- Split View
-
Views
-
Cite
Cite
Thomas F Lüscher, Dual antiplatelet therapy: how, how long, and in which patients?, European Heart Journal, Volume 39, Issue 3, 14 January 2018, Pages 181–183, https://doi.org/10.1093/eurheartj/ehy009
- Share Icon Share
Thrombus formation is a crucial event in acute coronary syndromes,1 bypass occlusion,2 and stent thrombosis.3 In the coronary circulation, platelet activation is an initial event,4 while expression of tissue factor and subsequent activation of the coagulation cascade5 and invading white blood cells6 solidify the evolving clot, an event that often leads to vascular occlusion. Platelets are primarily activated by thromboxane and ADP via thromboxane and P2Y12 receptors on the platelet surface that eventually lead to the expression of the glycoprotein IIB/IIIA receptor that binds fibrin. Twenty-one years ago, the first randomized clinical trial established the superiority of dual antiplatelet therapy over anticoagulant therapy among patients undergoing percutaneous coronary intervention.7 Thus, dual antiplatelet therapy has become a crucial therapeutic intervention in patients with stable or acute coronary artery disease.
However, the duration of dual antiplatelet therapy and its combination with anticoagulants in certain patients remain clinical challenges. Thus, the updated ‘2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS)’, authored by Marco Valgimigli and colleagues from the European Society of Cardiology, is a timely document.8 The authors remind us that based on population estimates, ∼1.4 and 2 .2 million patients per year may have an indication for dual antiplatelet therapy after coronary intervention or a myocardial infarction, respectively. Based on >35 randomized clinical trials, including >225 000 patients, dual antiplatelet therapy is among the most intensively investigated treatments in cardiovascular medicine. Its progressive refinement involved firstly safer drugs, i.e. the move from ticlopidine to clopidogrel, and then more potent and predictable compounds such as ticagrelor or prasugrel. The need to investigate longer dual antiplatelet therapy regimens arose from concerns over late and very late stent thrombosis occurring after first-generation drug-eluting stent implantation as well as late events after an acute coronary syndrome. Yet, the advent of safer newer generation drug-eluting stents and most recent randomized trials have caused major paradigm shifts. Indeed, late and very late stent thrombosis have declined considerably with newer generation drug-eluting stents.9–11 Hence, the risk of bleeding associated with dual antiplatelet therapy prolongation beyond 1 year does not seem to be justified by the small absolute gain in preventing stent thrombosis. Yet, dual antiplatelet therapy seems to reduce the long-term risk of non-stent-related infarction and stroke.12,13 Hence, after 21 years of research, dual antiplatelet therapy has moved from a local, i.e. stent-related, to a systemic treatment strategy, i.e. capable of preventing thrombotic arterial occlusions, conveying global patient protection.
The Guidelines are complemented by ‘Case-based implementation of the 2017 ESC Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease: The Task Force for the Management of Dual Antiplatelet Therapy in Coronary Artery Disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS)’, where various cases are discussed.14
In a research article entitled ‘Clopidogrel reloading for patients with acute myocardial infarction already on clopidogrel therapy’, Jacob Doll and colleagues from the VA Puget Sound Health Care System in Seattle, Washington, USA sought to determine the association of clopidogrel reloading with in-hospital bleeding and mortality in contemporary practice (Figure 1).15 Among the 12 366 patients on pre-admission clopidogrel therapy who were admitted with ST-segment elevation myocardial infarction, 76% received a loading dose. Of 39 158 patients with non-ST-segment elevation myocardial infarction, 26% were reloaded. Reloaded patients were younger, had fewer co-morbid conditions, and were more likely to be treated with percutaneous coronary intervention. Risks of major bleeding were not significantly different between patients with and without reloading. In ST-segment elevation myocardial infarction, clopidogrel reloading was associated with a 20% lower risk of in-hospital mortality, while no mortality difference was observed in non-ST-segment elevation myocardial infarction. Thus, clopidogrel reloading is frequently practised in patients with myocardial infarction who are on pre-admission clopidogrel therapy, particularly among those with ST-segment elevation myocardial infarction. Reloading appears to be safe and may reduce in-hospital mortality in ST-segment elevation myocardial infarction.
There are limited data on optimal anti-thrombotic therapy for preventing embolism while minimizing bleeding in patients with first acute myocardial infarction complicated by a left ventricular thrombus. In their paper entitled ‘Appropriate anticoagulation combined with antiplatelet therapy was safe and effective in patients with left ventricular thrombus after first acute myocardial infarction’, Masashi Fujino and colleagues from the National Cerebral and Cardiovascular Center in Suita, Osaka in Japan further examined this issue.16 They studied 1850 patients with first acute myocardial infarction who were discharged alive. Left ventricular thrombus was diagnosed by echocardiography, left ventriculography, or cardiac magnetic resonance imaging in 5% of the patients. During a median follow-up period of 5.4 years, systemic embolism occurred in 3.6% of the 1850 patients or in 16.3% of those with left ventricular thrombus, but in only 2.9% of those without left ventricular thrombus (Figure 2). Multivariate analysis showed that left ventricular thrombus was an independent predictor of systemic embolism. Among the 84 patients with left ventricular thrombus treated with vitamin K antagonists, they compared those with a time within the therapeutic range ≥50% and those with <50%. Only one embolic event developed in those within the therapeutic range ≥50%, but nine embolic events occurred in those with <50%. There was no difference in major bleeding events. Thus, appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first acute myocardial infarction complicated by left ventricular thrombus. These clinically relevant preliminary findings in these underinvestigated patients are further discussed in an Editorial by Robert F. Storey from the University of Sheffield in the UK.17
The editors hope that this issue of the European Heart Journal will be of interest to its readers.
References
Author notes
With thanks to Amelia Meier-Batschelet for help with compilation of this article.