Adenosine for Paroxysmal Supraventricular Tachycardia: Dose Ranging and Comparison with Verapamil: Assessment in Placebo-Controlled, Multicenter Trials

Abstract

OBJECTIVE: To assess the safety and efficacy of intravenous adenosine in terminating acute episodes of paroxysmal supraventricular tachycardia. DESIGN: Two prospective, double-blind, randomized, placebo-controlled trials to evaluate dose response in patients receiving adenosine and to compare the effects of adenosine with those of verapamil. PATIENTS: A total of 359 patients with a tachycardia electrocardiographically consistent with paroxysmal supraventricular tachycardia were entered into the two protocols. Patients subsequently found to have arrhythmias other than paroxysmal supraventricular tachycardia were excluded from the efficacy analysis. INTERVENTIONS: The first protocol compared sequential intravenous bolus doses of 3, 6, 9, and 12 mg of adenosine to equal volumes of saline. In the second protocol, patients received either 6 mg and, if necessary, 12 mg of adenosine or 5 mg and, if necessary, 7.5 mg of verapamil. MEASUREMENTS AND MAIN RESULTS: When data are expressed in terms of cumulative response in eligible patients, intravenous adenosine terminated acute episodes of paroxysmal supraventricular tachycardia in 35.2%, 62.3%, 80.2%, and 91.4% of patients who received maximum doses of 3, 6, 9, and 12 mg, respectively, in a four-dose sequence, whereas 8.9%, 10.7%, 14.3%, and 16.1% of patients responded to four sequential placebo doses (P less than 0.0001). In the second trial, cumulative response rates after 6 mg followed, if necessary, by 12 mg of adenosine were 57.4% and 93.4%, and after 5 mg followed, if necessary, by 7.5 mg of verapamil were 81.3% and 91.4%. The average time after injection to termination of tachycardia by adenosine was 30 seconds. Adenosine caused adverse effects in 36% of patients, but they lasted less than 1 minute and were usually mild. CONCLUSIONS: Adenosine in graded doses up to 12 mg rapidly and effectively terminates acute episodes of paroxysmal supraventricular tachycardia in which the atrioventricular node is an integral part of the re-entrant circuit. The overall efficacy of adenosine is similar to that of verapamil, but its onset of action is more rapid. Adverse reactions to adenosine are common but are minor and brief.