The primary end-point at 90 days was increased in the facilitated group (19% vs 13%, p = 0.0045), along with the stroke rate (1.8% vs 0%, p 0.0001). These disappointing results have been attributed, in retrospect, to an alleged pro-thrombotic effect of TBL and, more convincingly, to the risk of creating an intra-plaque hemorrhage by inﬂat- ing the balloon in the ﬁrst 2 hours after TBL (ie, in a lytic state). In retrospect, the risk of death at 90 days was reduced by TNKase facilitation when patients were randomized in ambulance (relative risk 0.74, 95% CI 0.24–2.30) and mostly increased when patients were recruited in P-PCI capable hospitals (relative risk 1.62, 95% CI 0.94–2.81). These observation raise important methodological issues about ASSENT-4 PCI, since 45% patients were actually enrolled in P-PCI capable hospital, a design not exactly germane as to deﬁne what is the best strategy for the treatment of patients at the earliest point of care, particularly in the pre-hospital setting. This holds true particularly when considering that the trial was open-label. More pertinent to investigating the role of TNKase facilitation is the WEST study,36 a randomized, open-label, feasibility study of 304 STEMI patients enrolled in the com- munity (40% enrolled pre-hospital). All patients received aspirin and ENOX and were randomized to either TNKase, or to TNKase followed by PCI within 24 hours (including rescue PCI for reperfusion failure) or to P-PCI. The time from the onset of symptoms to randomization was 113, 130 and 176 minutes respectively. There were no differences between the three groups in the primary composite of death or reinfarction, refractory ischemia, congestive heart failure, cardiogenic shock or major ventricular arrhythmia (25% vs 70 60 50 40 30 20 10 0 61 43 p = 0.02 ST-resolution (%) TNKase in acute myocardial infarction 24% vs 23%, p = NS). In the group receiving plain TNKase there was a higher rate of the death/reinfarction combination (13.0% vs 6.7% vs 4.0%, p = 0.021), but not of death (4.0% vs 1.0% vs 1.0%, p = NS). Thus, the WEST trial conﬁrms the data from CAPTIM:9 when delivered very rapidly, possibly in the pre-hospital phase, TNKase is very competitive with P-PCI and may offer a very simple and effective treatment, particularly if subsequent PCI is offered to those patients with recurrent ischemia or deemed at high clinical risk. TNKase followed by early routine PCI (within 3–12 hours, so called “pharmaco-invasive” approach) has been compared with P-PCI in 212 patients enrolled in the GRACIA-2 study.37 This is a non-inferiority trial designed to evaluate whether a lytic strategy represents a reasonable option for STEMI patients, irrespective of geographic or logistic barriers, when compared with P-PCI. The primary end-points were epicardial and myocardial reperfusion and the extent of left ventricular damage (as assessed by infarct size and left ventricular function). Complete ST-segment resolution at the electrocardiogram was observed more frequently in the TNKase group (61% vs 43%, p = 0.01), implying an improved myocardial perfusion (as measured by the TIMI myocardial perfusion grade at 60 minutes).38 Infarct size and left ventricular ejection fraction were similar in the two groups (Figure 1). It may be concluded that the results of the WEST study are conﬁrmed by GRACIA-2, suggesting the comparable efﬁcacy of TNKase (with rescue/routine PCI) and P-PCI. Most relevant to pathophysiogy and clinical practice, is the ﬁnding of GRACIA-2 (in combination with ASSENT-4 PCI) 59 56 p = NS EF (%) TNKase + routine PCI P-PCI Figure 1 ST-segment complete resolution after PCI and left ventricular ejection fraction in GRACIA-2. P-PCI = Primary angioplasty. Vascular Health and Risk Management 2009:5 253