Curr Cardiol Rep (2014) 16:548 DOI 10.1007/s11886-014-0548-6

ECHOCARDIOGRAPHY (JM GARDIN, SECTION EDITOR)

Dual Antiplatelet Therapy in the Anticoagulated Patient Undergoing Percutaneous Coronary Intervention Risks, Benefits, and Unanswered Questions N. Bennaghmouch & W. J. M. Dewilde & J. M. Ten Berg

Published online: 19 October 2014 # Springer Science+Business Media New York 2014

Abstract A commonly encountered scenario is the patient with atrial fibrillation (AF) on oral anticoagulation (OAC) who either develops an acute coronary syndrome or has to undergo percutaneous coronary intervention with stent placement. In such patients, separate indications suggest combining OAC and dual antiplatelet therapy (DAPT). This approach, however, increases the risk of bleeding as well as thromboembolic risk if bleeding does not occur. For optimal clinical results, the risks and benefits of all possible treatment options should be determined based on the best available data. This review provides an overview of the most recent data regarding the optimal treatment of AF patients with an indication for combined treatment with OAC and DAPT. Keywords Percutaneous coronary intervention . Atrial fibrillation . Acute coronary syndrome . Triple therapy . Oral anticoagulation . Dual antiplatelet therapy

Introduction As the treated population ages, physicians increasingly are faced with treatment dilemmas due to increasing comorbidity. We frequently must combine therapies, leading to more side This article is part of the Topical Collection on Echocardiography N. Bennaghmouch (*) : J. M. Ten Berg Department of Cardiology, St Antonius Hospital Nieuwegein, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands e-mail: [email protected] J. M. Ten Berg e-mail: [email protected] W. J. M. Dewilde Department of Cardiology, Amphia Hospital Breda, Molengracht 21, 4818 CK Breda, The Netherlands e-mail: [email protected]

effects. A common dilemma is seen in patients with atrial fibrillation (AF) treated with chronic oral anticoagulation (OAC) who develop an acute coronary syndrome (ACS) or must undergo percutaneous coronary intervention (PCI) with stenting. In these patients, both OAC and dual antiplatelet therapy (DAPT) are indicated; however, this treatment combination increases the risk of bleeding. The treating physician therefore is forced to choose between a potential thromboembolic event or a bleeding complication. To prevent harm to these patients, the risks and benefits of all possible treatment options should be calculated based on robust data. This article provides an overview of the most recent available data regarding the optimal treatment of AF patients with an indication for OAC/DAPT combination therapy.

Antithrombotic Management in AF AF is a disease of the elderly population, with 45 % all AF patients aged 75 years or older. Moreover, its prevalence rises substantially with increasing age and is as high as 9.0 % in people aged 80 years or older. According to forecasts, the number of patients with AF likely will increase 2.5-folds during the next 50 years, with more than 50 % of affected individuals aged 80 years or older, reflecting the growth of the elderly population [1]. The most important consequence of AF is an increased risk of ischemic stroke, up to fivefold in patients with additional risk factors as summarized by the CHA2DS2VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65–74 years, sex category). Moreover, AF accounts for approximately 15 % of all strokes [2]. The ACTIVE-A [3], ACTIVE-W [4], and SPORTIF-III and -IV trials [5] compared different antithrombotic therapies for stroke prevention in AF. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel proved to be superior to aspirin monotherapy but inferior to

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OAC for stroke prevention [3, 4]. Adding aspirin to OAC therapy showed no benefit in preventing stroke [5]. Despite all the proven benefits of OAC, several metaanalyses have shown that OAC in AF is associated with an increased risk of major hemorrhage [6, 7]. It was found that only patients with a CHA2DS2VASc score ≥1 may be expected to derive incremental benefit from OAC, because the individual risk of stroke gradually outweighs the annual risk of major bleeding, estimated to be 1 to 2 % [8, 9]. This finding led to the development of a new generation of non-vitamin K oral anticoagulants (NOACs; e.g., dabigatran, rivaroxaban, apixaban). Compared with warfarin, the various NOACs have shown a significant reduction in stroke and systemic embolism, 18 to 23 %; mortality, 11 to 12 %; and intracranial hemorrhage, 21 to 54 % [10, 11]. The annual absolute risk of stroke or systemic embolism in these analyses has been estimated at 2.4 to 2.8 % with NOACs and 3.1 to 3.5 % with warfarin [10, 11]. Current guidelines recommend OAC as the first-choice therapy for stroke prevention in patients with AF and, based on net clinical benefit, most preferably a NOAC [10].

Antithrombotic Management in ACS and/or PCI After PCI with stent implantation, there is a risk of stent thrombosis leading to myocardial infarction (MI) as well as mortality. The incidence of stent thrombosis during the first year after stent implantation is as high as 1.2 % with a firstgeneration drug-eluting stent (DES) and 0.3 % with a secondgeneration DES [12] and is associated with a 19.2 to 27.8 % cumulative risk of death, MI, and target vessel revascularization [13]. In the early years, aspirin and OAC were given to prevent ischemic events; nevertheless, the incidence of stent thrombosis, as well as bleeding, remained high [14]. By combining aspirin and a P2Y12 inhibitor, increased inhibition of platelet activation was achieved. Compared with aspirin and OAC, DAPT resulted in a superior reduction of thrombotic events with less bleeding [14, 15]. Clopidogrel, the first P2Y12 inhibitor, has been proven to reduce the incidence of cardiovascular death, nonfatal MI, or stroke in aspirin-treated patients with ACS [16]. Despite a 38 % relative increase in major bleeding at 1 year with clopidogrel in the entire cohort, the benefit of clopidogrel treatment outweighed the bleeding risk [16]. However, because of interindividual variability in response to clopidogrel resulting in recurrence of antithrombotic complications, new P2Y12 inhibitors have emerged [17]. Compared with clopidogrel, prasugrel reduced the combined risk of cardiovascular mortality, MI, and stroke by 19 % in patients with ACS undergoing PCI (9.9 vs 12.1 %; P

Dual antiplatelet therapy in the anticoagulated patient undergoing percutaneous coronary intervention risks, benefits, and unanswered questions.

A commonly encountered scenario is the patient with atrial fibrillation (AF) on oral anticoagulation (OAC) who either develops an acute coronary syndr...
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