Atenolol infarction

First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction ISIS-1. Lancet 1986 2(8498) 57-66. 

Finally, the toxicity of some effective drugs prevents their use at maximally effective dosage. The widespread indiscriminate use of 3 blockers has been criticized because several large clinical trials indicate that some members of the group, eg, metoprolol and carvedilol, have a greater benefit than others, eg, atenolol. However, all 3 blockers appear to have similar benefits in reducing mortality after myocardial infarction, so these drugs are particularly indicated in patients with an infarct and hypertension. 

Propranolol was the first blocker shown to be effective in hypertension and ischemic heart disease. Propranolol has now been largely replaced by cardioselective blockers such as metoprolol and atenolol. All B-adrenoceptor-blocking agents are useful for lowering blood pressure in mild to moderate hypertension. In severe hypertension, blockers are especially useful in preventing the reflex tachycardia that often results from treatment with direct vasodilators. Beta blockers have been shown to reduce mortality after a myocardial infarction and some also reduce mortality in patients with heart failure they are particularly advantageous for treating hypertension in patients with these conditions (see Chapter 13). 

Atenolol [Tenormin). Like acebutolol, atenolol is regarded as beta-1 selective, but tends to be less beta-specific at higher doses. The drug is administered orally for the long-term treatment of hypertension and chronic, stable angina. Atenolol is also administered immediately following a myocardial infarction to prevent reinfarction and to promote recovery of the myocardium. 

Metoprolol, atenolol, and several other drugs (see Table 10-2) are members of the Di-selective group. These agents may be safer in patients who experience bronchoconstriction in response to propranolol. Since their Bi selectivity is rather modest, they should be used with great caution, if at all, in patients with a history of asthma. However, in selected patients with chronic obstructive lung disease the benefits may exceed the risks, eg, in patients with myocardial infarction. Betai-selective antagonists may be preferable in patients with diabetes or peripheral vascular disease when therapy with a 6-blocker is required since B2 receptors are probably important in liver (recovery from hypoglycemia) and blood vessels (vasodilation). 

Beta (/3)-blockers (e.g., propranolol, atenolol, oxyprenolol, pindolol) are used for treating hypertension, cardiac arrhythmias, angina pectoris, and myocardial infarction. These drugs have proven important in the management of alcohol withdrawal and hypothyroidism.56 -blockers also are used as prophylactics in... 

The major clinical uses of atenolol include hypertension angina pectoris acute myocardial infarction (MI) heart rhythm disturbances and migraine prophylaxis. In hypertonia disease, various studies have addressed the efficacy of atenolol in... 

In acute MI, the ISIS-1 study [88] was organized to assess the effects of early beta-blockade with atenolol on cardiovascular mortality during the first week following infarction and after long-term (mean 20 months) follow-up. There was a 15% reduction in vascular deaths, especially in the early phase of MI. The difference in early mortality was mainly due to a reduction in electromechanical dissociation in the presence of atenolol. In this regard, atenolol is usually given by intravenous injection or infusion to treat cardiac arrhythmias, and it should be noted that atenolol induced atrial fibrillation in half of the so-predisposed patients [89]. 

There is strong evidence that beta-blockers can reduce mortality by up to 23% post myocardial infarction. Beta-blockers should be used to reduce the risk of further cardiovascular disease events irrespective of whether the blood pressure is raised or not. There is no evidence that any beta-blocker is more effective than another in secondary prevention, hence a beta-blocker which is well tolerated and that can be taken once or twice daily should be used. Atenolol, bisoprolol or metoprolol are suitable agents. These agents are not specifically licensed post myocardial infarction but all are licensed for angina and the doses for this indication should be used i.e. 

Figure 10.12. p-Receptorblockers. a Stractures of propranolol (not subtype-selective) and of atenolol (P2-selective). b Effect of propranolol and of atenolol on the survival rate of patients after myocardial infarction Data from American Journal of Cardiology, 87 823-826 (2001)... 

Page 95, figure 10.12 Redrawn after American Journal of Cardiology 87 823-826 (2001), Gottlieb S.S. et al. Comparative effects of three beta blockers (atenolol, metopro-lol, and propranolol) on survival after acute myocardial infarction. Reproduced with permission from Excerpta Medina Inc. 

Early use within 6 hours (or at most 12 h) of onset (i.v. for 24 h then oral for 3-4 weeks). Benefit has been demonstrated only for atenolol. Cardiac work is reduced, resulting in a reduction in infarct size by up to 25% and protection against cardiac rupture. 

A randomized comparison of oral atenolol and bisoprolol in 334 patients with acute myocardial infarction was associated with drug withdrawal in 70 patients (21%) because of significant bradydysrhythmias, hypotension, heart failure, and abnormal atrioventricular conduction (40). Logistic regression analysis suggested that critical events were more likely to occur in patients who were pretreated with dihydropyridine calcium antagonists. 

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). 

Van De Ven LLM, Spanjaard JN, De Jongste MIL, Hillege H, Verkenne P, Van Gilst WH, Lie KI. Safety of beta-blocker therapy with and without thrombolysis A comparison or bisoprolol and atenolol in acute myocardial infarction. Curr Ther Res Clin Exp 1996 57 313. 

Rossi PR, Yusuf S, Ramsdale D, Furze L, Sleight P. Reduction of ventricular arrhythmias by early intravenous atenolol in suspected acute myocardial infarction. BMJ (Clin Res Ed) 1983 286(6364) 506-10. 

A 38-year-old white man with a history of coronary artery disease, myocardial infarction, coronary artery by-pass, alcoholism, and depression took a combined massive overdose of diltiazem and atenolol (24). He underwent cardiopulmonary resuscitation because of cardiac arrest bradycardia, hypotension, and oliguria followed and were resistant to intravenous pacing and multiple pharmacological interventions, including intravenous fluids, calcium, dopamine, dobutamine, adrenaline, prenalterol, and glucagon. Adequate mean arterial pressure and urine output were restored only after the addition of phenylephrine and transvenous pacing. He survived despite myocardial infarction and pneumonia. 

The Losartan Intevention Eor Endpoint (LIFE) trial was a prospective study that compared losartan versus atenolol in patients with LVH and hypertension. Losartan was more effective than atenolol in reducing the combined end point of stroke, myocardial infarction, and death. When patients with diabetes from the LIFE trial were evaluated is a subanalysis, there was a significant reduction in both cardiovascular morbidity and mortahty with losartan versus atenolol. Despite this evidence, LVH is not considered a compelling indication for ARBs in the INC7. 

Landmark clinical trials have established the role of early fi-blocker therapy in reducing MI mortality. Most of these trials were performed in the 1970s and 1980s before routine use of early reperfusion therapy. In the First International Study of Infarct Survival (ISIS-1), 16,027 patients with a suspected MI were randomized to IV atenolol 5 to 10 mg followed by atenolol 100 mg daily for 7 days or to no treatment. After 7 days, vascular death was reduced by 15% p <.04). Thebenefltwas apparent after 1 day of treatment(p <. 003), reflecting the ability of /S-blockers to prevent early reinfarction and sudden death. In the Metoprolol In Acute Myocardial Infarction (MIAMI) trial, 5778 patients with a suspected MI were randomized to IV metoprolol followed by oral metoprolol or placebo, and mortality was reduced from 4.9% to 4.3% (p = NS), and the occurrence of early progression to Q-wave MI also was reduced (p =. 024). ... 

Atenolol is indicated in arteriosclerotic heart disease with angina pectoris, hypertension, cardiac arrhythmias and myocardial infarction in hypertrophic obstructive cardiomyopathy, dissecting aneurysm of the aorta, pheochro-mocytoma, and in prevention of migraine headaches. 

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