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Aims Cardiogenic shock (CGS) occurs in 6-10% of patients with acute coronary syndromes (ACS). Mortality has fallen over time from 80% to approximately 50% consequent on acute revascularisation but has plateaued since the 1990s. Once established, patients with CGS develop adverse compensatory mechanisms that contribute to the downward spiral towards death, which becomes difficult to reverse. We aimed to test in a robust, prospective, randomised controlled trial whether early support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides clinical benefit by improving mortality and morbidity. Methods and results The EURO SHOCK trial will test the benefit or otherwise of mechanical cardiac support using VA-ECMO, initiated early after acute percutaneous coronary intervention (PCI) for CGS. The trial sets out to randomise 428 patients with CGS complicating ACS, following primary PCI (P-PCI), to either very early ECMO plus standard pharmacotherapy, or standard pharmacotherapy alone. It will be conducted in 39 European centres. The primary endpoint is 30-day all-cause mortality with key secondary endpoints: 1) 12-month all-cause mortality or admission for heart failure, 2) 12-month all-cause mortality, 3) 12-month admission for heart failure. Cost-effectiveness analysis (including quality of life measures) will be embedded. Mechanistic and hypothesis-generating substudies will be undertaken. Conclusions The EURO SHOCK trial will determine whether early initiation of VA-ECMO in patients presenting with ACS-CGS persisting after PCI improves mortality and morbidity.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

Cerebral infarction is the most serious complication of atrial fibrillation. Coumarin derivatives (vitamin K antagonists) counteract systemic thromboembolism and reduce the risk of stroke by more than 60%, but carry a risk of serious bleeding. Antiplatelet therapy and subcutaneous low-molecular-weight heparin are as yet not sufficiently effective and are associated with a bleeding risk similar to vitamin K antagonists. Vitamin K antagonists require intensive INR monitoring to ensure efficacy and safety. In the past decade, oral agents have been developed that directly inhibit the activity of thrombin (factor IIa) and of activated factor X (Xa), which is the first compound in the final common pathway of the coagulation cascade. These do require INR monitoring and have rapid onset and offset of action. The first results with thrombin blockers, such as dabigatran, look promising in efficacy and safety and Xa inhibitors are currently under investigation in atrial fibrillation in 3 large clinical trials. Long-term safety of the new agents in patients with atrial fibrillation has not yet been determined.

The investigators undertook a systematic, comprehensive analysis of the therapeutic response and clinical outcomes of reperfusion therapy for acute ST-segment elevation myocardial infarction (STEMI) in 5,470 patients from the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 trial.Prompt effective reperfusion therapy for acute STEMI may attenuate major myocardial necrosis.We prospectively collected sequential electrocardiographs and clinical data. Aborted myocardial infarction (MI) was defined as maximal creatine kinaseor =2x upper limit of normal coupled with typical evolutionary electrocardiographic changes.Of the patients, 727 (13.3%) had an aborted MI, with the highest frequency (25%) occurring in patients treated1 h after symptom onset. As compared with MI patients, patients with aborted MI more often had complete ST-segment resolution at 60 min (56.3% vs. 30.2%, p0.001) and 180 min (61.5% vs. 53%, p0.001); they also had smaller infarct sizes based on QRS score at discharge (2.37 vs. 4.62, p0.001). Mortality in aborted MI patients compared with those who had true MI was 3.9% versus 4.6% at 30-day and 7.0% versus 7.4% at 1-year. The baseline-adjusted mortality was significantly lower in patients with aborted MI (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63 to 0.92, p = 0.005 for 30-day and OR 0.70, 95% CI 0.50 to 0.98, p = 0.035 for one year). A very low-risk subset was identified withor =70% ST-segment resolution at 60 min whose 30-day and 1-year mortality was 1.0% and 2.7%, respectively, compared with 5.9% and 9.3% in aborted MI patients with70% ST-segment resolution at 60 min (all por = 0.002).Prompt fibrinolytic treatment improved the likelihood of aborted MI. The subgroup with complete 60-min ST-segment resolution had the best clinical outcomes.