Prof. Antoine Lafont,
Prof. Petr Widimsky,
Presenter | see Discussant report
Petr Widimsky, FESC (Czech Republic)
List of Authors: Petr Tousek, Richard Rokyta, Jitka Tesarova, Radek Pudil, Jan Belohlavek, Josef Stasek, Filip Rohac and Petr Widimsky
Background: The outcome of acute myocardial infarction (AMI) complicated with cardiogenic shock is poor. Early mechanical revascularization is superior to medical treatment, but the mortality remains high. Registries have shown benefit from administration of GPIIb/IIIa inhibitors during primary percutaneous coronary intervention (PCI) in patients with cardiogenic shock. The aim of this study was to analyse whether upfront abciximab administration (compared with standard therapy) improves the outcomes of cardiogenic shock. Methods: This multicentre, open trial randomized 80 patients (mean age 66 years) with AMI complicated by cardiogenic shock (25% after cardiopulmonary resuscitation, 46% on mechanical ventilation) expected to undergo primary PCI into group A (routine upfront – pre-procedural - abciximab bolus followed by 12-hours abciximab infusion) and group B (standard therapy with optional abciximab administration according to the interventional cardiologist). The primary objective was 30-day combined outcome (death / reinfarction / stroke / new renal failure). Secondary objectives were: left ventricular ejection fraction assessed by echocardiography on day 30, major bleeding complications, myocardial blush grade (MBG) after PCI, TIMI-flow after PCI. Results: PCI was technically successful in 90% (A) vs. 87.5% (B) patients. Abciximab was used in 100% (A) vs. 35% (B). The primary endpoint occurred in 17 group A patients (42.5%) and 11 group B patients (27.5%, p = 0.24). Fifteen patients (37.5%) died during hospitalization in group A vs. 13 patients (32.5%) in B (p = 0.82). Ejection fraction among survivors after 30 days was 44±11% (A) vs. 41±12% (B), p = 0.205. Major bleeding occurred in 17.5% (A) vs. 7.5% (B, p = 0.310) and stroke in 2.5% (A) vs. 5% (B). No differences (A vs. B) were found in TIMI-flow and MBG after PCI. Conclusions: This study did not show any benefit from routine pre-procedural abciximab when compared with a selective abciximab use during the PCI procedure.
Discussant | see Presenter abstractAntoine Lafont, FESC (France)
Report: The Prague 7 trial is a multicenter, open, randomized study evaluating the use of Abciximab as upfront strategy with primary angioplasty in patients with acute myocardial infarction (AMI) with cardiogenic shock (CS). The primary endpoint was a 30-day combined criterion (death / reinfarction / stroke / new renal failure). The secondary endpoints were left ventricular ejection fraction assessed by echocardiography on day 30, major bleeding complications, myocardial blush grade after PCI, and TIMI-flow after PCI. The strategy facilitating primary percutaneous coronary intervention (PCI) with Abciximab in the Prague 7 study is logical since the TIMI flow appears as a major prognostic factor, influencing dramatically the mortality rate, and is greatly improved by Abciximab in several non randomized studies with CS, and randomized studies excluding CS. However, the Prague 7 trial failed to show benefit from routine pre-procedural Abciximab when compared to a selective Abciximab use during the PCI procedure. What are the reasons to explain the failure of PRAGUE 7 ? At first, authors must be acknowledged for performing a new trial in the setting of AMI with CS: indeed, inclusion of this population is a major challenge, and they were able to fulfill their goal with only 4 centers while ten years earlier, the randomized SMASH trial was stopped because of lack of recruitment of more than 55 patients involving 9 centers. The editorial entitled “Randomized trials in cardiogenic shock, what’s the problem?” in 1999, underlined the difficulties of performing randomized studies in AMI with CS. Prague 7 suffered from a lack of statistical power, and the particular difficulty of recruiting this very special population. In that matter, the study population recruited was too heterogeneous, not reflecting the standard CS population described in registries, namely an ejection fraction of 44 vs 41% one month after revascularization, which is higher than expected in this special population. The inclusion criteria were too broad. Of note, the high percentage of resuscitated patients (which were excluded in the SMASH study) represents a particular population, distinct from that of patients with CS complicating AMI. The definition of AMI was not restricted to ST+, rendering more heterogeneous the studied population: namely, the extent of ST- AMI was 20% vs 5% between the control and the study group, i.e., 80% vs 70% ST+ patients, respectively.
The randomization process (using alternate days and not a series of random numbers) does not guarantee the masking of randomization to clinician and results in imbalance between the 2 groups on some important prognostic factors: the door to balloon time, a key parameter for comparing the 2 groups, was significantly increased in the control group (60 vs 35 min, p=0.017) reflecting a bias attributable to a failure of randomization, and impairing the interpretation. The lack of power calculation led to both an arbitrary number of patients and probably a lack of statistical power. As the authors clearly recognized, the lack of results may be attributed to the small size of the population. The 35% crossover might also have participated in the lack of power of the trial. These limitations should be taken into account when analyzing the main result: no angiographic benefit attributable to Abciximab, a finding in opposition to the previous results from non randomized studies in CS that showed high procedural success rate. Not only was there no improvement in TIMI flow before PCI, but also after PCI in the study group; in ADMIRAL, CS patients with Abciximab (n=11) presented with a TIMI 3 flow in 100% vs 83.3% in the control group (n=14) 24 hours after the procedure. Even if it was not significant, this translated into a 6-month mortality rate of 9.1 vs 21.4%, and could represent a basis for power calculation. For both questionable internal validity and lack of power, these results cannot be conclusive with regards to the hypothesis. Ten years after SMASH, they remind us that evaluating therapeutic strategies in patients with CS complicating AMI is still a huge challenge for trialists.
Routine upfront abciximab versus standard peri-procedural therapy in patients undergoing primary percutaneous coronary intervention for cardiogenic shock. The PRAGUE-7 Study
This congress report accompanies a presentation given at the ESC Congress 2009. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.
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