Ticagrelor Versus Clopidogrel as Part of Dual or Triple Antithrombotic Therapy: a Systematic Review and Meta-Analysis

Purpose

Clopidogrel is the standard P2Y₁₂ receptor inhibitor used in patients requiring both antiplatelet therapy and oral anticoagulation (OAC). We investigated the safety and efficacy of ticagrelor as an alternative to clopidogrel in patients on OAC.

Methods

A systematic electronic literature search was performed in MEDLINE, EMBASE, and the Cochrane Library for randomised controlled studies that examined the relative safety and efficacy of clopidogrel versus ticagrelor among patients requiring therapy with antiplatelet agents plus OAC.

Results

Three randomised controlled trials were identified with a total of 5659 patients. The risk of clinically significant bleeding was significantly increased among patients on dual or triple antithrombotic therapy who received ticagrelor compared with patients on clopidogrel (OR 1.52, 95% CI 1.12 to 2.06, and OR 1.7, 95% CI 1.24 to 2.33, respectively). Among those on triple therapy, ticagrelor was associated with a significantly higher risk of major adverse cardiovascular events (MACE) compared to clopidogrel (OR 1.88, 95% CI 1.26 to 2.80). Patients who received dual therapy exhibited similar risk of MACE and stroke with ticagrelor versus clopidogrel (OR 1.14, 95% CI 0.83 to 1.56, and OR 0.42, 95% CI 0.10 to 1.74, respectively).

Conclusion

The use of ticagrelor as part of dual or triple antithrombotic therapy is associated with significantly higher rates of clinically relevant haemorrhagic complications compared with clopidogrel. Among triple therapy-treated patients, the use of ticagrelor might increase thromboembolic and ischaemic cardiac events.

     

Antiplatelet Therapy in Interventional Cardiology: I. Newer Oral Antiplatelet Agents

Journal of Thrombosis and Thrombolysis -     

Antiplatelet Therapy in Interventional Cardiology: II. Glycoprotein IIb/IIIa Inhibitors

Journal of Thrombosis and Thrombolysis -     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Aspirin Versus Dual Antiplatelet Therapy in Patients Undergoing Trans-Catheter Aortic Valve Implantation,Updated Meta-Analysis

Cardiovascular Drugs and Therapy - The Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic-Valve Implantation (POPular TAVI) trial reported comparable composite endpoints of ischemic...     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

Successful Therapy With Ticagrelor in Three-Vessel Stent Thrombosis Related to Clopidogrel Resistance

A 65-year-old man developed 3-vessel stent thrombosis after percutaneous coronary intervention with aspirin and clopidogrel. Platelet tests revealed clopidogrel resistance, which resolved after changing clopidogrel to ticagrelor. Although routine platelet tests after stenting are not recommended, these tests may be considered to identify the cause of stent thrombosis and modify antiplatelet therapy.     

Single Versus Dual Antiplatelet Therapy following Left Atrial Appendage Occlusion in Patients With High Bleeding Risk

Our study aims to compare the utility of single antiplatelet therapy (SAPT) with dual antiplatelet therapy (DAPT) following Left atrial appendage occlusion in patients whose post-procedural oral anticoagulation therapy was deemed high-risk or contraindicated. A total of 14 observational studies with 3,151 patients were included. Our study demonstrates that SAPT and DAPT were similar in preventing device-related thrombosis. Although SAPT and DAPT had a tendency toward a higher risk for stroke and major bleeding respectively, these differences did not reach statistical significance. Large-scale Randomized Controlled Studies are warranted to validate if our results could be translated into clinical practice.     

Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus

ObjectivesThe aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned.BackgroundThe efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown.MethodsThis pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization).ResultsThe primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm–by–diabetic status interaction (p_int = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500).ConclusionsDM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800)