Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new plavix research articles will be listed here shortly after becoming available to us.
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Medical research on plavix
J Korean Med Sci. 2008 Jun; 23(3): 556-9
Lim SY, Kim KS, Joo SJ, Jeong MH
Very late stent thrombosis (VLST) after implantation of drug-eluting stent is rare, but very fatal complication after percutaneous coronary intervention. We report a case of VLST of a sirolimus-eluting Cypher(TM) stent (Cordis, Johnson and Johnson) presenting as acute ST elevation myocardial infarction at 26 months after deployment with continued combined dual antiplatelet medication of aspirin and clopidogrel. The patient did not show anti-platelet resistance.
Heart Surg Forum. 2008; 11(3): E152-7
Kayacioglu I, Gunay R, Saskin H, Idiz M, Sensoz Y, Ates M, Tangurek B, Alper AT, Demirtas MM, Yekeler I
Background. Reactive thrombocytosis has been reported in 20% of patients after coronary artery bypass grafting (CABG), a frequency that might be related to the high incidence of thrombotic complications. The present study was planned to investigate the effect of combined treatment with clopidogrel and acetylsalicylic acid (ASA) on post-CABG reactive thrombocytosis.Methods. Included in this prospective, randomized study were 60 patients who underwent CABG operation with a 6-month follow-up. Three study groups were defined: group 1 (n = 20), a control group of patients who have not developed reactive thrombocytosis after CABG surgery; group 2 (n = 20), patients who have developed reactive thrombocytosis and continue taking ASA (300 mg/day); and group 3 (n = 20), patients who have developed reactive thrombocytosis and continue taking ASA (300 mg/day) with the addition of clopidogrel (75 mg/day).Results. The mean ages and sex distributions of the patient groups were similar. There were no significant differences between the groups regarding cardiovascular risk factors, baseline laboratory findings, or intraoperative characteristics. Thrombocytosis disappeared within the first month after the operation in both treatment groups. An evaluation of graft patency in the sixth postoperative month revealed that group 2 had significantly more patients with a "positive" result in the exercise test than group 3 and that group 3 had a lower incidence of graft occlusion than group 2 (P < .01).Conclusions. Combination antiplatelet therapy with ASA and clopidogrel seems to be more effective than ASA alone for maintaining graft patency in patients with reactive thrombocytosis.
Antiplatelet agents for secondary prevention of stroke.
Curr Treat Options Cardiovasc Med. 2008 Jun; 10(3): 223-8
Bernstein RA
Patients with recent ischemic stroke or transient ischemic attack (TIA) face a high risk of recurrent stroke as well as an increased risk of myocardial infarction and sudden cardiac death. In the absence of a clearly established indication for long-term anticoagulation, such as atrial fibrillation, antiplatelet agents are the antithrombotic drugs of choice for preventing recurrent vascular events. For many years, aspirin (ASA) has been the first-line therapy for patients at high risk of vascular ischemic events. Two large clinical trials have established the superiority of the combination of ASA and extended-release dipyridamole (ASA/ERDP) over ASA alone in patients with recent noncardioembolic ischemic stroke or TIA. Clopidogrel, another antiplatelet agent, is a reasonable alternative to ASA, but its superiority to ASA in patients with a history of stroke has not been as clearly established. The combination of ASA and clopidogrel, which is effective in patients with acute coronary syndrome, has not been shown to be either effective or safe, compared with either agent alone, in stroke patients, although there may be some benefit to this combination in patients with acute TIA. The results from a large randomized trial comparing ASA/ERDP with clopidogrel, anticipated soon, will further assist clinicians in choosing among available antiplatelet agents.
[Platelet Function Analysis with Point-of-Care Methods.]
Herz. 2008 Jun; 33(4): 297-305
Görlinger K, Jambor C, Dirkmann D, Dusse F, Hanke A, Adamzik M, Hartmann M, Philipp S, Weber AA, Rahe-Meyer N
BACKGROUND: More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an increased risk of perioperative bleeding. In both situations control of the efficiency of therapy or rather the assessment of the impairment of hemostasis is of vital importance. METHODS: Platelet function analyzer (PFA-100((R))), multiple platelet function analyzer (Multiplate((R))), and rotational thrombelastometry (ROTEM((R))) are reliable and easy to use point-of-care (POC) devices. Since these three analyzers monitor different aspects of platelet function and have different limitations, the selection of the right test system depends on the right question. RESULTS: PFA-100((R)) enables a sensitive detection of von Willebrand's syndrome. Multiplate((R)) is apt to control efficiency of platelet inhibiton with acetylsalicylic acid, clopidogrel and glycoprotein IIb/IIIa receptor antagonists. ROTEM((R)) analysis offers the opportunity to assess hemostasis as a holistic system. Thereby, ROTEM((R)) analysis particularly detects hyperfibrinolysis, heparin effects, and fibrinogen-platelet interaction. CONCLUSION: Due to their easy handling the described POC devices are applicable to perioperative coagulation management as well as during and after coronary intervention or to monitoring of platelet function in cardiologic practice. They enable a quick assessment of platelet function and an individually guided therapy.
Methods to Evaluate the Pharmacology of Oral Antiplatelet Drugs.
Herz. 2008 Jun; 33(4): 287-296
Weber AA, Adamzik M, Bachmann HS, Görlinger K, Grandoch M, Leineweber K, Müller-Beißenhirtz H, Wenzel F, Naber C,
Principally, there are two reasons why the pharmacological response to antiplatelet drugs should be measured: on the one hand, an insufficient inhibition of platelet function may result in atherothrombotic complications; on the other hand, an excessive inhibition of platelet function may lead to bleeding complications. The clinical importance to measure the effects of antiplatelet drugs is demonstrated by increasingly growing evidence for an association of resistance to antiplatelet drugs with thromboembolic events. It is often claimed that there is no generally accepted definition of "resistance" and, instead, there is an ongoing semantic discussion about the correct term to be used to describe this phenomenon. From the pharmacological point of view, there is only one acceptable definition of "resistance" to antiplatelet drugs: the term "resistance" should be used when a drug is unable to hit its pharmacological target. Thus, laboratory methods used to evaluate the effects of antiplatelet drugs should be designed to measure the direct pharmacodynamic effect of a drug, rather than the consequences for global platelet function. Based on physiological/pathophysiological, pharmacological, and practical considerations, the authors propose the following assays to be used to measure the effects of oral antiplatelet drugs: for the detection of aspirin actions, thromboxane or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured; for the detection of clopidogrel actions, VASP (vasodilator-stimulated phosphoprotein) phosphorylation (flow cytometry) or ADP-(adenosine diphosphate-)induced responses (light aggregometry, whole-blood aggregometry, possibly also flow cytometry) should be measured.
[Clopidogrel - clinical use and potential therapeutic problems.]
Herz. 2008 Jun; 33(4): 280-6
Schäfer A, Bauersachs J, Eigenthaler M
Platelet activation is a major component in the pathogenesis of coronary thrombosis and myocardial infarction. Therefore, antiplatelet therapy has become the cornerstone in the therapy of ischemic heart disease. Thienopyridines, especially clopidogrel, have a highly significant effect on treated patients with regard to reduction of stent thrombosis and functional inhibition of adenosine diphosphate-(ADP-)induced platelet activation. Clopidogrel, a specific inhibitor of the P2Y(12) ADP receptor, is a prodrug which releases the active compound after metabolization. Actual ACC/AHA/SCAI guidelines recommend the use of 75 mg clopidogrel once daily after stent implantation. Nevertheless, there is a high incidence of impaired clopidogrel responsiveness in patients potentially leading to subacute stent thrombosis and other adverse cardiovascular events following coronary interventions (incidence of about 1% within the first 4 weeks). Therefore, individual risk testing and adjusted antiplatelet therapy might be recommendable under certain circumstances, e.g., high-risk interventions such as last patent vessel, dominant vessel, or planned drug-eluting stent implantation. Furthermore, identification of a nonresponder requires increased clinical attention. Newly developed antiplatelet substances might overcome the nonresponse problem and allow sufficient platelet inhibition in all patients. Further prospective studies are needed to determine the risk reduction by an individually adjusted antiplatelet therapy.
[Resistance to Antiplatelet Substances - a Real Clinical Problem.]
Herz. 2008 Jun; 33(4): 260-268
Geisler T, Gawaz M
The benefit of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel in cardiovascular risk patients has been documented by several studies. Patients undergoing coronary interventions are in jeopardy of periinterventional thrombotic complications, and stent thrombosis, although a rare event, is still a serious problem, especially in the era of drug-eluting stents. Recently, there is a growing body of evidence that response to antiplatelet therapy is a clinically important entity and subjects presenting a low response to conventional antiplatelet substances are at increased risk for atherothrombotic events. Thereby, aspirin and clopidogrel resistance have been considered a multifactorial phenomenon underlying factors ranging from nonadherence of patients to antiplatelet therapy to demographic characteristics (age, diabetes, renal failure, etc.), acute coronary syndromes as well as genetic polymorphisms involving platelet glycoproteins and cytochrome P450 isoenzymes. The introduction of point-of-care platelet function tests into clinical routine is a still ongoing process, partly because of missing common definitions of resistance, partly due to different laboratory methods that prevent transferability of results. However, first approaches of an adoption of antiplatelet therapy guided by platelet function analysis provide promising results that an individualized antiplatelet strategy might help to improve platelet inhibition in cardiovascular patients. If this will improve clinical outcome has to be evaluated in upcoming studies. The aim of the present article is to give a review about the clinical relevance of resistance to antiplatelet therapy and alternative treatment options.
[Surgical Procedures in Patients Treated with Platelet Function Inhibitors.]
Herz. 2008 Jun; 33(4): 254-259
Rupprecht HJ, Blank R, Konradi D, Andreas K, Auerbach H
The platelet function inhibitors (PFI) acetylsalicylic acid (ASA) and clopidogrel are widely used in a broad spectrum of atherothrombotic diseases, either as mono- or dual antiplatelet therapy. Platelet function is inhibited for the whole lifespan of platelets (10 days). In case of surgical procedures the bleeding risk under continued antiplatelet therapy has to be balanced against the risk of ischemic complications due to withdrawal of antiplatelet therapy. Especially after stent implantation, the high risk and unfavorable prognosis of stent thrombosis have to be considered. Whereas surgical procedures with a low bleeding risk may be performed with continued antiplatelet therapy, there is a need for partial or total discontinuation of antiplatelet therapy in surgical procedures with higher bleeding risks.
[Optimal platelet inhibition after coronary stent implantation. Current status.]
Herz. 2008 Jun; 33(4): 244-53
Silber S, Hoffmeister HM, Bode C
Percutaneous coronary intervention (PTCA, PCI) is the most frequently used therapy for the treatment of stenoses or occlusions of coronary arteries. In Germany, six PCIs are performed for every coronary bypass surgery. Today, stents are implanted in over 80% of PCIs to improve the acute and long-term results. The most feared complication after stent implantation is the acutely occurring stent thrombosis, which usually leads to a myocardial infarction with its relatively high mortality. The introduction of platelet inhibition (acetylsalicylic acid [ASA] and ticlopidine/clopidogrel) decreased the rate of early ( 30 days to 1 year) or very late (> 1 year) stent thromboses after BMS, but they do occur. Whereas a dual platelet inhibition of 4 weeks is sufficient after BMS, it must be performed longer after DES due to its prolonged period of endothelialization. In the randomized DES versus BMS studies, the rates of late and very late stent thromboses were increased with DES in the range of approximately 1 per thousand annually - but without affecting the mortality. DES may prevent myocardial infarctions by reducing restenoses, thus offsetting the possibly negative effects of late stent thrombosis. In patients with more extensive disease, previously sent to bypass surgery, the rate of late and very late stent thromboses is in the range of 0.6% per year. Since there is no control group from major randomized studies for these patients, more data have to be awaited.The optimal duration of dual platelet inhibition after DES is unknown, since no prospective, randomized trials have addressed this question. Based on the presently available data, clopidogrel must be given in addition to ASA for at least 6 months. Depending on the individual risk of stent thrombosis and the individual risk of bleeding, clopidogrel can be administered for 1 year or longer. Although a diminished effect of ASA and/or clopidogrel is known to be present in some patients, laboratory testing of platelet aggregation cannot be recommended for clinical decision- making at the present time due to missing standards and lack of pivotal studies. For clopidogrel, an increased platelet inhibition has been described with double dose (75 mg bid), but the clinical relevance is unknown. Whether new thienopyridine derivatives, like prasugrel, will also be superior to clopidogrel under "everyday" conditions has still to be shown. In patients with proven indication for chronic anticoagulation, the use of DES should be restricted or avoided. If a DES was nevertheless implanted, triple therapy (coumadin, ASA, and clopidogrel) is recommended - with an INR (International Normalized Ratio) target of 2.0, possibly adding a proton pump inhibitor. In case of nondeferrable surgery, dual platelet inhibition should be continued, if possible (like dental extractions), or perioperatively converted to a small-molecule glycoprotein IIb/IIIa inhibitor - under in-hospital survey. Further developments of next-generation DES with different drugs, modified release kinetics, specifically abluminal drug release or bioabsorbable polymers or absorbable stents are necessary, in order to reduce the duration of dual platelet inhibition to the range of BMS - but maintaining the well-established antiproliferative effects of DES.
Int J Cardiol. 2008 Jun 23;
Shim CY, Yoon SJ, Park S, Kim JS, Choi JR, Ko YG, Choi D, Ha JW, Jang Y, Chung N, Shim WH, Cho SY
BACKGROUND: Triple antiplatelet therapy may have a beneficial effect on prevention of thrombotic complication in patients undergoing coronary stenting. We investigated the prevalence of aspirin and clopidogrel resistance in patients treated with dual and triple antiplatelet regimen after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: A total of 400 consecutive patients underwent successful PCI with DES were randomly assigned to therapy with dual antiplatelet regimens (aspirin plus clopidogrel, Group I, n = 200) and triple antiplatelet regimens (aspirin plus clopidogrel plus cilostazol, Group II, n = 200) At two weeks after PCI, aspirin and clopidogrel resistance were assayed in 379 patients (Group I, n = 186; Group II, n = 193) by using the VerifyNow System. RESULTS: In Group I, 21 (11.3%) patients had aspirin resistance and 74 (40.0%) had clopidogrel resistance. In Group II, 19 (9.8%) were resistant to aspirin and 38 (19.7%) to clopidogrel. The aspirin reaction unit (ARU) was not significantly different between groups (448+/-67 vs. 439+/-64, P = 0.200), but the percent inhibition of clopidogrel was higher in Group II (41.4+/-24.3%,) comparing with that of Group I (26.5+/-18.7%, P < 0.001). CONCLUSION: With triple antiplatelet therapy, the prevalence of clopidogrel resistance can be attenuated in patients undergoing PCI with DES.