Implications of the TIMI Trials

The TIMI Trials consist of three primary studies plus numerous ancillary observations. TIMI I was the direct reperfusion comparison between streptokinase and TPA. The central observations were: Higher reperfusion rates with TPA; Equivalent frequencies of bleeding complications; No differences in clinical outcome parameters; Only early reperfusion produced LV function improvement. TIMI IIA compared routine post-IV lytic therapy (TPA) immediate PTCA with a delayed interventional approach at 18-48 hours post lysis. The study demonstrated: Equivalent outcome LV function; Equivalent mortality rates; More emergency CABG in the "immediate" group; More hemorrhagic complications in the immediate group. TIMI IIB compared delayed but routine interventional post-lytic care (PTCA) with a more conservative strategy. Additionally patients were secondarily randomized to acute administration of IV beta blocker (metoprolol) or delayed administration of beta blocker, starting on Day 6. The primary results of this investigation include: A very low early (2 week) mortality rate with either strategy (about 5%); preserved low mortality at the one year follow up for both groups; no difference (routine intervention versus conservative strategy) in outcome LV function; no difference in comparative mortality rates; less recurrent ischemia in the routine PTCA group; 13% need for PTCA in the conservative group; no difference in LV function based upon beta blockade assignment but some decrease in mortality in acute beta blockade subgroups.