Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting

Karjalainen, Pasi P.; Porela, Pekka; Ylitalo, Antti; Vikman, Saila; Nyman, Kai; Vaittinen, Mari-Anne; Airaksinen, Tuukka J; Niemelä, Matti; Vahlberg, Tero; Airaksinen, K. E. Juhani

doi:10.1093/eurheartj/ehl488

Cited by 261 publications

(206 citation statements)

References 28 publications

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“…[1][2][3] Oral anticoagulation therapy with vitamin K antagonists reduces the incidence of recurrent ischemic events after myocardial infarction but also increases the risk of bleeding when it is added to aspirin or aspirin and clopidogrel. [4][5][6][7][8][9] Apixaban, an orally active, selective, direct factor Xa inhibitor, has been shown to reduce the incidence of venous thromboembolism in patients undergoing orthopedic surgery and to prevent thromboembolic events in patients with atrial fibrillation who are not candidates for oral vitamin K antagonist therapy. [10][11][12][13][14][15] We previously studied the use of apixaban, at doses of 5 to 20 mg daily, in patients who had had recent acute coronary syndromes and who were receiving aspirin or aspirin plus clopidogrel.…”

mentioning

confidence: 99%

Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

Alexander

Lopes

James³

et al. 2011

N Engl J Med

914

532

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mentioning

confidence: 99%

Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

Alexander

Lopes

James³

et al. 2011

N Engl J Med

914

532

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“…From 625 initial citations, 16 eligible studies including a total of 9185 patients were identified in the present meta‐analysis,4, 5, 6, 7, 12, 14, 15, 19, 20, 21, 22, 23, 24, 25, 26, 27 with 5680 patients in the triple therapy group and 3505 in the dual therapy group (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

“…Finally, 12 studies were identified in the DAPT subgroup,4, 5, 6, 7, 19, 20, 21, 22, 23, 24, 25, 26 with the other 4 studies included in the OAC/C subgroup 12, 14, 15, 27…”

Section: Resultsmentioning

confidence: 99%

Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta‐analysis of 16 Clinical Trials and 9185 Patients

Gao

Chen

Fan

et al. 2015

Clinical Cardiology

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The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation. Medline, the Cochrane Library, and other Internet sources were searched for clinical trials comparing the efficacy and safety of triple vs dual therapy for patients taking OAC after coronary stenting. Sixteen eligible trials including 9185 patients were identified. The risks of major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.82‐1.39, P = 0.65), all‐cause mortality (OR: 0.98, 95% CI: 0.76‐1.27, P = 0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77‐1.31, P = 0.97), and stent thrombosis (OR: 0.91, 95% CI: 0.49‐1.69, P = 0.75) were similar between triple and dual therapy. Compared with dual therapy, triple therapy was associated with a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35‐0.94, P = 0.03) but with higher major bleeding (OR: 1.52, 95% CI: 1.11‐2.10, P = 0.01) and minor bleeding (OR: 1.59, 95% CI: 1.05‐2.42, P = 0.03). Subgroup analysis indicated there were similar ischemic stroke and major bleeding outcomes between triple therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel was associated with similar efficacy and safety outcomes compared with triple therapy. Triple therapy could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events.

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“…Indeed, because blockade of P2Y 12 receptor–mediated signaling with clopidogrel is associated with greater platelet‐inhibitory effects than cyclooxygenase‐1 inhibition with aspirin, as well as the established role of P2Y 12 receptor blockade on recurrent thrombotic events, clopidogrel might be expected to be more effective than aspirin at reducing risk of ST, with a potentially lower rate of gastrointestinal bleeding as well 40. A few retrospective cohorts have observed a lower incidence of ST with clopidogrel plus warfarin dual antithrombotic therapy,13, 20, 41 and clopidogrel, aspirin, and warfarin triple antithrombotic therapy,42 compared with warfarin and aspirin dual antithrombotic therapy.…”

Section: Discussionmentioning

confidence: 99%

Design and Rationale of the RE‐DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting

Cannon

Gropper

Bhatt

et al. 2016

Clinical Cardiology

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Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest‐sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE‐DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open‐label, blinded‐endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low‐dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ∼ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.

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Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting

Abstract: Our study shows that the prognosis is unsatisfactory in warfarin-treated patients irrespective of the drug combination used. Aspirin plus warfarin combination seems to be inadequate to prevent stent thrombosis.

Cited by 261 publications

References 28 publications

Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta‐analysis of 16 Clinical Trials and 9185 Patients

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