Dual antiplatelet therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Superiority of Dual Antiplatelet Therapy (Thienopyridine Plus Aspirin) Over Coumadin Plus Aspirin in PCI Patients
Several studies during the early stent era demonstrated the superiority of the combination of ticlopidine plus aspirin over coumadin plus aspirin. has deployment [1][2][3][4][5]. While progress was made over coumadin, Ticlopidine itself was associated with side effects and complications which included neutropenia in > 1%, thrombotic thrombocytopenia purpura in 0.2%, rash, nauseaand diarrhea[6]. Given the improved side effect profile and the results of the CLASSICS study, clopidogrel has replaced ticlopidine as the thienopyridine of choice [7][8][9].
Data is Lacking Regarding the Safety and Efficacy of Thienopyridine Monotherapy Versus Thienopyridine Plus Aspirin Therapy in the Aspirin Intolerant Patient
One question that arises among patients who have aspirin hypersensitivity is the safety and efficacy of thienopyridine monotherapy in the mangement of the PCI patient including those who have been stented. There is one single center, small randomized trial purporting to compare the safety and efficacy of thienopyridine monotherapy to that of thienopyridine plus aspirin[10]. 378 stents were placed in 243 patients who were randomly assigned to treatment with either 2 x 250 mg of ticlopidine (n=121) or the combination of 2 x 250 mg ticlopidine + 100 mg aspirin (122 patients) daily. All patients received 500 mg of intravenous aspirin at the time of the procedure. Two hundred and thirty-seven patients (97.5%) were free from the primary endpoint of death, cardiac events and vascular access-site complications through three months with no differences between treatment groups. Although 2 stent thromboses were observed in the combined treatment group, none were observed in the ticlopidine monotherapy group. There are several important limitations to this study. One is the fact that all patients received a high (500 mg) intravenous aspirin during the PCI which would have led to significant levels of platelet inhibition over the next week due to irreversible acetylation and inhibition of prostaglandin H-synthase/cyclooxygenase[11]. This is a period of high vulnerability to stent thrombosis and ischemic complications[12]. Thus, this was not truly a study of thienopyridine monotherapy as all patients received intravenous aspirin. The study by Machraoui is also limited by its small sample size. Finally, the study administered ticlopidine, which is not a pro-drug and may be associated with a lower rate of hyporesponsiveness than clopidogrel.
Data Inidicating that the Addition of Aspirin to a Thienopyridine Improves Clinical Outcomes in Patients with Acute Coronary Syndromes
There is surrogate marker data indicating that the level of platelet inhibition is greater among patients in whom aspirin is added to a thienopyridine.[13][14][15] In one study, aspirin added to clopidogrel was associated with a greater degree of inhibition of collagen-induced aggregation. The level of platelet aggregation for the combination was only 16.4 +/- 2.4%, which is less than that for aspirin alone (36.5 +/- 4.2%) or clopidogrel alone (59.3 +/- 5.1%, 3 way p < 0.001).[16] Further, aspirin added to clopidogrel was more effective than either aspirin or clopidogrel alone after activation with low dose thrombin (p < 0.05).[17] In rabbit models of stent thrombosis, aspirin potentiated the antithrombotic activity of clopidogrel in the following models: 1)thrombosis induced by a silk thread; 2) thrombosis in stents placed in an arteriovenous shunt; 3) thrombus formation following electrical stimulation of the rabbit carotid artery; and 4) 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt.[18] The clinical benefit of adding aspirin to clopidogrel is also demonstrated indirectly by the following observation: among patients on clopidogrel, patients with stent thrombosis were more often resistant to aspirin.[19][20]
References
- ↑ Hall P, Nakamura S, Maiello L, et al. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation. Circulation 1996;93:215-222.
- ↑ Urban P, Macayo C, Rupprecht HJ, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: The multicenter aspirin and ticlopidine trial after intracoronary stenting (MATIS). Circulation 1998;98:2126-2132.
- ↑ Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996;334:1084-1089.
- ↑ Leon MG, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998;339:1665-1667.
- ↑ Bertrand ME, Legrand V, Boland J, et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (FANTASTIC) study. Circulation 1998;98:1597-1603.
- ↑ Steinhubl SR, Tan WA, Foody JM, et al., for the EPISTENT Investigators. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. JAMA 1999;281:806-810.
- ↑ Bertrand ME, Hans-Jürgen R, et al., for the CLASSICS Investigators. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting. Circulation 2000;102:624-629.
- ↑ Mueller C, Buttner JH, Petrerson J, et al. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents. Circulation 2000;101:590-593.
- ↑ Taniuchi M, Kurz HI, Smith SC, et al. Ticlid or Plavix Post-Stents (TOPPS) (Abstr). Circulation 1999;100(Suppl I):I-379
- ↑ Machraoui A, Germing A, Lindstaedt M, et al. Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting. Follow-up results of a randomized study. J Invas Cardiol 2001;13:431-436.
- ↑ Awtry EH, Loscalzo J. Aspirin. Cardiovascular Drugs. Circulation 2000;101:1206-1218.
- ↑ Wilson S, Rihal CS, Bell MR, et al. Timing of coronary stent thrombosis in patients treated with ticlopidine and aspirin. Am J Cardiol 1999;83:1006-1011.
- ↑ Makkar RR, Eigler NL, Kaul S, et al. Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis. Eur Heart J 1998;10:1538-1546.
- ↑ Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: Enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000;36:699-705.
- ↑ Cadroy Y, Bossavy J, Thalamas C, et al. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation 2000;101:2823-2828.
- ↑ Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: Enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000;36:699-705.
- ↑ Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: Enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000;36:699-705.
- ↑ Herbert JM, Dol F, Bernat A, Falotico R, Lalé A, Savi P (1998). "The antiaggregating and antithrombotic activity of clopidogrel is potentiated by aspirin in several experimental models in the rabbit". Thrombosis and Haemostasis. 80 (3): 512–8. PMID 9759636. Retrieved 2010-07-02. Unknown parameter
|month=ignored (help) - ↑ Eshtehardi P, Windecker S, Cook S, Billinger M, Togni M, Garachemani A, Meier B, Hess OM, Wenaweser P (2010). "Dual low response to acetylsalicylic acid and clopidogrel is associated with myonecrosis and stent thrombosis after coronary stent implantation". American Heart Journal. 159 (5): 891–898.e1. doi:10.1016/j.ahj.2010.02.025. PMID 20435201. Retrieved 2010-07-02. Unknown parameter
|month=ignored (help) - ↑ Wenaweser P, Hess O (2005). "Stent thrombosis is associated with an impaired response to antiplatelet therapy". Journal of the American College of Cardiology. 46 (5): CS5–6. PMID 16237868. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help)