BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.
- MeSH
- Purinergic P2Y Receptor Antagonists therapeutic use MeSH
- Myocardial Infarction etiology prevention & control MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Clopidogrel therapeutic use MeSH
- Coronary Angiography MeSH
- Percutaneous Coronary Intervention adverse effects MeSH
- Coronary Disease therapy MeSH
- Humans MeSH
- Aged MeSH
- Ticlopidine therapeutic use MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Clinical Trial Protocol MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
Článek navazuje na předchozí sdělení tématu tohoto čísla časopisu o ischemických cévních mozkových příhodách (iCMP). Podává přehled o antiagregačních a antikoagulačních lécích, které jsou základem sekundární prevence iCMP. Zaměřuje se na specifika i nežádoucí účinky jednotlivých léků, na výběr vhodné terapie s ohledem na etiologii iCMP a zmiňuje i některé méně časté klinické situace.
This article is related to previous articles in this issue discussing ischemic stroke. It provides an overview of antiplatelet and anticoagulation therapy that is a crucial part of stroke secondary prevention. The article focuses on specifics and side-effects of each single medication, on choosing appropriate therapy according to the stroke etiology and it also mentions some less common clinical situations
- MeSH
- Anticoagulants pharmacology adverse effects MeSH
- Antithrombins adverse effects therapeutic use MeSH
- Aspirin administration & dosage MeSH
- Stroke * epidemiology drug therapy prevention & control MeSH
- Renal Insufficiency, Chronic drug therapy complications MeSH
- Risk Assessment MeSH
- Platelet Aggregation Inhibitors pharmacology therapeutic use MeSH
- Clopidogrel administration & dosage adverse effects MeSH
- Hemorrhage epidemiology chemically induced prevention & control MeSH
- Drug Resistance MeSH
- Humans MeSH
- Secondary Prevention methods MeSH
- Ticlopidine administration & dosage pharmacology adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Variable response after clopidogrel is well documented and may affect major adverse clinical events after stroke. Impact of CYP2C19 genetic polymorphisms is an established marker linked to variable response after clopidogrel. However, the association of certain genetic polymorphisms with prediction of major adverse clinical events following stroke still remains controversial, especially in Caucasians. STUDY QUESTION: The primary aim was to evaluate the impact of CYP2C19 allele *2 in heterozygote form on major adverse clinical events in Caucasian poststroke survivors treated with clopidogrel. The secondary aim was to analyze the potential link between CYP2C19 genetic polymorphism and variable response after clopidogrel. STUDY DESIGN: One hundred thirty patients of Caucasian origin following documented ischemic stroke were included. Platelet reactivity was assessed by light transmittance aggregometry (LTA) and matched with various CYP2C19 loss-of-function genetic polymorphisms and major adverse clinical events (composite of vascular deaths, stroke/transient ischemic attack, and myocardial infarction). RESULTS: Over the mean follow-up of 14.9 months, 19 patients experienced major adverse clinical events. The risk of major adverse clinical events was nearly 3-fold in loss-of-function allele carriers (hazard ratio = 2.904; 95% confidence interval, 1.083-7.786; P = 0.013), whereas the risk of ischemic stroke or transient ischemic attack alone was also higher (hazard ratio = 3.170; 95% confidence interval, 1.281-7.849; P = 0.034). Platelet activity was strongly associated with allele *2 status (rs = 0.21, P = 0.016) but not with other genetic polymorphisms. Carriers of allele*2 exhibited lower platelet response to adenosine diphosphate-mean LTA (30.1% vs. 42.0%; P = 0.017). There were no significant differences in LTA results with other agonists. Strong association of increase in adenosine diphosphate-induced aggregation with diabetes mellitus (rs = 0.20, P = 0.023), increasing age (rs = 0.23, P = 0.008), and conversely diminishing over increased weight (rs = 0.23, P = 0.009) was also detected. The carriers of other gene allele variants lack uniformed impact on variable response after clopidogrel. CONCLUSIONS: Even heterozygous CYP2C19*2 allele carriers among Caucasian patients after ischemic stroke had a higher risk of major adverse clinical events. The LTA, however, did not predict major adverse clinical events. The exact clinical utility of these findings is still uncertain and requires large outcome-driven randomized trial in Caucasians for proof of concept.
- MeSH
- Platelet Aggregation drug effects MeSH
- White People genetics statistics & numerical data MeSH
- Biomarkers analysis MeSH
- Stroke complications drug therapy genetics MeSH
- Cytochrome P-450 CYP2C19 genetics MeSH
- Genotype MeSH
- Heterozygote MeSH
- Risk Assessment MeSH
- Myocardial Infarction epidemiology etiology genetics prevention & control MeSH
- Platelet Aggregation Inhibitors pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Loss of Function Mutation MeSH
- Polymorphism, Genetic MeSH
- Survivors statistics & numerical data MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Ticlopidine analogs & derivatives pharmacology therapeutic use MeSH
- Ischemic Attack, Transient epidemiology etiology genetics prevention & control MeSH
- Age Factors MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Keywords
- protidestičkové léky,
- MeSH
- Aspirin administration & dosage therapeutic use MeSH
- Stroke prevention & control MeSH
- Fibrinolytic Agents MeSH
- Proton Pump Inhibitors adverse effects MeSH
- Myocardial Ischemia prevention & control MeSH
- Clopidogrel MeSH
- Drug Therapy, Combination MeSH
- Hemorrhage chemically induced MeSH
- Humans MeSH
- Practice Guidelines as Topic MeSH
- Ticlopidine analogs & derivatives antagonists & inhibitors therapeutic use MeSH
- Thrombosis * prevention & control MeSH
- Check Tag
- Humans MeSH
- MeSH
- Purinergic P2Y Receptor Antagonists administration & dosage MeSH
- Anticoagulants administration & dosage MeSH
- Aspirin administration & dosage MeSH
- Time-to-Treatment standards MeSH
- Dyslipidemias diagnosis drug therapy MeSH
- Atrial Fibrillation drug therapy MeSH
- Hydroxymethylglutaryl CoA Reductases administration & dosage MeSH
- ST Elevation Myocardial Infarction * diagnostic imaging drug therapy surgery MeSH
- Percutaneous Coronary Intervention methods MeSH
- Cholesterol, LDL analysis drug effects MeSH
- Humans MeSH
- Nitroglycerin administration & dosage MeSH
- Drug-Eluting Stents MeSH
- Ticlopidine administration & dosage MeSH
- Thrombolytic Therapy methods MeSH
- Emergency Medical Services MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline MeSH
- MeSH
- Acute Coronary Syndrome * drug therapy complications prevention & control MeSH
- Purinergic P2Y Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Anticoagulants administration & dosage adverse effects therapeutic use MeSH
- European Union MeSH
- ST Elevation Myocardial Infarction diagnosis drug therapy MeSH
- Platelet Aggregation Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Myocardial Ischemia diagnosis drug therapy prevention & control MeSH
- Percutaneous Coronary Intervention * methods trends utilization MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Prasugrel Hydrochloride administration & dosage adverse effects therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Practice Guidelines as Topic MeSH
- Statistics as Topic MeSH
- Ticlopidine antagonists & inhibitors adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
Prudký rozvoj antitrombotické léčby významně přispěl ke zlepšení péče o pacienty s ischemickou chorobou srdeční a rozvoji intervenční kardiologie a dalších oborů zabývajících se kardiovaskulární problematikou. Práce je věnována aktuálním poznatkům v individualizaci léčby na podkladě rizikové stratifikace pacientů a léčebné strategie včetně aktuálních léčebných algoritmů pro indikaci a trvání duální protidestičkové léčby i její kombinaci s orální antikoagulační terapií.
Rapid development of antithrombotic treatment has significantly improved the quality of care of patients with ischemic heartdisease as well as contributed to the development of cardiovascular medicine and interventional cardiology, in particular. In thispaper, individualized therapy based on risk stratifications, treatment strategy, algorithms for dual antiplatelet therapy and itscombination with oral anticoagulation will be discussed.
- MeSH
- Purinergic P2Y Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Anticoagulants administration & dosage adverse effects therapeutic use MeSH
- Administration, Oral MeSH
- Aspirin administration & dosage adverse effects therapeutic use MeSH
- Platelet Aggregation Inhibitors * administration & dosage adverse effects therapeutic use MeSH
- Drug Therapy, Combination methods trends utilization MeSH
- Percutaneous Coronary Intervention * methods trends utilization MeSH
- Hemorrhage prevention & control therapy MeSH
- Humans MeSH
- Prasugrel Hydrochloride administration & dosage adverse effects therapeutic use MeSH
- Statistics as Topic MeSH
- Drug-Eluting Stents * adverse effects trends utilization MeSH
- Ticlopidine administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Dabigatran etexilát má své pevné místo v prevenci cévní mozkové příhody u nemocných s fibrilací síní i v léčbě a zejména v sekundární prevenci žilního tromboembolismu. V roce 2017 byly publikovány studie, které ověřily nové možnosti antikoagulačního zajištění pacientů podstupujících katetrizační ablaci fibrilace síní a antitrombotického zajištění pacientů s fibrilací síní podstupujících perkutánní koronární intervenci. Ve studii RE‑CIRCUIT vedla léčba dabigatranem k významně nižšímu výskytu krvácivých příhod ve srovnání s warfarinem v osmitýdenním období po katetrizační ablaci. Ve studii RE‑DUAL PCI byla pak prokázána vyšší bezpečnost dvojkombinace inhibitoru P2Y12 a obou dávek dabigatranu oproti standardní triple terapii s warfarinem.
Dabigatran etexilate has its firm place in the prevention of stroke in patients with atrial fibrillation and in therapy, and in particular, in secondary prevention of venous thromboembolism. Studies published in 2017 determined new options for anticoagulation approaches in patients with atrial fibrillation undergoing catheter ablation and percutaneous coronary intervention. In RE‑CIRCUIT study, therapy with dabigatran lead to significantly lower incidence of haemorrhagic events in compared with warfarin in eight‑week interval after catheter ablation. In RE‑DUAL PCI study, increased safety of dual combination of P2Y12 inhibitors and both doses of dabigatran compared with standard triple therapy with warfarin was observed.
- MeSH
- Purinergic P2Y Receptor Antagonists administration & dosage adverse effects therapeutic use MeSH
- Anticoagulants pharmacokinetics adverse effects therapeutic use MeSH
- Aspirin administration & dosage adverse effects therapeutic use MeSH
- Stroke drug therapy complications prevention & control MeSH
- Dabigatran * administration & dosage adverse effects therapeutic use MeSH
- Atrial Fibrillation drug therapy complications prevention & control MeSH
- Drug Evaluation * MeSH
- Catheter Ablation methods adverse effects MeSH
- Drug Therapy, Combination * methods utilization MeSH
- Percutaneous Coronary Intervention methods adverse effects MeSH
- Hemorrhage drug therapy complications prevention & control MeSH
- Humans MeSH
- Randomized Controlled Trials as Topic MeSH
- Practice Guidelines as Topic MeSH
- Statistics as Topic MeSH
- Ticlopidine administration & dosage adverse effects therapeutic use MeSH
- Thromboembolism drug therapy prevention & control MeSH
- Warfarin administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- MeSH
- Acute Coronary Syndrome * surgery prevention & control MeSH
- Aspirin administration & dosage adverse effects MeSH
- Time-to-Treatment MeSH
- Renal Insufficiency, Chronic epidemiology drug therapy MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Drug Substitution MeSH
- Cytochrome P450 Family 12 antagonists & inhibitors administration & dosage pharmacology MeSH
- Secondary Prevention MeSH
- Ticlopidine analogs & derivatives administration & dosage pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
