VALIDATE-SWEDEHEART, TROPICAL-ACS and RE-DUAL PCI: Antithrombotic Therapy takes the stage
Reported from the European Society of Cardiology ESC Congress 2017 in Barcelona
In the accompanying editorial of COMPASS, presented at the ESC Congress 2017 in Barcelona, Eugene Braunwald vividly referred to the field of “Thrombocardiology”. Indeed, the topic of antithrombotic pharmacotherapy is now broader than ever, with plenty of drugs, indications, strategies and clinical data. Three new trials (with simultaneous publications in the New England Journal of Medicine and in The Lancet) clarify doubts, inform clinical practice and open new questions.
VALIDATE-SWEDEHEART: Bye Bye Bivalirudin?
One may wonder why we needed a new trial of bivalirudin versus heparin after HORIZON-AMI, EUROMAX, HEAT-PPCI, MATRIX and so on. The VALIDATE-SWEDEHEART trial is probably the most contemporary of all these studies, eliminating a number of confounding factors: all patients presented STEMI or NSTEMI and were on prasugrel or ticagrelor, glycoprotein IIb/IIIa inhibitors were not routinely used, radial access was mostly adopted for PCI. In this context, after controversial findings from previous trials, this looked like the ultimate chance for bivalirudin to display its superiority, if any. Nevertheless, we are now aware that this did not happen at 6-month follow-up in 6,006 randomized patients with respect to a composite of death, myocardial infarction or major bleeding. There were neither differences in major bleeding nor in stent thrombosis, solidifying the idea that the old, good and cheap heparin is enough for the purposes of anticoagulation for PCI patients with myocardial infarction.
TROPICAL-ACS: More substance to the de-escalation hypothesis
Earlier this year at EuroPCR, the TOPIC trial raised the issue that de-escalation from prasugrel or ticagrelor to clopidogrel after one month in patients with ACS is superior to the traditional DAPT strategy in preventing bleeding complications. TOPIC was a small yet provocative randomized trial of 646 patients, so there was no ambition to investigate whether the step-down antiplatelet strategy is also equally protective beyond its safety promise. The TROPICAL-ACS investigators bring the de-escalation hypothesis to a new level and adds now their voice to the debate with a well-performed randomized study of 2,610 patients, published in the Lancet.
The hypothesis tested by TROPICAL-ACS is that platelet function testing while on clopidogrel at 2 weeks (with the first 7 days actually on prasugrel, followed by switch) meaningfully discriminate ACS patients who can safely continue on clopidogrel and those that achieve better outcomes with prasugrel (a truly tailored approach). This strategy proved noninferior to the traditional strategy of 1-year DAPT with prasugrel with respect to the composite of cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to BARC criteria, and appeared to show noninferior protection with respect to the composite of ischemic events, this latter being a question better addressed by larger studies powered for efficacy. While this study does not confute the current guideline-recommended approach, de-escalation guided by platelet function testing could be now be considered a safe alternative for, i.e., selected ACS patients at high bleeding risk with adequate platelet inhibition while on clopidogrel.
RE-DUAL PCI: Another argument against triple antithrombotic therapy
To protect atrial fibrillation patients undergoing PCI from the risk of thromboembolic and coronary complications, we need to use both anticoagulant and antiplatelet drugs because the principle behind the formation of a thrombus in the atrium or inside a stent implies different mechanisms and pathways. Dual therapy (i.e., an oral anticoagulant plus an antiplatelet drug) reduced bleeding compared with triple therapy (i.e., an oral anticoagulant plus DAPT) in WOEST and PIONEER-AF.
RE-DUAL PCI, now published in the New England Journal of Medicine, randomly assigned 2,725 patients with atrial fibrillation and PCI to triple therapy or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus clopidogrel or ticagrelor and no aspirin.Once again, the risk of major or clinically relevant nonmajor bleeding was lower among patients who received dual therapy than among those who received triple therapy, meeting the objectives of noninferiority and superiority. In addition, dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. This trial reinforces current understanding that, in the era of NOACs, dual therapy is a viable option in patients with atrial fibrillation who receive coronary stents.