The VIAMI-trial is the first RCT investigating a viability-guided invasive approach in patients who were at least 48 hours stable after acute MI (not treated with primary PCI), demonstrating that only patients with viable tissue in the infarct-area showed benefit from an early in-hospital culprit vessel revascularization.
Viability was used as a sensitive marker of risk of recurrent ischemia and recurrent infarction, with the notion that recurrent ischemic events in the post-MI period in most instances is related to re-thrombosis in the infarct-related coronary artery, combined with residual viable tissue in the infarct-area.
Several studies evaluated early invasive intervention after thrombolysis [19
]. The only trials studying the effect of a routine invasive strategy after fibrinolysis beyond the time window of expected myocardial salvage were the GRACIA-1 and OAT. The TRANSFER-AMI and NORDISTEMI trials investigated this only in part. In the GRACIA-1 trial a routine invasive strategy within 24 hours (mean 19.6 hours) of thrombolysis in the modern era of PCI was investigated, compared with ischemia-guided conservative approach [25
]. During the index hospital stay, no significant difference in hard endpoints (death or reinfarction) between the conservative and invasive treated group was demonstrated. Only the revascularization procedures differed significantly. At 1 year follow-up, a significant reduction of ischemia-related readmission to hospital and revascularization was observed without significant differences in non-fatal reinfarction or death. Both open and occluded arteries were included. The OAT trial included only patients with occluded arteries 3 to 28 days after AMI. Therefore, the OAT trial is the only trial addressing the routine opening of an occluded artery beyond the time window of expected myocardial salvage. The 4 year cumulative primary event rate (death, reinfarction or heart failure) did not differ significantly (17.2% PCI group vs. 15.6% medical group), with a trend toward excess reinfarction (p = 0.08) [26
]. The TRANSFER-AMI trial compared high risk AMI patients treated with fibrinolysis and early PCI (< 6 hours) or fibrinolysis and standard-treatment. Overall, 88,7% of the patients in the standard group underwent coronary angiography after a mean of 32.5 hours. Urgent or rescue catheterization was performed within 12 hours after fibrinolysis in 34.9% of patients. After 6 months, no significant differences in incidence of death or reinfarction were demonstrated between the routine early PCI and standard treatment (p = 0.36) [20
]. The same strategy was investigated in the NORDISTEMI trial. The standard treatment group underwent PCI 3 days (median) after AMI. Overall, in 95% of this group angiography was performed at a mean of 5.5 days. Urgent or rescue procedures within 12 hours were performed in 33%. No significant difference in primary endpoint was found after 1 year follow up (composite death, reinfarction, stroke, or new myocardial ischemia). Only composite of death, reinfarction and stroke differed significantly (p = 0.01) [24
]. Comparing these trials with the VIAMI-trial is difficult, since we included only stable patients after AMI, representing a selected group of more or less low to intermediate risk. In the VIAMI trial no urgent or rescue PCI was performed as these patients were not included in the trial. In the conservative, non-invasive group of the VIAMI trial routine angiography was not recommended. Angiography was only performed in case of recurrent ischemia or proven ischemia with stress-testing. Overall, in the conservative group 41% (45/110) of patients underwent coronary angiography.
With regard to the recommended treatment post-thrombolysis, the AHA/ACC and ESC guidelines differ diminutively. The AHA/ACC guidelines recommend an early pharmacoinvasive strategy after thrombolysis in high risk patients (Class IIa, level B). In non-high risk patients such a strategy could be considered, especially if ischemic symptoms persist and failure to reperfuse is suspected (Class IIb, level C). The ESC guidelines and ESC guidelines for PCI recommend a routine invasive strategy within 24 hours after successful thrombolysis if available (Class IIa, level A). In stable patients who did not receive reperfusion therapy, angiography could be considered before discharge (Class IIb, level C) [1
]. However, only the GRACIA-1 trial investigated a routine invasive strategy beyond the time window of expected myocardial salvage and demonstrated a reduction in endpoints (death, re-infarction and ischemia driven revascularization) after 12 months. In our opinion, insufficient for the generalized statement that routine intervention is warranted in patients after successful thrombolysis as recommended by the ESC guidelines.
As an unexpected finding, patients without viability underwent as many revascularization procedures as patients with viability who were randomized to the conservative strategy. Although patients without viability had a low recurrence-rate of acute coronary syndrome, they had similar reported CCS-class of angina compared to the viable-conservative patients. Despite a lower rate of spontaneous ischemic events and less proven ischemia during stress-testing, treating physicians decided to refer patients for an invasive procedure quite as often in the non-viable patient group. The explanation for this remains speculative.
The results of the VIAMI trial suggest that routine angioplasty in the early post-MI period in stable patients (whether or not treated with thrombolysis) is not mandatory. Especially in patients were the transport time for primary PCI is largely exceeding 90 minutes as recommended by the AHA/ACC guidelines, thrombolysis could be an interesting alternative with the VIAMI-trial approach. Also in patients presenting too late for reperfusion therapy (> 12 hours). Early viability-testing with low-dose dobutamine echocardiography provides us with a tool to identify high-risk patients who will have clinical benefit from a revascularization procedure later on.
The applicability of LDDE in daily practice is somewhat limited because about 10-15% of patients have poor acoustic windows. In our study this problem could partially be overcome with selective use of ultrasound contrast agents.
The pre-specified number of patients was not achieved. This was mainly caused by a slowing down of inclusion-rate in the second half of the study period due to the fast introduction of widely available primary PCI in the Netherlands. Although the primary event-rate in the viable-conservative group was lower than expected (17.3%) the relative risk-reduction was higher than expected (56.6%). This indicates an improvement over time in the pharmacological post-MI treatment (statins, clopidogrel, ACE-inhibitors). Also, it implicates further improvement in the efficacy and safety-profile of revascularization procedures. During the inclusion-period of the VIAMI-trial treatment with clopidogrel was not standard care in patients without stents. Standard treatment with clopidogrel according to current guidelines (CLARITY-TIMI 28 trial [28
]) could have made the differences less pronounced.
The data from the non-viable patient group should be interpreted with caution, because this was a non-randomized group.
Half of the randomized patients were not treated with thrombolysis, making it a heterogeneous group. The outcome in these two seemingly different patient groups, however, was exactly the same. This finding challenges the general idea that patients with ST-segment elevation MI not treated with thrombolysis have completely different residual culprit vessel pathology with different early and long term clinical outcome than patients who were treated with thrombolysis. The VIAMI-trial supports the concept that, ultimately, it is viability that determines prognosis.