“Triple Therapy” Rather Than “Triple Threat”

Zhao, Hongjin; Zhang, Zheng; Wang, Zhi-Hao; Li, Shaohua; Zhang, Yun; Zhong, Ming; Zhang, Wei

doi:10.1378/chest.09-3083

Cited by 87 publications

(23 citation statements)

References 47 publications

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“…A number of studies have assessed the risks and benefits of warfarin therapy in addition to ASA [6,7] or dual antiplatelet therapy (ASA and clopidogrel) [8] for the prevention of cardiovascular events in patients with ACS. These studies showed an improvement in cardiovascular outcomes compared with antiplatelet therapy alone, but this improvement was accompanied by an increase in major bleeding.…”

Section: Introductionmentioning

confidence: 99%

“…These studies showed an improvement in cardiovascular outcomes compared with antiplatelet therapy alone, but this improvement was accompanied by an increase in major bleeding. Currently, triple antithrombotic therapy with warfarin, ASA and clopidogrel is only recommended in patients at low risk of bleeding [8]. Warfarin is also associated with other limitations that often result in patients receiving inadequate prophylaxis or sub-optimal patient adherence.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

et al. 2012

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Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as clopidogrel, is effective for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, but there is still a substantial residual risk of recurrence. Although anticoagulant therapy with a vitamin K antagonist (e.g. warfarin) in conjunction with antiplatelet therapy has been shown to reduce the risk of cardiovascular events, the rates of bleeding were increased with these combination therapies; hence, triple therapy with warfarin is currently only recommended in patients at low risk of bleeding. In addition, there are other limitations associated with vitamin K antagonist therapy, including the need for routine coagulation monitoring and dose adjustment to maintain the treatment within the therapeutic range. Rivaroxaban is an oral, direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban will be given to patients who also receive antiplatelet therapy, such as clopidogrel. This randomized, non-blinded, three-way crossover study investigated the effect of rivaroxaban on bleeding time when coadministered with clopidogrel. In addition, the influence of clopidogrel on the safety, tolerability, pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27 healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were identified as clopidogrel responders and were then randomized to the following three treatments: (A) two doses of clopidogrel on two consecutive days (300 mg on day 1; 75 mg on day 2); (B) one dose of rivaroxaban (15 mg); or (C) a combination of treatments A and B (rivaroxaban given on day 2). All treatments were well tolerated. Bleeding time with coadministration of rivaroxaban and clopidogrel was significantly prolonged in four subjects, compared with either drug alone: combination treatment increased the overall least squares-means to 3.77 times baseline (90% confidence interval [CI] 2.82–4.73), compared with 1.13 times baseline (90% CI 0.17–2.09) with rivaroxaban and 1.96 times baseline (90% CI 0.10–2.91) with clopidogrel. Co-administration of clopidogrel had no significant effect on the pharmacokinetics of rivaroxaban and, when compared with rivaroxaban alone, had no further effects on Factor Xa activity or prothrombin time. Inhibition of ADP-stimulated platelet aggregation by clopidogrel was not affected by rivaroxaban. As expected, owing to the mode of action of each study drug, the results of this study demonstrated that coadministration of the Factor Xa inhibitor rivaroxaban and the antiplatelet clopidogrel increased the bleeding time in healthy subjects without affecting other pharmacokinetic or pharmacodynamic parameters of each drug.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

et al. 2012

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“…Determining the most effective antithrombotic regimens for patients with OAC and coronary intervention can be challenging, and several meta‐analyses8, 9 and expert consensus satetments10, 11 demonstrated that “triple is better” for these patients, mostly due to the decrease of cardiovascular and cerebrovascular events compared with the DAPT regimen. So far, there has been sufficient evidence to support the indispensability of OAC among patients with AF.…”

Section: Discussionmentioning

confidence: 99%

“…Determining the most effective antithrombotic regimens for patients with OAC after coronary intervention could be challenging, and triple therapy including OAC and DAPT was the preferred treatment compared with DAPT alone. In the past decade, several clinical trials4, 5, 6, 7 and meta‐analyses,8, 9 most of which were retrospective, small‐scale, and single‐center studies, indicated that triple therapy could reduce cardiovascular events, at the cost of increasing major bleeding risk compared with DAPT treatment. Therefore, before 2014, North American and European expert consensus statements recommended the combination of OAC and DAPT in the majority of AF patients receiving coronary stenting 10, 11.…”

Section: Introductionmentioning

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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“…In a study of patients with AF who underwent percutaneous coronary stenting, the risk of late major bleed was more than five times higher among those discharged with triple AT therapy [26]. Additionally, in a meta-analysis of 1,996 participants on chronic long-term AC therapy who underwent coronary artery stenting, the risk of major bleeding was doubled among patients discharged with triple therapy [27]. However, despite the higher reported risk of bleeding with triple therapy, the same study also reported a 40% reduction in major adverse cardiovascular events and a 41% reduction in all-cause mortality among those patients who received triple therapy.…”

Section: Discussionmentioning

confidence: 99%

Antithrombotic Therapy in Patients with Acute Coronary Syndrome in the Intermountain Heart Collaborative Study

Knight

Klaskala

Woller

et al. 2015

Cardiology Research and Practice

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Objective. To determine factors associated with single antiplatelet (SAP) or dual antiplatelet (DAP) therapy and anticoagulants (AC) use in hospital and after discharge among patients with acute coronary syndrome (ACS). Methods. We evaluated 5,294 ACS patients in the Intermountain Heart Collaborative Study from 2004 to 2009. Multivariable logistic regressions were used to determine predictors of AC or AP use. Results. In hospital, 99% received an AC, 79% DAP, and 19% SAP; 78% had DAP + AC. Coronary stents were the strongest predictors of DAP use in hospital compared to SAP (P < 0.001). After discharge, 77% received DAP, 20% SAP, and 9% AC; 5% had DAP + AC. DAP compared to SAP was less likely for patients on AC (odds ratio [OR] = 0.30, P < 0.0001) after discharge. Placement of a stent increased the likelihood of DAP (bare metal: OR = 54.8, P < 0.0001; drug eluting: OR = 59.4, P < 0.0001). 923 had atrial fibrillation and 337 had a history of venous thromboembolism; these patients had increased use of AC (29% and 40%, resp.). Conclusion. While in-hospital use of AC was nearly universal, postdischarge AC use was rare. Concern for providing the best antithrombotic therapy, while maintaining an acceptable bleeding risk, may explain the selection decisions.

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“Triple Therapy” Rather Than “Triple Threat”

Cited by 87 publications

References 47 publications

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

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

Antithrombotic Therapy in Patients with Acute Coronary Syndrome in the Intermountain Heart Collaborative Study

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