s' reply [5]

Indications:Patients with myocardial infarction.Patients:-TypeofStudy:Letters to the editor.DosageDuration:-Results:-AdverseEffects:Unspecified number of patients developed cardiogenic shock.FreeText:Authors reply on the comments with reference to the use of clopidogrel and Lopresor in myocardial infarction. The authors stated that the patients in Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) were eligible only if their physicians were uncertain as to whether the treatment was clearly indicated or clearly contraindicated. This approach, the authors said, has the practical advantage of excluding all patients in whom there were considered to be clear contraindications to the study treatment, while still allowing the balance of benefits and risks to be assessed in a wide range of settings where uncertainty persisted. The authors proceeded stating that overall, the control incidence of cardiogenic shock after randomization was only about 4% in COMMIT, chiefly because patients at high risk of developing shock were generally excluded by their doctors. The intravenous then oral Lopresor regimen was carefully titrated, and doctors were free to alter the treatment as required for each particular patient. Although a small pharmacodynamic study indicated that Chinese individuals may require lower beta-blocker doses, titration of the iv Lopresor in COMMIT resulted in doses very similar to those given in the previous MIAMI trial among Caucasians. For example, all three intravenous Lopresor injections were received by 94% of COMMIT patients in the low-risk subset defined to correspond to the MIAMI entry criteria (Killip I, systolic blood pressure > 105 mm Hg and heart rate >65 bpm) compared with 95% among such patients in MIAMI. Compliance with the oral Lopresor regimen in COMMIT was also about the same as with the similar oral regimen in MIAMI. But despite the care with which patients were selected and treatment was used in COMMIT, allocation to Lopresor produced a highly significant increase in the incidence of cardiogenic shock, and the proportional increase was similar (about 30%) across many different types of patient studied, including those presenting without heart failure or hypotension. The authors continued stating that the COMMIT results indicate that the hazards of immediate bet-blocker therapy after acute myocardial infarction outweigh the benefits in patients at high risk of developing shock. So, a policy of delaying the initiation of beta-blocker therapy until patients are hemodynamically stable may well avoid much of the benefit. Lastly the authors stated that no specific information was recorded in COMMIT about the risks of gastrointestinal bleeding, although patients with a recent history of gastric ulcer were generally excluded, especially if fibrinolytic therapy was to be given. There was, however, no evidence that the addition of clopidogrel to aspirin for an average of about 2 weeks after acute myocardial infarction produced any material increase in the incidence of any particular type of serious bleed. Even so, it may well be worth considering the addition of a proton pump inhibitor to prevent gastrointestinal bleeding in patients who are to receive prolonged antiplatelet therapy for the prevention of heart attacks and strokes.