Thrombolysis in cardiac arrest: Initial enthusiasm tempered.

We read with great interest the comprehensive review advocating thrombolysis during cardiopulmonary resuscitation conducted by Professor Mysiak and co-workers [1]. However, we feel obliged to mention that an important contribution in this field was made last year. At the World Congress of Cardiology 2006 in Barcelona, the eagerly awaited results of the Thrombolysis in Cardiac Arrest (TROICA) trial were reported [2]. This prospective, randomized, double-blind, placebo-controlled study was set up to determine whether thrombolysis benefits in the cardiac arrest scenario extend beyond the approved indications such as ST-elevation myocardial infarction and massive pulmonary embolism. One thousand and fifty patients with a witnessed cardiac arrest of presumed cardiac origin were randomized out of hospital to receive either a weight-adjusted dose of tenecteplase or placebo after the first dose of a vasopressor. Patients were enrolled in the trial if they were at least 18 years of age and either if basic life support had been started within 10 min of onset and had been performed up to 10 min or if advanced life support had been started within 10 min of onset of cardiac arrest. The investigated drug or placebo was given by paramedics at the same time as cardiopulmonary resuscitation. The primary endpoint of the study was the 30-day survival rate, and the co-primary endpoint was hospital admission. Secondary endpoints were the return of spontaneous circulation, survival after 24 hours and survival until hospital discharge. Safety endpoints included major bleeding complications and symptomatic intracranial haemorrhage [3]. As indicated in Table 1, tenecteplase failed to improve survival in cardiac arrest patients. Nevertheless, despite the lack of difference in any of the efficacy endpoints, thrombolysis administration was safe, and no significant increase in rates of symptomatic intracranial haemorrhage or major bleeding between the two groups were observed. The negative result of the trial does not necessarily mean that thrombolysis is ineffective as an adjunctive approach to cardiopulmonary resuscitation. Contrary to the TROICA investigators, Li et al. [4], in a recent meta-analysis including 926 patients from eight studies, concluded that thrombolytic agents, when given during cardiopulmonary resuscitation, significantly improved the rate of return of spontaneous circulation, 24-hour survival, survival to discharge and longterm neurological function. Despite these facts, thrombolysis recipients were at an increased risk of severe bleeding. Similarly to the TROICA findings, in a post hoc analysis of the large randomized trial comparing vasopressin with epinephrine in out-of-hospital cardiac arrest, the use of thrombolysis did not confer any advantage in terms of hospital admission and discharge rates after adjustment for confounding variables [5]. Of note, a significantly higher crude rate of hospital admission (45.5% vs. 32.7%, p = 0.01) and a trend towards higher crude hospital discharge rate (14.1% vs. 9.5%, p = 0.14) were noticed in the thrombolysis arm. These differences may reflect the worse baseline characteristics (older age, smaller proportion of patients diagnosed with myocardial infarction or pulmonary embolism, lower occurrence