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

PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of extra bleeding. Following approval of CT and LT for long-term secondary prevention indication, recent FDA review verified some bleeding outcomes in PEGASUS. To compare the risks after CT and LT against placebo by seven TIMI scale variables, and 9 bleeding categories considered as serious adverse events (SAE) in light of PEGASUS drug discontinuation rates (DDR). The DDR in all PEGASUS arms was high reaching astronomical 32% for CT. The distribution of some outcomes (TIMI major, trauma, epistaxis, iron deficiency, hemoptysis, and anemia) was reasonable. However, the TIMI minor events were heavily underreported when compared to similar trials. Other bleedings (intracranial, spontaneous, hematuria, and gastrointestinal) appear sporadic, lacking expected dose-dependent impact of CT and LT. Few SAE outcomes (fatal, ecchymosis, hematoma, bruises, bleeding) paradoxically reported more bleeding after LT than after CT. Many bleeding outcomes were probably missed in PEGASUS potentially due to massive non-compliance, information censoring, or both. The FDA must improve reporting of trial outcomes especially in the sponsor-controlled environment when DDR and incomplete follow-up rates are high.

• Klíčová slova
• Adverse events, Aspirin, Bleeding, Clinical trial, Non-compliance, Ticagrelor, Trial conduct,
• MeSH
• adenosin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• cenzura ve výzkumu MeSH
• infarkt myokardu farmakoterapie   MeSH
• krvácení chemicky indukované   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• rozvrh dávkování léků MeSH
• ticagrelor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH
• Názvy látek
• adenosin MeSH
• ticagrelor MeSH

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

BACKGROUND: In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. METHODS: Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. RESULTS: Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). CONCLUSIONS: High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

• Klíčová slova
• hemorrhagic stroke, ischemic stroke, platelet aggregation inhibitors, secondary prevention, stroke, thrombosis, ticagrelor,
• MeSH
• adenosin aplikace a dávkování   analogy a deriváty   terapeutické užití   MeSH
• Aspirin aplikace a dávkování   terapeutické užití   MeSH
• cévní mozková příhoda farmakoterapie   prevence a kontrola   MeSH
• infarkt myokardu farmakoterapie   prevence a kontrola   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• intrakraniální krvácení prevence a kontrola   MeSH
• krvácení chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen farmakoterapie   MeSH
• purinergní receptory P2Y - antagonisté terapeutické užití   MeSH
• riziko MeSH
• sekundární prevence metody   MeSH
• senioři MeSH
• ticagrelor MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adenosin MeSH
• Aspirin MeSH
• inhibitory agregace trombocytů MeSH
• purinergní receptory P2Y - antagonisté MeSH
• ticagrelor MeSH

AIMS: PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. METHODS AND RESULTS: This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). CONCLUSION: Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. CLINICALTRIALS.GOV IDENTIFIER: NCT01225562.

• Klíčová slova
• Antiplatelet drugs, Dual antiplatelet therapy, Medically managed, Myocardial infarction, Ticagrelor,
• MeSH
• adenosin terapeutické užití   MeSH
• infarkt myokardu * farmakoterapie   prevence a kontrola   MeSH
• inhibitory agregace trombocytů škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• purinergní receptory P2Y - antagonisté * terapeutické užití   MeSH
• sekundární prevence MeSH
• ticagrelor terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adenosin MeSH
• inhibitory agregace trombocytů MeSH
• purinergní receptory P2Y - antagonisté * MeSH
• ticagrelor MeSH

BACKGROUND: Early outcomes of patients in the PRAGUE-18 (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction) study did not find any significant differences between 2 potent P2Y12 inhibitors. OBJECTIVES: The 1-year follow-up of the PRAGUE-18 study focused on: 1) a comparison of efficacy and safety between prasugrel and ticagrelor; and 2) the risk of major ischemic events related to an economically motivated post-discharge switch to clopidogrel. METHODS: A total of 1,230 patients with acute myocardial infarction (MI) treated with primary percutaneous coronary intervention were randomized to prasugrel or ticagrelor with an intended treatment duration of 12 months. The combined endpoint was cardiovascular death, MI, or stroke at 1 year. Because patients had to cover the costs of study medication after hospital discharge, some patients decided to switch to clopidogrel. RESULTS: The endpoint occurred in 6.6% of prasugrel patients and in 5.7% of ticagrelor patients (hazard ratio: 1.167; 95% confidence interval: 0.742 to 1.835; p = 0.503). No significant differences were found in: cardiovascular death (3.3% vs. 3.0%; p = 0.769), MI (3.0% vs. 2.5%; p = 0.611), stroke (1.1% vs. 0.7%; p = 0.423), all-cause death (4.7% vs. 4.2%; p = 0.654), definite stent thrombosis (1.1% vs. 1.5%; p = 0.535), all bleeding (10.9% vs. 11.1%; p = 0.999), and TIMI (Thrombolysis In Myocardial Infarction) major bleeding (0.9% vs. 0.7%; p = 0.754). The percentage of patients who switched to clopidogrel for economic reasons was 34.1% (n = 216) for prasugrel and 44.4% (n = 265) for ticagrelor (p = 0.003). Patients who were economically motivated to switch to clopidogrel had (compared with patients who continued the study medications) a lower risk of major cardiovascular events; however, they also had lower ischemic risk. CONCLUSIONS: Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767).

• Klíčová slova
• myocardial infarction, outcome, prasugrel, primary percutaneous coronary intervention, switch, ticagrelor,
• MeSH
• časové faktory MeSH
• infarkt myokardu diagnóza   mortalita   terapie   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• klopidogrel terapeutické užití   MeSH
• koronární angioplastika * MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prasugrel hydrochlorid terapeutické užití   MeSH
• senioři MeSH
• ticagrelor terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři 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
• prasugrel hydrochlorid MeSH
• ticagrelor MeSH

BACKGROUND: No randomized head-to-head comparison of the efficacy and safety of ticagrelor and prasugrel has been published in the 7 years since the higher efficacy of these newer P2Y12 inhibitors were first demonstrated relative to clopidogrel. METHODS: This academic study was designed to compare the efficacy and safety of prasugrel and ticagrelor in acute myocardial infarction treated with primary or immediate percutaneous coronary intervention. A total of 1230 patients were randomly assigned across 14 sites to either prasugrel or ticagrelor, which was initiated before percutaneous coronary intervention. Nearly 4% were in cardiogenic shock, and 5.2% were on mechanical ventilation. The primary end point was defined as death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the in-hospital phase). This analysis presents data from the first 30 days (key secondary end point). The total follow-up will be 1 year for all patients and will be completed in 2017. RESULTS: The study was prematurely terminated for futility. The occurrence of the primary end point did not differ between groups receiving prasugrel and ticagrelor (4.0% and 4.1%, respectively; odds ratio, 0.98; 95% confidence interval, 0.55-1.73; P=0.939). No significant difference was found in any of the components of the primary end point. The occurrence of key secondary end point within 30 days, composed of cardiovascular death, nonfatal myocardial infarction, or stroke, did not show any significant difference between prasugrel and ticagrelor (2.7% and 2.5%, respectively; odds ratio, 1.06; 95% confidence interval, 0.53-2.15; P=0.864). CONCLUSIONS: This head-to-head comparison of prasugrel and ticagrelor does not support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction treated with a primary percutaneous coronary intervention strategy. The observed rates of major outcomes were similar but with broad confidence intervals around the estimates. These interesting observations need to be confirmed in a larger trial. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02808767.

• Klíčová slova
• myocardial infarction, percutaneous coronary intervention, prasugrel hydrochloride, safety, ticagrelor, treatment outcome,
• MeSH
• adenosin aplikace a dávkování   analogy a deriváty   terapeutické užití   MeSH
• dospělí MeSH
• infarkt myokardu farmakoterapie   patologie   terapie   MeSH
• inhibitory agregace trombocytů aplikace a dávkování   terapeutické užití   MeSH
• koronární angioplastika metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prasugrel hydrochlorid aplikace a dávkování   terapeutické užití   MeSH
• senioři MeSH
• ticagrelor MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adenosin MeSH
• inhibitory agregace trombocytů MeSH
• prasugrel hydrochlorid MeSH
• ticagrelor MeSH

OBJECTIVE: Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. METHODS: We examined information from the FDA complete response review. RESULTS: FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p = 0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p = 0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR = 1.21, 95% CI: 0.91 to 1.59, p = 0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p < 0.0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p = 0.002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to "softer" endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor. DISCUSSION: The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality.

• Klíčová slova
• Acute coronary syndrome, Clopidogrel, Myocardial infarction, Ticagrelor,
• MeSH
• adenosin analogy a deriváty   terapeutické užití   MeSH
• akutní koronární syndrom diagnóza   farmakoterapie   epidemiologie   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• lidé MeSH
• purinergní receptory P2Y - antagonisté terapeutické užití   MeSH
• reprodukovatelnost výsledků MeSH
• stanovení cílového parametru metody   normy   MeSH
• ticagrelor MeSH
• Úřad Spojených států pro potraviny a léky normy   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Spojené státy americké MeSH
• Názvy látek
• adenosin MeSH
• inhibitory agregace trombocytů MeSH
• purinergní receptory P2Y - antagonisté MeSH
• ticagrelor 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.

• Klíčová slova
• ADP test, Cytochrome P450, aggregation, lansoprazole, prasugrel, ticagrelor,
• MeSH
• adenosindifosfát metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• cytochrom P450 CYP2C19 metabolismus   MeSH
• infarkt myokardu s elevacemi ST úseků farmakoterapie   MeSH
• lidé MeSH
• prasugrel hydrochlorid farmakologie   terapeutické užití   MeSH
• ticagrelor farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosindifosfát MeSH
• CYP2C19 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• cytochrom P450 CYP2C19 MeSH
• prasugrel hydrochlorid MeSH
• ticagrelor MeSH

The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3-3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7-3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and especially in TRACER. In conclusion, data from clinical trials, their sub-studies and affiliated FDA reviews indicate that RI cause more vascular occlusions and bleeding in ACS patients treated with DAPT. Among the novel antiplatelet agents, prasugrel and vorapaxar, but probably not ticagrelor, offer advantage in RI patients.

• Klíčová slova
• clinical trials, clopidogrel, creatinine clearance, drug safety, prasugrel, renal function, ticagrelor, vorapaxar,
• MeSH
• adenosin analogy a deriváty   farmakologie   MeSH
• akutní koronární syndrom * komplikace   farmakoterapie   MeSH
• hodnoty glomerulární filtrace MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• klinické zkoušky jako téma MeSH
• klopidogrel MeSH
• krvácení chemicky indukované   prevence a kontrola   MeSH
• laktony farmakologie   MeSH
• lidé MeSH
• prasugrel hydrochlorid farmakologie   MeSH
• pyridiny farmakologie   MeSH
• renální insuficience * komplikace   diagnóza   MeSH
• srovnávací výzkum účinnosti MeSH
• ticagrelor MeSH
• tiklopidin analogy a deriváty   farmakologie   MeSH
• výběr pacientů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adenosin MeSH
• inhibitory agregace trombocytů MeSH
• klopidogrel MeSH
• laktony MeSH
• prasugrel hydrochlorid MeSH
• pyridiny MeSH
• ticagrelor MeSH
• tiklopidin MeSH
• vorapaxar MeSH Prohlížeč