BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

• Klíčová slova
• cardiovascular outcomes, chronic coronary syndrome, clopidogrel, dual antiplatelet therapy, elective percutaneous intervention, ticagrelor,
• MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• hodnocení rizik MeSH
• infarkt myokardu * mortalita   MeSH
• inhibitory agregace trombocytů * škodlivé účinky   terapeutické užití   MeSH
• klopidogrel * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• koronární angioplastika * škodlivé účinky   mortalita   MeSH
• krvácení chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nekróza MeSH
• nemoci koronárních tepen terapie   mortalita   diagnostické zobrazování   farmakoterapie   MeSH
• purinergní receptory P2Y - antagonisté škodlivé účinky   terapeutické užití   MeSH
• rizikové faktory MeSH
• senioři MeSH
• stenty MeSH
• ticagrelor * škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• inhibitory agregace trombocytů * MeSH
• klopidogrel * MeSH
• purinergní receptory P2Y - antagonisté MeSH
• ticagrelor * MeSH

The introduction of percutaneous coronary intervention (PCI) substantially changed the treatment of patients with coronary artery disease. Stent thrombosis is the most worrisome early complication in patients undergoing PCI. Therefore, antiplatelet therapy forms an integral component of treatment with intracoronary stent implantation. A multitude of randomized and observational studies have helped identify and define the role of clopidogrel in today's PCI patient. Although much is known about its use, a number of questions still remain.

• MeSH
• balónková koronární angioplastika * škodlivé účinky   MeSH
• elektivní chirurgické výkony * MeSH
• klopidogrel MeSH
• lidé MeSH
• nemoci koronárních tepen farmakoterapie   chirurgie   MeSH
• pooperační komplikace etiologie   prevence a kontrola   MeSH
• předoperační péče * metody   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• tiklopidin analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• klopidogrel MeSH
• tiklopidin MeSH

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

• MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   MeSH
• aplikace orální MeSH
• incidence MeSH
• inhibitory agregace trombocytů škodlivé účinky   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci epidemiologie   mortalita   MeSH
• klopidogrel škodlivé účinky   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• krvácení chemicky indukované   epidemiologie   MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antikoagulancia MeSH
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH

The aim of this study was to analyze periprocedural and mid-term effect of clopidogrel on platelet function using the VerifyNow P2Y12 point-of-care assay in patients undergoing TAVI. Platelet reactivity was measured at the beginning of the procedure after 300 mg clopidogrel bolus administration and during the follow-up (at 1 month after the procedure) in 52 patients undergoing TAVI using the Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU was used to identify nonresponders to clopidogrel treatment with high residual platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and in 72% of patients during 6-month follow-up. There was no significant difference in the pharmacodynamic effects of clopidogrel on platelet reactivity from baseline to 6-months follow-up (297 ± 57 vs. 275 ± 62; P = 0.058). Ischemic event occurred only in 3 patients (5.8%) from the study group. In conclusion, majority of patients undergoing TAVI had high residual platelet reactivity after pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI population raises the question of the routine use of dual antiplatelet treatment in this setting.

• MeSH
• aktivace trombocytů * MeSH
• akutní koronární syndrom patologie   chirurgie   MeSH
• aortální chlopeň patologie   chirurgie   MeSH
• cévní protézy * MeSH
• infarkt myokardu patologie   chirurgie   MeSH
• klopidogrel MeSH
• lidé MeSH
• následné studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tiklopidin analogy a deriváty   terapeutické užití   MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• klopidogrel MeSH
• tiklopidin MeSH

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

• MeSH
• aplikace orální MeSH
• Aspirin škodlivé účinky   terapeutické užití   MeSH
• incidence MeSH
• inhibitory agregace trombocytů škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci epidemiologie   mortalita   MeSH
• klopidogrel škodlivé účinky   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• krvácení chemicky indukované   epidemiologie   MeSH
• lidé MeSH
• pooperační období MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * MeSH
• trombóza epidemiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• Aspirin MeSH
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH

CONTEXT: Ticagrelor, a novel, reversible, and oral P2Y12 receptor antagonist, was claimed to reduce all-cause mortality compared to clopidogrel in the PLATO trial. OBJECTIVE: We sought to ascertain vital status follow-up for clopidogrel and ticagrelor to determine if any discrepancy existed by reviewing data from the FDA Complete Response Review. RESULTS: The FDA Complete Response Review indicated misrepresentation of vital status follow-up by the sponsor's presenter at the Cardiovascular and Renal Drugs Advisory Committee. Instead of five patients with missing vital status follow-up, the FDA primary efficacy reviewer indicated that there was a minimum of 106 patients. Additionally and more concerning was the fact that significantly more patients on ticagrelor (3.1%, n = 289 patients) had incomplete vital status follow-up versus clopidogrel (2.6%, n = 242 patients, p = 0.04 for the difference). CONCLUSIONS: The Advisory Committee that voted in favor to approve ticagrelor was given misrepresented data, which may have affected the approval of ticagrelor. The fact that significantly more patients on ticagrelor had incomplete vital status follow-up versus clopidogrel challenges the claimed mortality benefit of ticagrelor and the approval of the PLATO trial.

• Klíčová slova
• Clopidogrel, Misrepresentations, Ticagrelor,
• MeSH
• adenosin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• hodnocení rizik MeSH
• klinické zkoušky jako téma etika   normy   MeSH
• klopidogrel MeSH
• kontraindikace MeSH
• lidé MeSH
• mortalita trendy   MeSH
• následné studie MeSH
• poradní výbory normy   MeSH
• purinergní receptory P2Y - antagonisté terapeutické užití   MeSH
• schvalování léčiv * MeSH
• statistika přirozeného pohybu MeSH
• ticagrelor MeSH
• tiklopidin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• adenosin MeSH
• klopidogrel MeSH
• purinergní receptory P2Y - antagonisté MeSH
• ticagrelor MeSH
• tiklopidin MeSH

BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.

• Klíčová slova
• chronic coronary syndrome, complex percutaneous coronary intervention, coronary artery disease, myocardial infarction, ticagrelor,
• MeSH
• akutní koronární syndrom * diagnostické zobrazování   terapie   komplikace   MeSH
• infarkt myokardu * etiologie   MeSH
• inhibitory agregace trombocytů škodlivé účinky   terapeutické užití   MeSH
• klopidogrel škodlivé účinky   terapeutické užití   MeSH
• koronární angioplastika * škodlivé účinky   MeSH
• lidé MeSH
• ticagrelor škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH
• ticagrelor MeSH

Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

• Klíčová slova
• Cardiac arrest, Clopidogrel, Hypothermia, Myocardial infarction, Prasugrel, Ticagrelor,
• MeSH
• adenosin aplikace a dávkování   analogy a deriváty   MeSH
• infarkt myokardu komplikace   terapie   MeSH
• klopidogrel MeSH
• lidé středního věku MeSH
• lidé MeSH
• prasugrel hydrochlorid aplikace a dávkování   MeSH
• prospektivní studie MeSH
• purinergní receptory P2Y - agonisté aplikace a dávkování   MeSH
• senioři MeSH
• srdeční zástava etiologie   terapie   MeSH
• terapeutická hypotermie metody   MeSH
• ticagrelor MeSH
• tiklopidin aplikace a dávkování   analogy a deriváty   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adenosin MeSH
• klopidogrel MeSH
• prasugrel hydrochlorid MeSH
• purinergní receptory P2Y - agonisté MeSH
• ticagrelor MeSH
• tiklopidin MeSH

OBJECTIVE: The purpose of the present study was to investigate the association between left ventricular systolic function and the response to clopidogrel. METHODS: The efficacy of clopidogrel was measured by the vasodilator-stimulated phosphoprotein phosphorylation 20 ± 4 h after 600 mg of clopidogrel. High on-clopidogrel platelet reactivity (HCPR) was defined as a platelet reactivity index (PRI) ≥50%. The 30-day combined incidence of death, non-fatal acute coronary syndrome, re-percutaneous coronary intervention (PCI), stent thrombosis, and stroke was also investigated. RESULTS: The study group consisted of 519 patients undergoing PCI. The values (mean and 95% confidence interval) of the PRI were as follows: 40.4% (37.8-43.0) in patients with left ventricular ejection fraction (LVEF) >50%, 42.4% (39.3-45.6) in patients with LVEF 35-50%, and 46.7% (40.6-52.9) in patients with LVEF <35% (p = 0.013). The proportions of patients with HCPR were 35.9% in patients with LVEF ≥35 and 51.9% in patients with LVEF <35% (p = 0.022). After adjustment for variables that significantly influenced clopidogrel efficacy, LVEF <35% was found to be independently associated with HCPR (p = 0.039). The 30-day combined clinical endpoint occurred in 18% of patients with LVEF <35% and in 7.3% of patients with LVEF ≥35% (p = 0.026). The 30-day incidence of all-cause mortality was 14% in patients with LVEF <35 and 1.0% in patients with LVEF ≥35% (p < 0.001). CONCLUSION: An LVEF <35% was found to be independently associated with HCPR.

• MeSH
• akutní koronární syndrom epidemiologie   MeSH
• cévní mozková příhoda epidemiologie   MeSH
• dysfunkce levé srdeční komory farmakoterapie   epidemiologie   patofyziologie   MeSH
• fosfoproteiny metabolismus   MeSH
• inhibitory agregace trombocytů farmakologie   terapeutické užití   MeSH
• klopidogrel MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrofilamentové proteiny metabolismus   MeSH
• molekuly buněčné adheze metabolismus   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stenty MeSH
• tepový objem MeSH
• tiklopidin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfoproteiny MeSH
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH
• mikrofilamentové proteiny MeSH
• molekuly buněčné adheze MeSH
• tiklopidin MeSH
• Vasodilator-Stimulated Phosphoprotein MeSH

AIMS: In the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38), prasugrel reduced the primary ischaemic endpoint as compared with clopidogrel in acute coronary syndrome (ACS) patients planned to undergo percutaneous coronary interventions, but increased the risk of bleeding. The present analysis shows the efficacy and safety data for the 10,074 non-ST segment elevation (NSTE)-ACS patients included in that trial. METHODS AND RESULTS: The primary endpoint was significantly reduced by prasugrel in the overall NSTE-ACS population (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.73-0.93, p=0.002) as well as in unstable angina (UA) and in non-ST elevation myocardial infarction (NSTEMI) patient subgroups (interaction p value=0.39). Although non-coronary artery bypass graft (CABG) TIMI major bleeding was increased with prasugrel as compared with clopidogrel (HR 1.40, 95% CI 1.05-1.88, p=0.02), there was a net clinical benefit in patients assigned to prasugrel (HR 0.89, 95% CI 0.80-1.00, p=0.043), which was consistent for UA and NSTEMI subgroups (interaction p value=0.84 and 0.72). In patients who met the criteria for prasugrel use recommended by the European Medicines Agency, thus excluding from the analysis patients with prior transient ischemic attack (TIA)/stroke, with weight <60 kg or age ≥75 years, and censoring follow-up at 365 days, (European Union (EU)-label cohort) prasugrel showed superiority over clopidogrel with regard to the primary endpoint (HR 0.73, 95% CI 0.63-0.85, p<0.0001) for the entire NSTE-ACS population, as well as for UA patients and NSTEMI patients without significant differences in non-CABG TIMI major bleeding. CONCLUSION: Prasugrel, as compared with clopidogrel, significantly reduced the primary endpoint of the TRITON-TIMI 38 trial in NSTE-ACS patients, as well as in the UA and NSTEMI groups. A significant reduction in the primary endpoint without increased bleeding was observed in the EU-label cohort.

• Klíčová slova
• Acute coronary syndrome, clopidogrel, percutaneous coronary intervention, prasugrel,
• MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu farmakoterapie   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• klopidogrel MeSH
• krvácení chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nestabilní angina pectoris farmakoterapie   MeSH
• piperaziny terapeutické užití   MeSH
• prasugrel hydrochlorid MeSH
• rizikové faktory MeSH
• thiofeny terapeutické užití   MeSH
• tiklopidin analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH
• piperaziny MeSH
• prasugrel hydrochlorid MeSH
• thiofeny MeSH
• tiklopidin MeSH