Journal of Clinical Medicine Viewpoint Optimal Antithrombotic Treatment of Patients with Atrial Fibrillation Early after an Acute Coronary Syndrome—Triple Therapy, Dual Antithrombotic Therapy with an Anticoagulant ::: Or, Rather, Temporary Dual Antiplatelet Therapy? Ugo Limbruno 1, Francesco De Sensi 1, Alberto Cresti 1, Andrea Picchi 1, Fabio Lena 2 and Raffaele De Caterina 3,4,* 1 Cardioneurovascular Department, Azienda USL Toscana Sudest, 58100 Grosseto, Italy; [email protected] (U.L.); [email protected] (F.D.S.); [email protected] (A.C.); [email protected] (A.P.) 2 Pharmacy Department, Azienda USL Toscana Sudest, 58100 Grosseto, Italy; [email protected] 3 Cardio-Thoracic and Vascular Department, Pisa University Hospital and University of Pisa, 56124 Pisa, Italy 4 Fondazione VillaSerena per la Ricerca, Città Sant’Angelo, 65013 Pescara, Italy * Correspondence: raff[email protected]; Tel.: +39-050-996-751 Received: 9 July 2020; Accepted: 12 August 2020; Published: 18 August 2020 Abstract: The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y12 inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y12 inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF–ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA2DS2VASc score 2–4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial. Keywords: acute coronary syndrome; atrial fibrillation; oral anticoagulant therapy; antithrombotic therapy; P2Y12 inhibition; tailored therapy 1. Introduction The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) poses complex therapeutic dilemmas. Here, cardiologists face a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—which must be carefully managed and with important threats. Triple antithrombotic combination therapy (TAT), i.e., oral anticoagulation (OAC) on top of dual antiplatelet therapy (DAPT), has been for two decades the milestone for treatment of these patients. Due to the high and sometimes prohibitive hemorrhagic burden of TAT, several dual antithrombotic therapy (DAT) J. Clin. Med. 2020, 9, 2673; doi:10.3390/jcm9082673 www.mdpi.com/journal/jcm J. Clin. Med. 2020, 9, x FOR PEER REVIEW 2 of 11 antithromboticJ. Clin. Med. 2020, 9 , 2673combination therapy (TAT), i.e., oral anticoagulation (OAC) on top of 2dual of 11 antiplatelet therapy (DAPT), has been for two decades the milestone for treatment of these patients. Due to the high and sometimes prohibitive hemorrhagic burden of TAT, several dual antithromboticregimens, i.e., OAC therapy plus (DAT) a single regimens, antiplatelet i.e., agent, OAC have plus been a single proposed antiplatelet in randomized agent, have trials [been1–5] withproposed the aim in random of improvingized trials safety [1–5] without with the hampering aim of improving efficacy. Current safety without guidelines hampering [1,2] endorse efficacy. this Currentapproach guidelines in patients [1,2] at high endorse bleeding this approach risk. In such in patients a condition, at high OAC bleeding has, however, risk. In such always a condition, remained OACan undisputed has, however, cornerstone. always remained an undisputed cornerstone. We here describe the rather frequent scenario of a patient admitted to our hospital, in order to argue against such a mantra, advocating the possibility of temporarily omitting anticoagulation in some circumstances. 2. Case Case Vignette Vignette A 7373 year-oldyear-old male male with with a historya history of hypertensionof hypertension and AFand in AF treatment in treatment with rivaroxaban with rivaroxaban 20 mg/day 20 wasmg/day admitted was admitted to our hospital to our hospital for a non-ST for a non- segmentST segment elevation elevation ACS. The ACS. electrocardiogram The electrocardiogram (ECG) (ECG)on admission on admission showed AFshowed and ST-segmentAF and ST-segment depression depression in the inferior in leads.the inferior Coronary leads. angiography Coronary angiographyrevealed a tight revealed stenosis a in tight the right stenosis coronary in the artery right and coronary a long 75% artery maximum and a diameter long 75% stenosis maximum in the proximaldiameter stenosis and mid-left in the anterior proximal descending and mid-left coronary anterior artery descending (Figure1 ).coronary artery (Figure 1). Figure 1.1. CoronaryCoronary angiography angiography in thein the patient patient case ca describedse described in the in case the vignette. case vignette. (A) The right(A) The coronary right coronaryartery shows artery a tightshows stenosis a tight in stenosis the mid in segment the mid (culprit segment lesion). (culprit (B) lesion). The left ( anteriorB) The left descending anterior descendingcoronary artery coronary shows artery a long show 75%s maximum a long 75% diameter maximum stenosis diameter in the stenosis proximal in the and proximal mid segments. and mid segments. His CHA2DS2VASc score was 3 (age 65–74, hypertension, vascular disease). Because of this, OACHis was CHA considered2DS2VASc necessary. score was The 3 patient(age 65–74, received hypertension, percutaneous vascular coronary disease). intervention Because (PCI)of this, of OACthe right was coronary considered artery, necessary. considered The patient the culprit received vessel, percutaneous with a Xience coronary Prime (2.75intervention28 mm) (PCI) stent of × (Figurethe right2A). coronary Threedays artery, later, considered the proximal the culprit and mid vessel, left anterior with a descendingXience Prime coronary (2.75 × artery28 mm) lesions stent were(Figure treated 2A). Three with thedays implantation later, the proximal of three and Xience mid Prime left anterior (3.0 38descending mm, 3.0 coronary15 mm, 2.75artery 15lesions mm) × × × werestents treated (Figure with2B). the implantation of three Xience Prime (3.0 × 38 mm, 3.0 × 15 mm, 2.75 × 15 mm) stentsAfter (Figure the 2B). procedure, TAT with aspirin, clopidogrel, and rivaroxaban 15 mg/day was prescribed. However, because of the patient’s high bleeding risk (HAS-BLED) score (hypertension, age, abnormal renal function, need for antiplatelet therapy = 4), and because blood tests on day four showed a drop of hemoglobin from an initial value of 12.0 to 8.5 g/dL, aspirin was discontinued on day six, and the patient was discharged on a combination of rivaroxaban 15 mg/day and clopidogrel 75 mg/day. Two weeks after the hospital discharge, the patient was readmitted to the emergency department, this time with an anterior ST-segment elevation myocardial infarction. Coronary angiography showed a subacute stent thrombosis of the left anterior descending coronary artery (Figure3), which was effectively treated with mechanical thrombus aspiration and balloon dilatation. J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 11 J. Clin. Med. 2020, 9, 2673 3 of 11 J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 11 Figure 2. Percutaneous coronary intervention in the patient case described in the case vignette. (A) The right coronary artery lesion was treated with the implant of a Xience Prime (2.75 × 28 mm) stent. (B) The proximal and mid left anterior descending coronary artery lesions were treated with the implantation of three Xience Prime (3.0 × 38 mm, 3.0 × 15 mm, 2.75 × 15 mm) stents. After the procedure, TAT with aspirin, clopidogrel, and rivaroxaban 15 mg/day was prescribed. However, because of the patient’s high bleeding risk (HAS-BLED) score (hypertension, age, abnormal renal function, need for antiplatelet therapy = 4), and because blood tests on day four showed a drop of hemoglobin from an initial value of 12.0 to 8.5 g/dL, aspirin was discontinued on day six, and the patient was discharged on a combination of rivaroxaban 15 mg/day and clopidogrel 75 mg/day. Two weeks after the hospital discharge, the patient was readmitted to the emergency Figure 2. Percutaneous coronarycoronary intervention intervention in in the the patient patient case case described described in thein the case case vignette. vignette. (A) The(A) department, this time with an anterior ST-segment elevation myocardial infarction. Coronary Theright right coronary coronary artery artery lesion lesion was treated was treated with the with implant the implant of a Xience of a Xience Prime (2.75 Prime 28(2.75 mm) × 28 stent. mm) (B stent.)