A 77-year-old man presents to the emergency department with chest pain. He reports a progressive decline in his exercise capacity over the past 6 months due to worsening chest pain with activity. Today, he was playing with his grandchildren when he developed sudden onset of severe, sub-sternal chest pain. After 30 minutes of rest, his pain persisted and he was still unable to catch his breath, prompting him to seek medical care.
His past medical history is notable for atrial fibrillation, hypertension, hyperlipidemia, and type 2 diabetes mellitus. There is no history of heart failure, stroke or TIA. The outpatient medications include lisinopril, metoprolol, atorvastatin, and warfarin, titrated to an INR goal of 2.0-3.0 (for atrial fibrillation with CHADS2 = 3).
Laboratory values are notable for an elevated troponin and CK-MB. Electrocardiogram shows 3-4 mm ST depressions in leads V2-V5. Coronary angiography reveals a 95% stenosis of the proximal left anterior descending artery, for which a bare metal stent is placed.
He spends two days in the hospital without complications.
At the time of discharge, what is the most appropriate antithrombotic strategy for this patient?
Show Answer
The correct answer is: B) Warfarin, aspirin 81 mg, and clopidogrel 75 mg
At this time, based on current evidence and guidelines, the most appropriate antithrombotic strategy in patients with atrial fibrillation (AF) and moderate-to-high stroke risk who undergo percutaneous coronary intervention (PCI) is triple antithrombotic therapy (TOAT) for at least one month after stent placement. The evidence for this therapy is limited to retrospective studies and extrapolations from older randomized trials that studied the addition of warfarin to aspirin in acute coronary syndrome (ACS). Given the limited data, only a few consensus guidelines have been published on this topic, all of which recommend TOAT for at least some period of time in most patients with AF who undergo stent placement.1-3
One set of recommendations for antithrombotic therapy in patients with AF after PCI was published in Circulation: Cardiovascular Interventions in 2011 (Table 1).2 For patients with very low stroke risks (CHADS2 = 0), the authors recommend using dual anti-platelet therapy (DAPT) without oral anticoagulation (OAC) for 1 year after PCI. For all other patients, they recommend TOAT after stent placement for 1-6 months, depending on the type of stent placed and the individual risks of stroke and stent thrombosis.
Stroke Risk
Bleeding Risk
Stent Thrombosis Risk
Type of Stent
Recommendation
CHADS2 = 0
Any
Any
BMS or DES
0-12 months: DAPT After 12 months: OAC*
CHADS2 > 0
Low
Low
BMS
0-1 months: TOAT 1-12 months: OAC+SAPT After 12 months: OAC*
DES
0-6 months: TOAT 6-12 months: OAC+SAPT After 12 months: OAC*
High
BMS
0-6 months: TOAT 6-12 months: OAC+SAPT After 12 months: OAC*
DES
0-12 months: TOAT After 12 months: OAC*
High
Any
BMS
0-1 months: TOAT 1-12 months: OAC+SAPT After 12 months: OAC*
Table1: Recommendations from Faxon et al. in Circulation: Cardiovascular Interventions for antithrombotic therapy in patients with atrial fibrillation after coronary stent placement *The authors note that in patients at high risk for atherothrombotic events including stent thrombosis, long-term OAC and SAPT should be considered after 12 months instead of OAC alone. BMS - bare metal stent, DES - drug-eluting stent, SAPT - single antiplatelet therapy
The American College of Chest Physicians (ACCP) also published recommendations for antithrombotic therapy in patients with AF after PCI.1 Similar to those in Circulation, they recommend omitting OAC and using DAPT only for 1 year after stent placement in patients at low risk of stroke (CHADS2 = 0 or 1). For patients with higher stroke risks, they recommend 1-6 months of TOAT after PCI depending on the stent type. The European Society of Cardiology (ESC) Working Group on Thrombosis also released a consensus document regarding the management of these patients.3 These recommendations differ slightly in that they do not advise holding OAC at any time regardless of stroke risk. The advised duration of TOAT varies from 1-6 months depending on bleeding risk, stent type, and clinical setting.
Choice C suggests using OAC plus clopidogrel while omitting aspirin. The best evidence for this strategy comes from the recently published What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing (WOEST) trial.4 The authors randomized 573 patients on OAC scheduled to undergo PCI to either double therapy (warfarin and clopidogrel 75 mg) or triple therapy (warfarin, clopidogrel 75 mg, and aspirin 80 mg). Patients receiving triple therapy experienced a significantly higher cumulative incidence of the primary endpoint of all Thrombolysis in Myocardial Infarction (TIMI) bleeding (44.4% vs. 19.4%; HR 0.36; 95% CI 0.26–0.50; P < 0.0001). Patients assigned to double therapy experienced a significant reduction in the composite of death, myocardial infarction (MI), stroke, systemic embolism, target vessel revascularization, and stent thrombosis (11.1 vs. 17.6%; HR 0.56; 95% CI 0.35–0.91; P = 0.025), as well as a significant reduction in mortality (2.5 vs. 6.3%; HR 0.39; 95% CI 0.16–0.93; P = 0.027) and non-significant reductions in MI, stroke, and stent thrombosis.
The latest ESC recommendations on the use of new anticoagulants in AF mention that, for patients with AF after ACS, "clopidogrel plus [a vitamin-K antagonist] appears to be the most sensible combination early after PCI in AF patients."5 While larger studies are needed to confirm the WOEST findings, OAC plus clopidogrel might be the preferred strategy for these patients, especially those at low risk of stent thrombosis and high risk of bleeding.
Choice D suggests an interesting strategy that has yet to be directly studied. ATLAS ACS 2-TIMI 51 found rivaroxaban 2.5 mg twice daily to be associated with significant reductions in cardiovascular death, MI, or stroke (9.1% vs. 10.7%, P=0.02) and all-cause mortality (2.9% vs. 4.5%, P=0.002), compared to placebo, when added to post-ACS medical regimens, 93 percent of which included DAPT.6 Patients with AF were excluded from this trial and it is unclear if this lower-dose regimen (2.5 mg twice daily) would provide adequate stroke reduction in patients with AF (20 mg once daily was studied in the ROCKET-AF trial). The PIONEER AF-PCI trial is an ongoing study comparing three antithrombotic strategies in patients with AF undergoing PCI: rivaroxaban 2.5 mg twice daily, a P2Y12 inhibitor, and aspirin 75-100 mg daily; rivaroxaban 15 mg once daily and a P2Y12 inhibitor; and a vitamin K antagonist, a P2Y12 inhibitor, and aspirin 75-100 mg daily. Among other things, this trial promises to shed light on the utility of the TOAT regimen used in ATLAS ACS 2-TIMI 51 in patients with AF after PCI.
The patient presented in this case requires an antithrombotic strategy that best balances his risks of stroke, stent thrombosis, and bleeding. While the evidence supporting an ideal strategy is limited, TOAT is probably the most reasonable therapy. The few published recommendations agree with this strategy and would advise TOAT for at least 1 month after PCI in this patient.
References
You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e531S-575S
Faxon DP, Eikelboom JW, Berger PB, et al. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: A North American perspective: Executive summary. CirculationCardiovascular interventions. 2011;4:522-534
Lip GY, Huber K, Andreotti F, et al. Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: Executive summary--a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2010;31:1311-1318
Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet. 2013;381:1107-1115
Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651
Mega JL, Braunwald E, Wiviott SD,et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19
Log in to MyACC
