[Thienopyridines in the treatment and prevention of cardiovascular diseases. III. therapeutic application of clopidogrel as monotherapy (without acetylsalicylic acid)].

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the third communication we consider data of randomized studies in which efficacy and safety of clopidogrel monotherapy has been assessed in comparison with acetylsalicylic acid (ASA), ticlopidine, warfarin, as well as ASA in combination with extended release form of dipyridamole in various cardio-vascular diseases. Results of these studies indicate that efficacy of monotherapy with clopidogrel is comparable with that of ASA, ticlopidine, warfarin, and ASA in combination with extended release form of dipyridamole. Clopidogrel significantly more rarely causes ulcerogenic and other hemorrhagic complications than ticlopidine, but is substantially more expensive. Therefore prescribing of clopidogrel as monotherapy is justified only in those cases when ASA and ticlopidine are contraindicated or induce pronounced side effects.

[Thienopyridines in the treatment and prevention of cardiovascular diseases. Part IV. therapeutic application of clopidogrel in combination with acetylsalicylic acid in acute coronary syndromes and percutaneous coronary interventions].

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the forth communication we consider data of randomized studies in which efficacy and safety of clopidogrel in combination with has acetylsalicylic acid (ASA) been assessed in comparison with (ASA) in various acute coronary syndromes (ACS), as well as before, during, and after percutaneous coronary interventions (PCI). In ACS it is recommended to start therapy with clopidogrel with 300 mg loading dose with subsequent transition to maintenance dose 75 mg/day. Preliminary therapy with clopidogrel (in combination with ASA) before emergent or elective PCI significantly decreases risk of development of unfavorable clinical outcomes. In PCI loading dose of clopidogrel is 300-600 mg while duration of maintenance therapy (75 mg/day) depends on the type of used coronary stent. After implantation of bare stent duration of therapy with clopidogrel should be not less than 1 month (ideally no less that 12 months) and after implantation of drug-eluting stent - not less than 12 months.

[Thienopyridines in the treatment and prevention of cardiovascular diseases. Part II. Clinical pharmacology of clopidogrel].

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the second communication we describe in detail clinical pharmacokinetics and pharmacodynamics of the most often used thienopyridine derivative - clopidogrel. We discuss results of randomized studies and clinical observations which have shown that pharmacokinetics of clopidogrel might vary substantially in dependence of polymorphisms of genes responsible for synthesis of P2Y12 receptors of platelets or cytochromic isoenzymes P-450 CYP of liver with participation of which formation of active metabolite of clopidogrel occurs. Contrary to practically healthy people in patients with various forms of ischemic heart disease (IHD) concomitant therapy, for instance some statins and calcium antagonists, can affect clopidogrel pharmacokinetics. Pharmacodynamics of clopidogrel in patients with IHD with acute coronary syndrome or diabetes mellitus or before percutaneous coronary interventions (PCI) also differs from that in healthy people, because in these patients hyperaggregation of platelets takes place initially and antiaggregatory action of clopidogrel is less expressed. In 10-30% of patients with IHD partial or complete resistance to antiaggregation action of clopidogrel is detected, which according to some observations is combined with elevated risk of thrombotic cardiac complications after PCI. Possible causes of resistance to clopidogrel and ways of its overcoming are discussed.

[Safety and efficacy of the use of glycoprotein IIb/IIIa inhibitors in the invasive treatment of patients with ST-elevation acute coronary syndrome].

UNLABELLED: The purpose of the study was to estimate the safety and the efficacy of the use of tirofiban, its influence on the function of the left ventricle of the heart and the clinical outcome of the patients with ST elevation acute coronary syndrome (ACS) during the rescue coronary angioplasty after the unsuccessful thrombolysis. The study included 112 patients who were randomized into two groups: in group I rescue percutaneous coronary intervention (PCI) with stenting was carried out, the patients in group 2 were administered tirofiban and rescue PCI was conducted. Analysis of the immediate events (0-30 days) showed that in the frequency (group I - 13.7%, group II - 19.2%) and intensity of bleeding there were no distinct differences between groups (p>0.05). In the tirofiban group the distinct growth in the ejection fraction LV (6+/-3% versus 3+/-5% in group I, p=0.005) was recorded. Late events (31-180 days) occurred significantly more rarely in group II (5.8% versus 21.6% in group I, p<0.05). Multivariate analysis showed that the development of cardiogenic shock (OR=6.8, 95%CI: 1.8-26, p=0.005) was an independent risk factor of prominent cardiovascular complications and events during 6 months after PCI. Thus only the use of tirofiban during PCI had a significant effect of the decrease of significant cardiovascular complications and events during 6 months after PCI (OR=0.15, 95%CI: 0.04-0.53, p=0.003). CONCLUSION: the performance of rescue PCI in combination with glycoprotein IIb/IIIa inhibitors allows to reach optimal results of the treatment of patients with ST elevation ACS after failed thrombolysis. The remote prognosis of patients after rescue PCI improves if during the intervention a patient receives IIb/IIIa inhibitors of glycoprotein receptors but at the same time considerably worsens in case of cardiogenic shock development.

[The use of tirofiban in invasive treatment of patients with non-ST-elevation acute coronary syndrome].

The study assessed 123 patients with non-ST-elevation acute coronary syndrome who were randomized into two groups: percutaneous coronary intervention (PCI) (62 patients) and PCI against background of tirofiban injection (61 patients). The results of the study were estimated during the early (up to 30 days) and the late (up to 180 days) follow-up. It was stated that the use of tirofiban has led to the increase of minor bleedings (11% versus 4.8%, p<0.05), but the total amount of bleedings between the groups did not differ: 19.7% in the tirofiban group versus 14.5% in group I. The use of tirofiban has led to the significant growth of the LV ejection fraction (5+/-4% versus 2+/-3%, p<0.05) and increment of the LV wall motion index (0.28+/-0.18 versus 0.12+/-0.21, p<0.001). There was no difference in the frequency of the early events: 9.6% versus 8.2% in the groups without and with the use of tirofiban accordingly (p<0.05). The use of tirofiban was associated with the decrease in the frequency of all events during the first 180 days after PCI: 30.7% in group I and 13.1% in the tirofiban group (p<0.005). Absence the main cardiovascular complications according to Kaplan-Meier method for all patients amounted to 77+/-6%, in the group of the patients who received tirofiban 88+/-6%, and 64+/-8% in the group of the patients who did not receive tirofiban (p=0.009). Thereby, the use of tirofiban in the treatment of the patients with non-ST-elevation acute coronary syndrome does not lead to the increase in the frequency and severity of bleedings. At the same time, the use of tirofiban in the treatment of the patients with acute coronary syndrome has a significant influence on the growth of the LV wall motion index and the LV ejection fraction by increasing them. Under these conditions when using tirofiban in the late period the frequency of all events during PCI is 2.3 times lower compared to the patients who did not receive tirofiban.