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Editor—Freemantle et al show good evidence that long term β blockade is an effective and well tolerated treatment that reduces mortality and morbidity in unselected patients after myocardial infarction.1 They present data for the end points all cause mortality and non-fatal reinfarction but make no specific reference to sudden death. They quote the results of 31 long term trials; we have been able to find data on sudden death in only 13 of these.
Sudden death is common and an important cause of death in the major long term trials after myocardial infarction. In the 13 trials that included data on sudden death the average incidence of sudden death in the placebo treated group was 51% (table). The corresponding figure in the groups treated with a β blocker was 43%. Although this suggests that β blockers do reduce the risk of sudden death, these mean figures probably grossly underestimate the potential impact of β blockers.
For interest, the table also shows results from the two largest trials, the Norwegian trial2 and the β blocker heart attack trial.3 The two drugs used in these trials, timolol and propranolol, are lipophilic non-selective β blockers and seemed to reduce the risk of sudden death. In the two recently reported β blocker heart failure studies the reduction in sudden death rates was even greater. Bisoprolol (in the cardiac insufficiency bisoprolol study II4) and metoprolol (in the metoprolol CR/XL randomised intervention trial in congestive heart failure5) decreased sudden death rates by 42% and 41% respectively.
Therefore we agree that β blockers have a key role in reducing the morbidity and mortality after myocardial infarction. There is also an important but less well recognised role for these agents in reducing the incidence of sudden death, which may account for half of the deaths in such patients.
Competing interests: Astra-Zeneca and several other drug companies that make β blockers support the department's research.
Editor—As I read through Freemantle et al's systematic review of β blockade after myocardial infarction I looked particularly for evidence about the effectiveness of atenolol.1-1 In my practice atenolol is our first choice of β blocker for hypertension, angina, and secondary prevention because it is convenient (once daily dose), cheap, and relatively free from side effects in most patients.
After the promising, if inconclusive, results of early short term trials of atenolol (pooled odds ratio 0.93; 95% confidence interval 0.85 to 1.02) it was frustrating to find that there were so few long term trials that the results (odds ratio 1.02; 0.52 to 1.99) were meaningless. The wide confidence intervals of the long term trials reflect the weight of 1.6% for long term trials of atenolol compared with 74.2% for the short term trials, and the authors rightly conclude that atenolol has been inadequately evaluated for long term use.
I and thousands of other general practitioners are thus faced with a dilemma. Should we switch patients from atenolol to propranolol (inconvenient dose or expensive sustained release preparations, plus more side effects) or timolol (also considerably more expensive than atenolol)? If we are to follow the available evidence then we should. On the other hand, absence of evidence of effectiveness is not the same as evidence of absence of effectiveness, and atenolol may, in reality, be as effective as propranolol or timolol. That we lack evidence one way or the other for the effectiveness of so ubiquitous a drug as atenolol in so important a clinical area as secondary prophylaxis of myocardial infarction represents a failure in research and development planning and policy.
Why was work on atenolol virtually abandoned after the promising early results? Was it just that newer compounds seemed more exciting than older ones? This seems unlikely, given that there is adequate evidence about propranolol, an even older drug. More probably the research agenda was driven not only by the clinical need for evidence but by the need for pharmaceutical companies to obtain evidence supportive of their products in order to increase sales. Perhaps atenolol, no longer under patent, was just too unprofitable to justify adequate research funding.
I am worried that the principles of evidence based medicine can be manipulated by pharmaceutical companies. They have the financial resources to carry out large randomised controlled trials, seeking outcomes that show their products in the most favourable light, while research on equally important questions remains underfunded.
Competing interests: None declared.