Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease

Abstract

SummaryUntil recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

Development of New Antithrombotic Regimens for Patients with Acute Coronary Syndrome

“…The development of NOACs, which have demonstrated fewer intracranial bleeding events and deaths than VKAs in AF trials [ 32 ], has renewed interest in a dual pathway strategy for the secondary prevention of ACS, targeting both the coagulation cascade and the platelet component of thrombus formation [ 7 , 33 ].…”

“…In addition, compared with ATLAS ACS 2 TIMI 51, APPRAISE-2 patients were older and more likely to have diabetes mellitus and/or renal dysfunction, and non-ST-elevation MI versus ST-elevation MI as their index event [ 19 , 22 , 33 ]. Furthermore, ATLAS ACS 2 TIMI 51 excluded patients with prior stroke or transient ischemic attack who were already receiving ASA plus a P2Y 12 inhibitor [ 22 , 33 ]. The higher-risk population of APPRAISE-2 may have been less responsive to anticoagulant therapy than the ATLAS ACS 2 TIMI 51 population [ 22 , 33 ].…”

Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation

“…With the limitation of a relatively short follow-up period, no difference between groups for bleeding events was observed [ 106 ]. Another hot topic in NOAC therapy is co-medication with antiplatelet drugs (triple therapy) due to coronary artery disease and consecutive interventions and has been discussed in detail elsewhere [ 107 ]. In addition, special situations, e.g., new-onset atrial fibrillation post cardiac surgery and anticoagulation during cardioversion or catheter ablation, are currently extensively studied [ 108 – 110 ].…”

Oral Anticoagulants and Renal Impairment: The Convoluting Dilemma

“…The optimal utilization of oral anticoagulants (OAC) in patients with renal impairment (RI) represents an urgent, unmet, and yet unsolved need with regard to the choice of agents, duration of treatment, and potential dose/regimen adjustment ( De Caterina et al, 2016 , Verheugt and Granger, 2015 ). Lack of any large randomized trials adequately designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the government agencies, and endless overoptimistic publications based on post hoc analyses of primary mega trials sometimes exaggerating benefits and hiding risks cloud the reality.…”

“…Our inability to assess adequately the impact of OA on long-term outcomes in these patients has been well recognized e.g. ( De Caterina et al, 2016 , Verheugt and Granger, 2015 , Blann and Lip, 2015 , Ng et al, 2013 ).…”