FDA Panel report: January 1998.

T he Cardiovascular and Renal Advisory Panel of the FDA met January 27-28, 1998, to discuss (1) evaluation and use of intravenous inotropic agents in patients with heart failure; (2) liver function test abnormalities with a new AT 1 receptor blocker, tasosartan; and (3) the use of the platelet IIb/IIIa receptor blocker eptifibatide in syndromes of acute cardiac ischemia. Intravenous drugs for the treatment of heart failure historically have been approved after demonstration of acute dose-dependent hemodynamic effects in patients with heart failure. Recently, however, there appears to have been a marked increase in the intermittent or continuous use of intravenous inotropic agents for longer periods than originally anticipated, often without monitoring of cardiac rhythm. This practice has become prevalent despite recent trials with oral inotropic agents that have shown adverse effects on mortality and morbidity during long-term treatment and preclinical data presented to the committee that raised the possibility that intermittent exposure to intravenously administered positive inotropic agents may accelerate myocardial cell death. The committee therefore voted unanimously that short-term use of intravenous inotropic agents for decompensated heart failure should be approved if an improvement in symptoms, renal function, and/or hemodynamics (including patients after bypass surgery) can be shown. However, for prolonged intermittent or continuous intravenous use, an improvement in survival and symptoms should be demonstrated in a placebo-controlled trial. The committee unanimously recommended that labeling of intravenous positive inotropic agents be revised to reflect the following: (1) that these drugs are indicated for patients who are hospitalized with acutely decompensated heart failure, (2) that there is no experience in controlled trials with continuous infusions for periods Ͼ24 to 48 hours, (3) that there is no evidence that these drugs are effective or safe in patients with heart failure if used intermittently or continuously as a short-term or long-term management strategy, (4) that long-term oral use of these drugs has been associated with an increased risk of hospitalization and death, and (5) that there is no evidence that long-term use of these drugs given intravenously does not carry a similar risk. Tasosartan is an AT 1 receptor blocker with a slowly eliminated active metabolite. Its antihypertensive efficacy seems to be similar to that of irbesartan, losartan, and valsartan. In the tasosartan database, however, values of AST or ALT twice the upper limit of normal were seen in 16 of 950 patients (1.7% versus 1.2% in placebo) and 8 times …