Triple Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing PCI: Adequate Time in Therapeutic INR Range
Received Date: Apr 26, 2017 / Accepted Date: May 03, 2017 / Published Date: May 05, 2017
Dual anti-platelet therapy (DAPT) is a standard procedure for patients undergoing percutaneous coronary intervention (PCI) using stents [1,2], whereas oral anticoagulation (OAC) is necessary, when CHADS2-VASc scores are ≥ 2, to reduce stroke and embolic events in patients with atrial fibrillation (AF) [3,4]. Coronary artery disease (CAD) and AF often coexists in same patient, approximately 5-10% of patients who underwent PCI have AF [5,6]. Some studies have reported that DAPT with OAC (triple antithrombotic therapy [TT]) reduces major cardiovascular events and mortality compared with DAPT only in patients who underwent PCI with AF [7,8]. On the other hand, others have found that TT increases the bleeding and cardiovascular events [9,10]. Therefore, the optical combination antithrombotic therapy for the patients with AF undergoing PCI is uncertain.
The 2012 American College of Chest Physicians (ACCP) guidelines recommended TT (eg. OAC, aspirin and clopidogrel) for patients with AF (CHADS2 score of 2 or greater) who undergoing PCI during the first month after placement of a bare-metal stent or first 3 to 6 months after placement of a drug-eluting stent. After this initial period of TT, OAC plus a single antiplatelet drug is recommended. At 12 months after PCI, OAC alone is suggested as for patients with AF and CAD (Grade 2C) . The 2016 European Society of Cardiology (ESC) guidelines recommended TT during the first month after PCI (stable CAD and acute coronary syndrome with high bleeding risk) or first 6 months after PCI (acute coronary syndrome with low bleeding risk). After that, recommendation of antithrombotic therapy was same as the 2012 ACCP guidelines (class IIa, evidence level B or C) . When a direct oral anticoagulant (DOAC) is used as for OAC, the consensus recommendation is that the lowest dose effective for stroke prevention in AF should be considered.
Recently, DOAC is broadly used as for OAC instead of vitamin K antagonism (VKA) in patients with AF and venous thromboembolism. However, the patients of chronic kidney disease, high age and lean do not have the adaptation of DOAC. Among the patients with AF who undergoing PCI, the patients who do not have the adaptation of DOCA are not a little and these patients need to use VKA as for OAC. Therefore, one of critical issue of TT is still unclear regarding appropriate range of international normalized ratio of prothrombin time (PT-INR). In patients, who receive TT, the recommended range for the PT-INR varies between 2.0 and 2.5 in the ESC guidelines (class IIa, evidence level C)  and between 2.0 and 3.0 in the ACCP guidelines (grade 2C) . However, a PT-INR value using TT has not been established. An open-label, multicenter, randomized, controlled trial (WOEST trial)  compared bleeding and thrombotic events between TT and double antithrombotic therapy (clopidogrel and warfarin) in patients undergoing PCI who required OAC. TT was associated with a significant increase in bleeding complications. In WOEST trial, target range of PT-INR was set between 2.0 and 3.0, and the control of PT-INR (time in the therapeutic range [TTR]) was unclear. From WOEST study, range of PT- INR (2.0-3.0) might inappropriate in therapeutic INR range in patients with TT. Therefore, we investigated whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients with TT . We compared the outcomes between TT and DAPT in patients who underwent PCI using drug-eluting stents. Most of patients using DAPT did not have history of af. In our institute, the mean PT-INR was 1.8 ± 0.2 and the median TTR was 78.4% (inter-quartile range: 67.4-87.6) if the target level of PT-INR was set between 1.6 and 2.6 in TT group. The incidence of cardiovascular events and major bleeding events did not significantly differ between two groups (TT and DAPT group). This finding was consistent with J-RHYTHM Registry, which showed that a relatively low PT-INR range of 1.6-2.6 was safe and prevented thromboembolic or bleeding events in patients with AF . In general, the target range of PT-INR is higher in the USA and Europe compared with Japan. However, the BAATAF and SPINAF studies performed outside Japan set the target range for PT-INR at 1.5-2.7, and at 1.4-2.8 in patients with AF [17,18], respectively. These studies found that a low PT-INR reduced the incidence of thromboembolic events in patients with AF. Furthermore, Rossini and colleague reported that PT-INR >2.6 was the only independent predictor of bleeding among patients who underwent PCI and required TT . Therefore, it is possible that PT-INR 1.6-2.6 is acceptable and safe for patients who undergo PCI and require TT. Furthermore, it goes without saying, careful warfarin control is necessary.
This issue of TT is still controversy. Ongoing trials will inform about combination therapies in the future.
- Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, et al. (2011) 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 124: e574-e651.
- Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. (2013) 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 34: 2949-3003.
- European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, et al. (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31: 2369-2429.
- Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, et al. (2011) 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 123: e269-e367.
- Sørensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson C, et al. (2009) Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet 374: 1967-1974.
- Pérez-Gómez F, Alegría E, Berjón J, Iriarte JA, Zumalde J, et al. (2004) Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. J Am Coll Cardiol 44: 1557-1566.
- Ruiz-Nodar JM, Marín F, Hurtado JA, Valencia J, Pinar E, et al. (2008) Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis. J Am Coll Cardiol 51: 818-825.
- Karjalainen PP, Porela P, Ylitalo A, Vikman S, Nyman K, et al. (2007) Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 28: 726-732.
- Gilard M, Blanchard D, Helft G, Carrier D, Eltchaninoff H, et al. (2009) Antiplatelet therapy in patients with anticoagulants undergoing percutaneous coronary stenting (from STENTIng and oral antiCOagulants [STENTICO]). Am J Cardiol 104: 338-342.
- Lamberts M, Olesen JB, Ruwald MH, Hansen CM, Karasoy D, et al. (2012) Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation 126: 1185-1193.
- You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, et al. (2012) Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141: e531S-75S.
- Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, et al. (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37: 2893-2962.
- European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, et al. (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31: 2369-2429.
- Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, et al. (2013) 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 381: 1107-1115.
- Konishi H, Miyauchi K, Kasai T, Tsuboi S, Ogita M, et al. (2016) Adequate time in therapeutic INR range using triple antithrombotic therapy is not associated with long-term cardiovascular events and major bleeding complications after drug-eluting stent implantation. J Cardiol 68: 517-522.
- Inoue H, Okumura K, Atarashi H, Yamashita T, Origasa H, et al. (2013) Target international normalized ratio values for preventing thromboembolic and hemorrhagic events in Japanese patients with non-valvular atrial fibrillation: results of the J-RHYTHM Registry. Circ J 77: 2264-2270.
- Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators, Singer DE, Hughes RA, Gress DR, Sheehan MA, et al. (1990) The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 323: 1505-1511.
- Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, et al. (1992) Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 327: 1406-1412.
- Rossini R, Musumeci G, Lettieri C, Molfese M, Mihalcsik L, et al. (2008) Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol 102: 1618-1623.
Citation: Konishi H, Miyauchi K, Daida H (2017) Triple Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing PCI: Adequate Time in Therapeutic INR Range. Atheroscler open access 2: 110.
Copyright: © 2017 Konishi H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Select your language of interest to view the total content in your interested language
Share This Article
April 19-20, 2018 Amsterdam, Netherlands
May 14-16, 2018 Tokyo, Japan
June 11-13, 2018 Barcelona, Spain
August 09-10, 2018 Manila, Philippines
September 21-22, 2018 Vancouver, Canada
- Total views: 574
- [From(publication date): 0-2017 - Mar 20, 2018]
- Breakdown by view type
- HTML page views: 516
- PDF downloads: 58