (atenolol) was 15.4 hours and the average evaluation period until discharge from hospital was 12.5 and 10.5 days in groups I and II, respectively.

The statistical analyse were obtained with Mantel-Haenzel test and Fisher test, when appropriate.

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Results: The combined postinfarction angina / recurrent infarction data did not show significant statistical difference between groups I and II (05 and 09, respectively, p = 0.24). The treated group presented less arrhythmic events in relation to the control (02 and 12, respectively, p = 0.003), being 08 with sinus tachycardia, 01 atrial fibrillation (AF), 01 paroxysmal junctional tachycardia, 01 atrial tachycardia and 01 ventricular fibrillation (VF) (Tables).

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Results
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The treated group presented more hypotension in relation to the control (14 and 02, respectively, p = 0.009), but easily managed with the decrease of atenolol dose. Discontinuation was necessary in only 04 patients: 02 with LVF, 01 with fall in the arterial blood pressure and 01 with bronchospasm. There was need to use BB in 12 patients from group II due to: angina in 03, persistent sinus tachycardia in 08 and AF in 01 patient.

The drug was shown to be safe for it does not increase the incidence of advanced AVB or medical manifestations of LVF.

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Discussion: This study tried to demonstrate the short term results of oral BB therapy in infarction patients, which constitutes routine practice in many cardiology services, even if it is not preceded by early IV use.

The medical benefits in relation to the decrease of new early ischemic events (in the first 6 days of AMI), with the use of BB in the first hours (3.3 hours average) from the onset of AMI are still verified in the thrombolytic era with the TIMI II-B study (1).

The population of our study is constituted, in the greatest part, of patients who received thrombolytic therapy (53 of 86), treated with streptokinase and admitted in favourable medical conditions in the great majority (Killip class I, without previous AMI or advanced age and without predominance of previous AMI). The average time elapsed between the onset of the AMI and the first dose of atenolol was 15.4 hours. There were no benefits in relation to the combined data of angina and recurrence of infarction in the treated group (p = 0.24). The statistical analysis, however, showed ample variation in the confidence interval (0.12 to 1.86). Notwithstanding, even in the TIMI II-B study (1) when analysed the subgroup in conservative strategy, that is, without early invasive approach with primary angioplasty, which better corresponds to the characteristics of our population, the BB did not confirm differences in the reduction of ischemic events in 354 patients, compared to the 349 ones who did not make use evaluated in 6 days of AMI. Metanalysis of 31 studies (2) with IV BB in the prethrombolytic era showed reduction of 18% in recurrence of infarction (308 against 301 recurrences of infarction in the treated groups and control, respectively) in the evaluation of 0 to 7 days of AMI. Due to the small number of patients, our study does not allow comparative analysis for subgroups with and without use of streptokinase.

In the cases we have dealt with, we have observed a beneficial effect in the prevention of sustained tachyarrhythmias (12 cases in the control group and 2 cases in the treated group, p = 0.003), particularly in the persistent sinus tachycardia for more than 36 hours of AMI. The confidence interval of 95% also varied amply (0.01 - 0.64). A possible explanation for this variation in the confidence interval is found in the small number of patients studied, what decreases the power of the statistical analysis. The studies with BB orally, with short term evaluation of the AMI in the prethrombolytic era, did not confirm significant differences in the decrease of ventricular arrhythmias (2). When they were used IV, they demonstrated benefits in relation to the arrhythmias and, in the MIAMI study (3), a small difference was noticed in the incidence of ventricular fibrillation during the first days. Different from the majority of the previous studies, this work tried to evaluate not only the ventricular arrhythmias, but the supraventricular ones as well. The greater incidence of the latter in the control group caused the use of BB in these patients. Such an occurrence may account for the low incidence of ischemic events in this group. Two studies with IV BB in the AMI observed, as secondary data, protection against the occurrence of supraventricular arrhythmias, particularly against AF (4,5).

As regards the side effects, the drug turned out to be safe and well tolerated. Hypotension occurred in 14 patients in the treated group, versus 2 in the control group, which was easily solved with dose adjustment most of the times. This fact has been observed in the majority of studies with BB (6). Only 04 patients had their treatment discontinued: 02 through development of LVF, 01 with severe asthma and 01 patient presented arterial hypotension which was not corrected with volume reposition. Such effects were promptly solved with discontinuation of the drug.

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Conclusiones: The BB, when used orally in infarction patients was shown to be a safe drug, decreased supraventricular arrhythmias, but did not improve evolution during hospitalisation as to the occurrence of ischemic events.

Key words: beta-blockers, acute myocardium infarction.

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Bibliografía

1. The TIMI Study Group: Immediate Versus Deferred B-Blockade Following Thrombolytic Therapy in Patients With Acute Myocardial Infarction. Results of the TIMI II-B Study. Circulation 83:422-437, 1991.
2. Yussuf S et al. Beta-Blockade during and after miocardial infarction. An overview of the randomized trials. Prog Cardiovasc Dis 17:335, 1985.
3. The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction (MIAMI). A randomized placebo-controlled international trial. Eur Heart J 6:199, 1985.
4. Evemy KL, Pentecost BL: Intravenous and oral practolol in acute stages of myocardial infarction. Eur J Cardiol 7:391-398, 1978.
5. Yusuf S, Sleight P, Rossi PRF, et al: Reduction in infarct size, arrhytmias, chest pain, and morbidity by early intravenous beta-blockade in suspected acute myocardial infarction. Circulation 67 (pt2):32-41, 1983. 6. ISIS-1 (First International Study of Infarct Survival) Collaborative group. Randomized trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction. Lancet 2:57, 1986.

Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to coronary-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.

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Update
Nov/01/99


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