Myocardial infarction 6-adrenoceptor antagonists

Beta-adrenoceptor antagonists are used to treat hypertension, angina pectoris, arrhythmias and secondary myocardial infarct prevention following primary infarction (timolol, metoprolol and propranolol). 

Intermittent claudication has also been reported to be worsened by beta-adrenoceptor antagonists, but has been difficult to document because of the difficulty of study design in patients with advanced atherosclerosis. As early as 1975 it was reported from one small placebo-controlled study that propranolol did not exacerbate symptoms in patients with intermittent claudication (70). This has subsequently been supported by the results of several large placebo-controlled trials of beta-blockers in mild hypertension and reports of trials of the secondary prevention of myocardial infarction, in which intermittent claudication was not mentioned as an adverse effect, even though it was not a specific contraindication to inclusion (71). In addition, a comprehensive study of the effects of beta-adrenoceptor antagonists in patients with intermittent claudication did not show beta-blockade to be an independent risk factor for the disease (72). In men with chronic stable intermittent claudication, atenolol (50 mg bd) had no effect on walking distance or foot temperature (73). These findings have been confirmed in a recent meta-analysis of 11 randomized, controlled trials to determine whether beta-blockers exacerbate intermittent claudication (SEDA-17, 234). 

It has been argued that drug combinations that contain a beta-adrenoceptor antagonist in combination with a thiazide diuretic minimize the hypokalemic effect of the latter however, marked hypokalemia in the absence of primary hyperaldosteronism has been reported in a patient taking Sotazide (a combination of hydrochlorothiazide and the non-selective drug sotalol) (204). The use of a combination formulation of chlortaUdone and atenolol has also produced hypokalemia (205), in one case complicated by ventricular fibrillation after myocardial infarction (206). 

Interest in the possible effects of the sudden withdrawal of beta-adrenoceptor antagonists followed a 1975 report of two deaths and four life-threatening complications of coronary artery disease within 2 weeks of withdrawal of propranolol (302). Subsequent analyses did not always confirm these findings (303,304), and it has not been easy to distinguish between natural progression and deterioration caused by drug withdrawal under such circumstances. However, a case-control study in hypertensive patients showed a relative risk of 4.5 (95% Cl = 1.1, 19) associated with recent withdrawal of beta-blockers and the development of myocardial infarction or angina (305). 

After many trials including thousands of patients, it is increasingly accepted that treatment of acute myocardial infarction with beta-adrenoceptor antagonists is... 

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