Considerable evidence supports the routine long term use of β blockers in patients who have had a myocardial infarction, with substantial benefits in terms of reduced mortality and morbidity. Short term β blockade immediately after acute myocardial infarction seems unlikely to be of major benefit unless treatment is continued long term. This finding contradicts recent suggestions that β blockers should be more commonly used intravenously in acute myocardial infarction.21
In fact, evidence strongly indicates that unless β blockers are continued long term, the benefits suggested by Owen21
will not be observed.
The benefits of β blockers on all cause mortality are impressive when compared with other frequently used long term treatments for the same patient group. Table shows the effects of different drugs on the number of patients that would need to be treated for 2 years to avoid one death—for example, after a myocardial infarction 42 patients would need to be treated with β blockers whereas 292 patients would need to be treated with antiplatelets.22
The number and length of long term trials showing a consistent benefit for β blockers in unselected patients after myocardial infarction suggest lasting benefits in this comparatively high risk group, and suggest that β blockers should be continued indefinitely.
Comparison of effect on mortality of different drugs
Have benefits from β blockade declined with availability of new treatments?
Our finding that β blockers benefit a broader group of patients after myocardial infarction supports the findings of the β blocker pooling project.23
Our finding also agrees with those of the cooperative cardiovascular project, which examined the medical records of 201
752 patients who had had a myocardial infarction.24
In that study, mortality was lower in every subgroup of patients treated with β blockade than in untreated patients. The findings of the cooperative cardiovascular project agree with our meta regression analysis, which found no evidence of a reduction in benefits from β blockade in more recent randomised trials. Indeed, rather than being overtaken by newer treatments, β blockers have a comparatively large effect in reducing mortality (table ).
Which β blocker?
Cardioselectivity was associated with a non-significant trend towards reduced benefit. The presence of an intrinsic sympathomimetic effect predicted a near significant reduction in benefits and thus drugs with this characteristic should be avoided. We found evidence to support the long term use of propranolol and timolol, the only two drugs indicated for prophylaxis after myocardial infarction in the British National Formulary. The use of either drug led to a substantial reduction in the odds of death, with narrow confidence intervals (fig ). In contrast, atenolol, which is commonly prescribed in secondary prevention, has been inadequately evaluated in this setting. Although similar efficacy may be achieved—we found no evidence that all β blockers are not equal—it cannot be presumed that the benefits from propranolol, timolol, and metoprolol will be achieved with other drugs.
Have benefits from intravenous β blockers declined over time?
It may be hypothesised that intervention with thrombolytic drugs and antiplatelets reduces the potential for patients to benefit from intravenous β blockade. The first international study of infarct survival25
was completed before the results of the second international study16
became available, and before the use of thrombolytic and antiplatelet treatment was established. In contrast, the comparison of early versus delayed β blockade in a large trial of thrombolysis in myocardial infarction was undertaken in patients who all received thrombolytic and antiplatelet treatment.17
Although the much larger first international study of infarct survival trial25
achieved a slightly larger reduction in the odds of death with β blockers, measurement error could not be excluded as an explanation for this difference, as indicated by the test for heterogeneity between the trials (Q=0.025, df=1, P=0.87). The thrombolysis in myocardial infarction trial did suggest that early use of intravenous β blockers could reduce the early risk of serious arrhythmias.
Are β blockers underused?
Concern has been voiced that β blockers are used in less than half of eligible patients after myocardial infarction,1–3
despite substantial benefits and generally low treatment costs. Concern that side effects affect the usefulness of β blockers must be tempered by the low yearly withdrawal from β blockers in the long term trials we reviewed. The clinical implications of our results are clear. New is not necessarily better, especially if the aim is to reduce mortality in patients after myocardial infarction. Furthermore, the underuse of β blockers in this group leads to a rate of avoidable death that should not be considered acceptable among those keen to practice evidence based medicine.
Renewed interest in β blockers, particularly in patients with heart failure,26–28
may lead to substantial benefits for a broad range of patients.