Monotherapy with a potent P2Y12 receptor antagonist after 1 month of dual antiplatelet therapy (DAPT) may reduce bleeding in the absence of increased ischaemic events compared to 12-month DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). PCI guidance with optical coherence tomography (OCT) may enhance stent expansion. COMPARE STEMI ONE is an international, multicentre, open-label, randomised controlled trial. In 1,656 ST-segment elevation myocardial infarction (STEMI) patients, prasugrel monotherapy after 1 month of DAPT, as compared to standard 12-month prasugrel-based DAPT, will be tested for non-inferiority for the primary composite endpoint of net adverse clinical events - defined as all-cause death, myocardial infarction, stroke, or Bleeding Academic Research Consortium Type 3 or 5 bleeding events - at 11 months after randomisation. Furthermore, an ancillary substudy will test the superiority of OCT-guided versus angiography-guided staged complete revascularisation in achieving a larger minimal stent area (MSA) in non-culprit lesions during staged procedures. COMPARE STEMI ONE is the first randomised controlled trial assessing an abbreviated 1-month DAPT regimen followed by prasugrel monotherapy in the context of STEMI. The trial will also study the value of OCT-guided PCI in terms of the MSA of non-culprit lesions and may elucidate potential synergies between intravascular imaging-guided PCI and abbreviated DAPT regimens. (ClinicalTrials.gov: NCT05491200).
- MeSH
- Purinergic P2Y Receptor Antagonists * therapeutic use MeSH
- ST Elevation Myocardial Infarction * therapy drug therapy diagnostic imaging surgery MeSH
- Platelet Aggregation Inhibitors * therapeutic use MeSH
- Coronary Angiography methods MeSH
- Percutaneous Coronary Intervention * methods MeSH
- Humans MeSH
- Tomography, Optical Coherence * methods MeSH
- Prasugrel Hydrochloride * therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Clinical Trial Protocol MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
OBJECTIVES: Based on previous studies with clopidogrel, the time between acute myocardial infarction (AMI) symptoms onset and primary percutaneous coronary intervention (PCI) was proven as important prognostic factor. Our aim was to assess the relationship between symptoms onset to needle time (SNT) and procedural results and the occurrence of ischemic endpoints in primary angioplasty patients treated with potent P2Y12 inhibitors. METHODS: A total of 1,131 out of 1,230 patients randomized to the Prague-18 study (prasugrel vs. ticagrelor in primary PCI) were divided into a high and a low-risk group. The effect of defined SNT on patients' ischemic endpoints and prognosis by their risk status at admission was tested. RESULTS: The median SNT was 3.2 hours. Longer SNTs resulted in a more frequent incidence of TIMI flow <3 post PCI (p=0.015). There were significant differences in the occurrence of the combined ischemic endpoint among the compared SNT groups at 30 days (p=0.032), and 1 year (p=0.011), with the highest incidence in the ≤1 h SNT group of patients. "Latecomers" (SNT>4 hs) in the high-risk group experienced more reinfarction within 1 year [OR (95% CI) 3.23 (1.09-9.62) p=0.035]; no difference was found in the low-risk group. CONCLUSIONS: In the era of intense antithrombotic medication, stratification of MI patients undergoing primary angioplasty, based on initial ischemic risk assessment affected prognosis more than symptom onset to needle time. Longer time delay was significantly related to increased incidence of ischemic events and all-cause mortality only in patients with high ischemic risk.
- MeSH
- Myocardial Infarction * MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Clopidogrel MeSH
- Percutaneous Coronary Intervention * adverse effects MeSH
- Humans MeSH
- Prasugrel Hydrochloride MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
Životní prognóza nemocných po prodělání akutního koronárního syndromu není dobrá pro definovatelné skupiny nemocných s vysokým ischemickým rizikem. Zlepšení osudu těchto pacientů je možné pomocí nejméně dvou dlouhodobých strategií kombinované antitrombotické léčby - prodlouženou duální protidestičkovou léčbu (DAPT) nebo kombinací nízké dávky rivaroxabanu s kyselinou acetylsalicylovou (Dual Pathway Inhibition, DPI). Použití těchto léčebných postupů v praxi vyžaduje pečlivé individuální posouzení rizika ischemie a rizika krvácení.
Life expectancy in the years following an acute coronary syndrome event is poor for some specific groups of patients because of their high likelihood of recurrent ischemic events. To combat this continuing risk, several clinical trials have evaluated the efficacy and safety of more intensive antithrombotic strategies - prolonged dual antiplatelet therapy (DAPT) or dual pathway inhibition approach (DPI), combining low-dose rivaroxaban and aspirin. The clinical utilization of these antithrombotic strategies requires clinicians to carefully assess the risk of recurrent ischemic and bleeding events in an individual patient.
- MeSH
- Acute Coronary Syndrome * complications MeSH
- Anticoagulants therapeutic use MeSH
- Aspirin therapeutic use MeSH
- Time Factors MeSH
- Dual Anti-Platelet Therapy MeSH
- Fibrinolytic Agents therapeutic use MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Clopidogrel therapeutic use MeSH
- Humans MeSH
- Prasugrel Hydrochloride therapeutic use MeSH
- Rivaroxaban therapeutic use MeSH
- Heart Disease Risk Factors MeSH
- Thienopyridines therapeutic use MeSH
- Ticagrelor therapeutic use MeSH
- Thrombosis * prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: The prognostic significance of periprocedural myocardial infarction (MI) remains controversial. METHODS AND RESULTS: The study aims to investigate the incidence of periprocedural MI in the era of high sensitivity diagnostic markers and intense antithrombotics, and its impact on early outcomes of patients with acute MI treated with primary angioplasty (pPCI). Data from the PRAGUE-18 (prasugrel versus ticagrelor in pPCI) study were analyzed. The primary net-clinical endpoint (EP) included death, spontaneous MI, stroke, severe bleeding, and revascularization at day 7. The key secondary efficacy EP included cardiovascular death, spontaneous MI, and stroke within 30 days. The incidence of peri-pPCI MI was 2.3% (N = 28) in 1230 study patients. The net-clinical EP occurred in 10.7% of patients with, and in 3.6% of patients without, peri-pPCI MI (HR 2.92; 95% CI 0.91-9.38; P = 0.059). The key efficacy EP was 10.7% and 3.2%, respectively (HR 3.44; 95% CI 1.06-11.13; P = 0.028). Patients with periprocedural MI were at a higher risk of spontaneous MI (HR 6.19; 95% CI 1.41-27.24; P = 0.006) and stent thrombosis (HR 10.77; 95% CI 2.29-50.70; P = 0.003) within 30 days. Age, hyperlipidemia, multi-vessel disease, post-procedural TIMI <3, pPCI on circumflex coronary artery, and periprocedural GP IIb/IIIa inhibitor were independent predictors of peri-pPCI MI. CONCLUSIONS: In the era of intense antithrombotic therapy, the occurrence of peri-pPCI MI is despite highly sensitive diagnostic markers a rare complication, and is associated with an increased risk of early reinfarction and stent thrombosis.
Cangrelor je jediným nitrožilním inhibitorem destičkového receptoru P2Y12 s klinicky prokázanou účinností pro snížení ischemických komplikací PCI. Přehledný článek popisuje jeho farmakologii, klinické studie a empirické indikace jeho použití.
Cangrelor is the only intravenous platelet P2Y12 receptor inhibitor with proven clinical efficacy for the reduction of PCI - related ischemic complications. Cangrelor pharmacology, clinical studies, and off-label indications are disscused in this review article.
- Keywords
- cangrelor,
- MeSH
- Adenosine analogs & derivatives MeSH
- Purinergic P2Y Receptor Antagonists pharmacokinetics pharmacology therapeutic use MeSH
- Dyspnea chemically induced MeSH
- Platelet Aggregation Inhibitors * pharmacokinetics pharmacology therapeutic use MeSH
- Percutaneous Coronary Intervention MeSH
- Coronary Thrombosis * prevention & control MeSH
- Humans MeSH
- Prasugrel Hydrochloride MeSH
- Ticagrelor MeSH
- Check Tag
- Humans MeSH
SAR‑REACT 5 byla multicentrická randomizovaná, otevřená studie, v níž byl pacientům s akutním koronárním syndromem (AKS), kteří byli invazivně léčeni, podáván randomizovaně tikagrelor v úvodní dávce 180 mg a dále dvakrát denně 90 mg, nebo prasugrel v úvodní dávce 60 mg a poté jednou denně 10 mg. Primární složený cílový ukazatel zahrnoval úmrtí, srdeční infarkt nebo mozkovou příhodu během jednoho roku sledování. Sekundárním cílovým ukazatelem bylo velké krvácení. U nemocných s AKS s elevacemi segmentu ST i bez nich byly zaznamenány nižší incidence úmrtí, srdečního infarktu nebo cévní mozkové příhody při léčbě prasugrelem než při léčbě tikagrelorem. Jedním z možných vysvětlení je rozdílná farmakokinetika obou přípravků.
SAR‑REACT 5 was a multicentric, randomized, open‑label study in which invasively treated patients with acute corocanry syndrome (ACS) were randomly administered with ticagrelor in an initial dose 180 mg and twice 90 mg after that or prasugrel in an initial dose 60 mg and once 10 mg after that. Primary composite endpoint included death, mycardial infarction or stroke during a one‑year follow‑up. Secondary endpoint was large bleeding. Patients with ACS with ST‑segment elevations and without them had lower incidence of death, mycoardial infarction or stroke on prasugrel compared with ticagrelor treatment. One possible explanation might be a different pharmacokinetics of both medicinal products.
- Keywords
- studie ISAR-REACT 5,
- MeSH
- Acute Coronary Syndrome * drug therapy MeSH
- Platelet Aggregation Inhibitors therapeutic use MeSH
- Humans MeSH
- Prasugrel Hydrochloride therapeutic use MeSH
- Ticagrelor therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Randomized Controlled Trial MeSH
We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity.Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles.In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018).CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity.The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.
- MeSH
- Adenosine Diphosphate metabolism MeSH
- Cytochrome P-450 CYP3A metabolism MeSH
- Cytochrome P-450 CYP2C19 metabolism MeSH
- ST Elevation Myocardial Infarction drug therapy MeSH
- Humans MeSH
- Prasugrel Hydrochloride pharmacology therapeutic use MeSH
- Ticagrelor pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Acute Coronary Syndrome * drug therapy MeSH
- Clinical Studies as Topic * MeSH
- Humans MeSH
- Prasugrel Hydrochloride therapeutic use MeSH
- Ticagrelor therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comment MeSH
Agresivní protidestičková léčba je základem terapie akutních koronárních syndromů. V akutní fázi je používána v podobě duální protidestičkové léčby (DAPT) s využitím vysoce účinných inhibitorů destičkového receptoru P2Y12. Studie ISAR-REACT 5 přímo srovnala ticagrelor a prasugrel jako součást dvou různých léčebných strategií. Výsledky studie jsou v rozporu s dosud zjištěnými skutečnostmi a jejich další interpretaci bude potřeba věnovat zvýšenou pozornost.
Aggressive antiplatelet therapy is the cornerstone for acute coronary syndrome treatment. Acute phase therapy is based on the dual antiplatelet treatment (DAPT) with highly effective inhibitors of the platelet receptor P2Y12. The ISAR-REACT 5 trial directly compare ticagrelor and prasugrel in two different antiplatelet strategies. The result of both efficacy and safety are contrary to current knowledge and needs to be carefully validated.
- Keywords
- studie ISAR REACT,
- MeSH
- Acute Coronary Syndrome * drug therapy mortality MeSH
- Purinergic P2Y Receptor Antagonists * administration & dosage adverse effects therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Hemorrhage MeSH
- Prasugrel Hydrochloride * administration & dosage adverse effects therapeutic use MeSH
- Aged MeSH
- Ticagrelor * administration & dosage adverse effects therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Aged MeSH
- Publication type
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- MeSH
- Platelet Aggregation Inhibitors pharmacology therapeutic use MeSH
- Brain Ischemia * drug therapy prevention & control MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Medication Therapy Management MeSH
- Prasugrel Hydrochloride pharmacology adverse effects therapeutic use MeSH
- Ticagrelor pharmacology adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comment MeSH
