RÉSUMÉ
AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.
Sujet(s)
Facteur-15 de croissance et de différenciation , Hémorragie , Enregistrements , Humains , Mâle , Femelle , Sujet âgé , Hémorragie/induit chimiquement , Hémorragie/épidémiologie , Hémorragie/étiologie , Adulte d'âge moyen , Facteur-15 de croissance et de différenciation/sang , Études prospectives , Maladie des artères coronaires/complications , Maladie des artères coronaires/sang , Association de médicaments , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Fibrinolytiques/administration et posologie , Fibrinolytiques/effets indésirables , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/effets indésirables , Clopidogrel/administration et posologie , Clopidogrel/effets indésirables , Pronostic , Russie/épidémiologie , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/effets indésirables , Rivaroxaban/administration et posologie , Rivaroxaban/effets indésirables , Intervention coronarienne percutanée/méthodes , Intervention coronarienne percutanée/effets indésirablesRÉSUMÉ
BACKGROUND: Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. RESEARCH DESIGN AND METHODS: A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. RESULTS: Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). CONCLUSIONS: TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.
Sujet(s)
Anticoagulants , Acide acétylsalicylique , Fibrillation auriculaire , Clopidogrel , Association de médicaments , Hémorragie , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Antagonistes des récepteurs purinergiques P2Y , Humains , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Intervention coronarienne percutanée/méthodes , Mâle , Femelle , Études rétrospectives , Sujet âgé , Adulte d'âge moyen , Hémorragie/induit chimiquement , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Acide acétylsalicylique/effets indésirables , Clopidogrel/administration et posologie , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/usage thérapeutique , Anticoagulants/administration et posologie , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Antagonistes des récepteurs purinergiques P2Y/administration et posologie , Antagonistes des récepteurs purinergiques P2Y/usage thérapeutique , Antagonistes des récepteurs purinergiques P2Y/effets indésirables , Facteurs temps , Résultat thérapeutique , Fibrinolytiques/administration et posologie , Fibrinolytiques/usage thérapeutique , Fibrinolytiques/effets indésirables , Sujet âgé de 80 ans ou plus , Ticagrélor/administration et posologie , Ticagrélor/usage thérapeutique , Ticagrélor/effets indésirablesRÉSUMÉ
Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be combined with antiplatelet agents, including aspirin and/or clopidogrel, to prevent thromboembolic diseases. This phase I trial assessed safety, pharmacokinetics, and pharmacodynamics of milvexian coadministration with aspirin and/or clopidogrel in healthy participants through 3 drug-drug interaction studies using a 3-period, 3-treatment, crossover design. A total of 113 participants were randomized to receive milvexian (200 mg; twice daily for 5 days) or matched placebo coadministered with once-daily aspirin (325 mg for 5 days) and/or clopidogrel (Day 1: 300 mg; Days 2-5: 75 mg). Milvexian was safe and well tolerated, with and without aspirin and/or clopidogrel. Eight mild bleeding adverse events (AEs) were reported in 5 of 113 participants across various treatment arms. Peak and total exposures of milvexian were similar with or without clopidogrel and/or aspirin. Exposure-dependent prolongation of activated partial thromboplastin time and reduction of FXI clotting activity by milvexian were similar with coadministration of aspirin and/or clopidogrel. Milvexian, with or without coadministration of aspirin and/or clopidogrel, did not affect bleeding time or platelet aggregation. Administration of milvexian alone or with aspirin and/or clopidogrel was safe and well tolerated without increased incidence of AEs, including bleeding. Pharmacokinetic and pharmacodynamic effects of milvexian, including bleeding time, were similar with or without aspirin and/or clopidogrel.ClinicalTrials.gov Identifier: NCT03698513.
Sujet(s)
Acide acétylsalicylique , Clopidogrel , Interactions médicamenteuses , Volontaires sains , Antiagrégants plaquettaires , Humains , Clopidogrel/pharmacocinétique , Clopidogrel/administration et posologie , Clopidogrel/effets indésirables , Acide acétylsalicylique/pharmacocinétique , Acide acétylsalicylique/administration et posologie , Mâle , Femelle , Adulte , Antiagrégants plaquettaires/pharmacocinétique , Antiagrégants plaquettaires/pharmacologie , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Adulte d'âge moyen , Études croisées , Jeune adulteRÉSUMÉ
BACKGROUND AND PURPOSE: Flow diverters with surface modifications or coatings have been recently introduced to clinical practice with the expectation that they can reduce the rate of thromboembolic complications and residual aneurysms. The purpose of this study is to evaluate the utility of the Derivo 2Heal (D2H) device, a new fibrin and heparin-coated flow diverter. MATERIALS AND METHODS: Patients treated by a single operator by using the D2H were retrospectively evaluated for demographic data, aneurysm characteristics, procedural variables, and follow-up data. All patients were treated by using a single D2H, monitored by platelet function testing and kept under single antiplatelet therapy with regular or half-dose clopidogrel or prasugrel after the procedure. RESULTS: Twenty patients with 26 aneurysms were treated. Three presented acutely with subarachnoid hemorrhage. Adjunctive devices were used in 6 patients. There were no technical failures and 2 periprocedural self-limited nonthrombotic minor adverse events. During follow-up, 1 of the acutely ruptured aneurysms reruptured, and 1 patient had a visual TIA. All patients were doing well clinically (19 with mRS of 0 and 1 with 1) at the last follow-up after discharge. The rates of total occlusion on very early angiographic (MRA/CTA or DSA, mean: 2.4 months), DSA (mean: 5.8 months), and midterm angiographic (mean: 14.5 months) follow-up for all versus uncoiled aneurysms were 68% versus 70%, 77.8% versus 90.0%, and 91.7% versus 90.1%, respectively. CONCLUSIONS: The absence of permanent neurologic deficits in the periprocedural period and favorable occlusion rates in this preliminary study suggest that the novel coating comprising fibrin and heparin may have the potential to increase the safety and efficacy of flow diversion and needs to be further studied by comparing the D2H device with its bare counterpart and other coated or surface-modified flow diverters.
Sujet(s)
Anévrysme intracrânien , Antiagrégants plaquettaires , Humains , Mâle , Femelle , Antiagrégants plaquettaires/administration et posologie , Adulte d'âge moyen , Sujet âgé , Anévrysme intracrânien/imagerie diagnostique , Anévrysme intracrânien/chirurgie , Anévrysme intracrânien/thérapie , Études rétrospectives , Résultat thérapeutique , Adulte , Héparine/administration et posologie , Endoprothèses , Clopidogrel/administration et posologie , Matériaux revêtus, biocompatiblesRÉSUMÉ
Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.
Sujet(s)
Endoprothèses à élution de substances , Bithérapie antiplaquettaire , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Insuffisance rénale chronique , Humains , Mâle , Femelle , Insuffisance rénale chronique/complications , Intervention coronarienne percutanée/méthodes , Sujet âgé , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/administration et posologie , Adulte d'âge moyen , Études prospectives , Bithérapie antiplaquettaire/méthodes , Hémorragie/épidémiologie , Hémorragie/induit chimiquement , Maladie des artères coronaires/chirurgie , Maladie des artères coronaires/complications , Facteurs temps , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologie , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Infarctus du myocarde/épidémiologie , Cause de décès/tendances , Calendrier d'administration des médicaments , Facteurs de risqueRÉSUMÉ
BACKGROUND: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency. METHODS: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95-208 PRU), and bleeding risk (< 95 PRU). RESULTS: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 - 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively. CONCLUSION: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.
Sujet(s)
Sous-famille B de transporteurs à cassette liant l'ATP , Clopidogrel , Accident vasculaire cérébral ischémique , Antiagrégants plaquettaires , Humains , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologie , Sous-famille B de transporteurs à cassette liant l'ATP/génétique , Études transversales , Mâle , Femelle , Adulte d'âge moyen , Accident vasculaire cérébral ischémique/traitement médicamenteux , Accident vasculaire cérébral ischémique/génétique , Sujet âgé , Antiagrégants plaquettaires/usage thérapeutique , Polymorphisme de nucléotide simple/génétique , Génotype , Agrégation plaquettaire/effets des médicaments et des substances chimiques , Agrégation plaquettaire/génétiqueRÉSUMÉ
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.
Sujet(s)
Clopidogrel , Infarctus du myocarde , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Ticagrélor , Humains , Clopidogrel/effets indésirables , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologie , Ticagrélor/effets indésirables , Ticagrélor/usage thérapeutique , Intervention coronarienne percutanée/effets indésirables , Intervention coronarienne percutanée/mortalité , Femelle , Mâle , Sujet âgé , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/usage thérapeutique , Adulte d'âge moyen , Résultat thérapeutique , Facteurs temps , Facteurs de risque , Infarctus du myocarde/mortalité , Maladie chronique , Antagonistes des récepteurs purinergiques P2Y/effets indésirables , Antagonistes des récepteurs purinergiques P2Y/usage thérapeutique , Nécrose , Appréciation des risques , Maladie des artères coronaires/thérapie , Maladie des artères coronaires/mortalité , Maladie des artères coronaires/imagerie diagnostique , Maladie des artères coronaires/traitement médicamenteux , Endoprothèses , Hémorragie/induit chimiquementRÉSUMÉ
The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left ventricular assist device HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) serves as bridging therapy to transplantation and/or destination therapy. Current guidelines recommend anticoagulation with a vitamin K antagonist in combination with low-dose aspirin. We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4 years because of low compatibility and a rare X-factor deficiency. This is a rare hematological disorder, estimated to affect approximately 1 in every 500,000 to 1,000,000 people in the general population. The patient finally received a modified anticoagulation regimen involving the combination of rivaroxaban and clopidogrel without warfarin. Under this regimen, the patient remained free of thromboembolic complications for 4 years with in situ placement of the left ventricular assist device. This case illustrates that under specific circumstances, long-term absence of warfarin therapy is feasible in patients with a HeartMate 3.
Sujet(s)
Anticoagulants , Dispositifs d'assistance circulatoire , Thromboembolie , Warfarine , Humains , Dispositifs d'assistance circulatoire/effets indésirables , Warfarine/usage thérapeutique , Warfarine/administration et posologie , Thromboembolie/étiologie , Thromboembolie/prévention et contrôle , Anticoagulants/usage thérapeutique , Anticoagulants/administration et posologie , Mâle , Défaillance cardiaque/chirurgie , Adulte d'âge moyen , Clopidogrel/administration et posologie , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Rivaroxaban/administration et posologie , Rivaroxaban/usage thérapeutique , Abstention thérapeutiqueRÉSUMÉ
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
Sujet(s)
Fibrillation auriculaire , Clopidogrel , Pontage aortocoronarien , Cytochrome P-450 CYP2C19 , Génotype , Antiagrégants plaquettaires , Agrégation plaquettaire , Complications postopératoires , Humains , Cytochrome P-450 CYP2C19/génétique , Cytochrome P-450 CYP2C19/métabolisme , Fibrillation auriculaire/étiologie , Fibrillation auriculaire/génétique , Fibrillation auriculaire/épidémiologie , Mâle , Femelle , Sujet âgé , Pontage aortocoronarien/effets indésirables , Adulte d'âge moyen , Clopidogrel/administration et posologie , Clopidogrel/effets indésirables , Complications postopératoires/étiologie , Complications postopératoires/épidémiologie , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/effets indésirables , Agrégation plaquettaire/effets des médicaments et des substances chimiques , Incidence , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/effets indésirablesSujet(s)
Pontage aortocoronarien , Antiagrégants plaquettaires , Humains , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Bithérapie antiplaquettaire/méthodes , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologieRÉSUMÉ
BACKGROUND: During the transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), previous studies have raised concerns about a rebound effect. We compared platelet and inflammatory cell adhesion on different types of stents in the setting of clopidogrel presence and withdrawal. METHODS: In Experiment 1, three pigs were administered with DAPT, that is, clopidogrel and acetylsalicylic acid (ASA), for 7 days. Each animal underwent an extracorporeal carotid arteriovenous shunt model implanted with fluoropolymer-coated everolimus-eluting stent (FP-EES), biodegradable-polymer sirolimus-eluting stent (BP-SES), and biodegradable-polymer everolimus-eluting stents (BP-EES). In Experiment 2, two pigs were administered DAPT, clopidogrel was then withdrawn at day 7, and SAPT with ASA was continued for next 21 days. Then flow-loop experiments with the drawn blood from each time point were performed for FP-EES, BioLinx-polymer zotarolimus-eluting stents (BL-ZES), and BP-EES. The rebound effect was defined as the statistical increase of inflammation and platelet adhesion assessed with immunohistochemistry on the stent-strut level basis from baseline to day-14 or 28. RESULTS: Both experiments showed platelet adhesion value was highest in BP-EES, while the least in FP-EES during DAPT therapy. There was no increase in platelet or inflammatory cell adhesion above baseline values (i.e., no therapy) due to the cessation of clopidogrel on the stent-strut level. Monocyte adhesion was the least for FP-EES with the same trend observed for neutrophil adhesion. CONCLUSIONS: No evidence of rebound effect was seen after the transition from DAPT to SAPT. FP-EES demonstrated the most favorable antithrombotic and anti-inflammatory profile regardless of the different experimental designs.
Sujet(s)
Acide acétylsalicylique , Clopidogrel , Endoprothèses à élution de substances , Bithérapie antiplaquettaire , Évérolimus , Adhésivité plaquettaire , Antiagrégants plaquettaires , Conception de prothèse , Sirolimus , Thrombose , Animaux , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/pharmacologie , Antiagrégants plaquettaires/effets indésirables , Clopidogrel/administration et posologie , Clopidogrel/pharmacologie , Facteurs temps , Sirolimus/analogues et dérivés , Sirolimus/administration et posologie , Sirolimus/pharmacologie , Évérolimus/administration et posologie , Évérolimus/pharmacologie , Thrombose/prévention et contrôle , Thrombose/étiologie , Acide acétylsalicylique/administration et posologie , Adhésivité plaquettaire/effets des médicaments et des substances chimiques , Anastomose chirurgicale artérioveineuse/effets indésirables , Sus scrofa , Plaquettes/effets des médicaments et des substances chimiques , Plaquettes/métabolisme , Calendrier d'administration des médicaments , Modèles animaux de maladie humaineRÉSUMÉ
BACKGROUND: Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1-3 months [short-term], 6 months [mid-term], and >12 months [extended] vs. 12 months). METHODS: We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis. RESULTS: Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02-1.28]) and bleeding (1.13 [1.00-1.28]), but not NACCE (1.12 [0.96-1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent (1.11 [1.03-1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01-2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83-1.10; and 0.96 [0.80-1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91-1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17-1.09]). CONCLUSIONS: Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI. CLINICAL TRIALS REGISTRATION: PROSPERO ID: CRD42021278663.
Sujet(s)
Bithérapie antiplaquettaire , Hémorragie , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Humains , Intervention coronarienne percutanée/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Femelle , Mâle , Bithérapie antiplaquettaire/méthodes , Hémorragie/induit chimiquement , Facteurs sexuels , Méta-analyse en réseau , Clopidogrel/administration et posologie , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.
Sujet(s)
Clopidogrel , Hémorragie gastro-intestinale , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Inhibiteurs de la pompe à protons , Humains , Clopidogrel/administration et posologie , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Intervention coronarienne percutanée/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Inhibiteurs de la pompe à protons/administration et posologie , Inhibiteurs de la pompe à protons/usage thérapeutique , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Hémorragie gastro-intestinale/induit chimiquement , Hémorragie gastro-intestinale/épidémiologie , Hémorragie gastro-intestinale/prévention et contrôle , Bithérapie antiplaquettaire/méthodes , Ésoméprazole/administration et posologie , Ésoméprazole/usage thérapeutique , Oméprazole/administration et posologie , Oméprazole/usage thérapeutique , Oméprazole/effets indésirables , Interactions médicamenteuses , Association de médicaments , Antihistaminiques des récepteurs H2/administration et posologie , Antihistaminiques des récepteurs H2/usage thérapeutiqueRÉSUMÉ
The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.
Sujet(s)
Acide acétylsalicylique , Clopidogrel , Comprimés , Clopidogrel/composition chimique , Clopidogrel/administration et posologie , Acide acétylsalicylique/composition chimique , Acide acétylsalicylique/administration et posologie , Comprimés/composition chimique , Ticlopidine/analogues et dérivés , Ticlopidine/composition chimique , Ticlopidine/administration et posologie , Association médicamenteuse , Humains , Antiagrégants plaquettaires/composition chimique , Antiagrégants plaquettaires/administration et posologie , Préparation de médicament/méthodes , Chimie pharmaceutique/méthodesRÉSUMÉ
BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).
Sujet(s)
Anticoagulants , Clopidogrel , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Antagonistes des récepteurs purinergiques P2Y , Récepteurs purinergiques P2Y12 , Ticagrélor , Humains , Intervention coronarienne percutanée/effets indésirables , Ticagrélor/effets indésirables , Ticagrélor/administration et posologie , Mâle , Études prospectives , Femelle , Sujet âgé , Adulte d'âge moyen , Clopidogrel/administration et posologie , Clopidogrel/effets indésirables , Antagonistes des récepteurs purinergiques P2Y/effets indésirables , Antagonistes des récepteurs purinergiques P2Y/administration et posologie , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/effets indésirables , Administration par voie orale , Résultat thérapeutique , Facteurs temps , Anticoagulants/administration et posologie , Anticoagulants/effets indésirables , Récepteurs purinergiques P2Y12/effets des médicaments et des substances chimiques , Récepteurs purinergiques P2Y12/sang , Tests fonctionnels plaquettaires , Agrégation plaquettaire/effets des médicaments et des substances chimiques , Phosphoprotéines/sang , Plaquettes/effets des médicaments et des substances chimiques , Plaquettes/métabolisme , Protéines des microfilaments/sang , Protéines des microfilaments/génétique , Maladie des artères coronaires/thérapie , Maladie des artères coronaires/sang , Maladie des artères coronaires/imagerie diagnostique , Molécules d'adhérence cellulaire/sang , Résistance aux substances , Bithérapie antiplaquettaire/effets indésirablesRÉSUMÉ
RATIONALE: Antiplatelet therapy (APT) is the standard of care after endovascular revascularization (EVR) in patients with peripheral artery disease (PAD). APT aims to prevent both major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nonetheless, the rates of MACE and MALE after EVR remain high. In coronary artery and cerebrovascular disease, dual APT (DAPT)compared to acetylsalicylic acid alone has been proven to reduce MACE without increasing the risk of major bleeding when applied for a restricted number of weeks. However, within the PAD population, insufficient data are available to understand the potential attributable effect of DAPT over single APT (SAPT). Therefore, prospective randomized studies in targeted study populations are warranted. TRIAL DESIGN: CLEAR-PATH is a Dutch multicenter, double-blind, placebo-controlled, randomized trial comparing SAPT (clopidogrel 75 mg plus placebo) with DAPT (clopidogrel 75 mg plus acetylsalicylic acid 80 mg) in patients with PAD undergoing EVR. CLEAR-PATH includes a time-to-event analysis with a follow-up of one year. The primary composite efficacy endpoint consists of all-cause mortality, nonfatal stroke, nonfatal myocardial infarction, severe limb ischemia, (indication for) re-intervention due to any symptomatic restenosis, re-occlusion, or due to acute limb ischemia, and major amputation. The primary safety endpoint contains major bleeding following the Thrombolysis in Myocardial Infarction classification. The enrolment started in August 2022. In total 450 primary efficacy outcome events are required which expectedly amounts to 1696 subjects. Recruitment will take approximately 36 months. CONCLUSION: CLEAR-PATH will assess the efficacy and safety of DAPT compared to SAPT following EVR in PAD patients. TRIAL REGISTRATION NUMBER: NL80009.041.21.
Sujet(s)
Acide acétylsalicylique , Clopidogrel , Bithérapie antiplaquettaire , Membre inférieur , Maladie artérielle périphérique , Antiagrégants plaquettaires , Humains , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Méthode en double aveugle , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/administration et posologie , Maladie artérielle périphérique/thérapie , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologie , Membre inférieur/vascularisation , Bithérapie antiplaquettaire/méthodes , Mâle , Angioplastie/méthodes , Thrombose/prévention et contrôle , Thrombose/étiologie , Thrombose/épidémiologie , Femelle , Pays-Bas/épidémiologie , Études prospectives , Hémorragie/induit chimiquement , Hémorragie/épidémiologieRÉSUMÉ
BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODSâANDâRESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.
Sujet(s)
Implant résorbable , Clopidogrel , Endoprothèses à élution de substances , Bithérapie antiplaquettaire , Intervention coronarienne percutanée , Antiagrégants plaquettaires , Antagonistes des récepteurs purinergiques P2Y , Enregistrements , Humains , Mâle , Sujet âgé , Femelle , Intervention coronarienne percutanée/effets indésirables , Adulte d'âge moyen , Antagonistes des récepteurs purinergiques P2Y/administration et posologie , Antagonistes des récepteurs purinergiques P2Y/effets indésirables , Antagonistes des récepteurs purinergiques P2Y/usage thérapeutique , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Clopidogrel/administration et posologie , Études prospectives , Japon , Bithérapie antiplaquettaire/méthodes , Hémorragie/induit chimiquement , Chlorhydrate de prasugrel/administration et posologie , Chlorhydrate de prasugrel/usage thérapeutique , Chlorhydrate de prasugrel/effets indésirables , Polymères , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.
Sujet(s)
Hémorragie , Accident vasculaire cérébral ischémique , Antiagrégants plaquettaires , Médecine de précision , Thromboélastographie , Humains , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Femelle , Mâle , Sujet âgé , Accident vasculaire cérébral ischémique/diagnostic , Accident vasculaire cérébral ischémique/traitement médicamenteux , Adulte d'âge moyen , Résultat thérapeutique , Facteurs de risque , Hémorragie/induit chimiquement , Valeur prédictive des tests , Résistance aux substances , Acide acétylsalicylique/effets indésirables , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Études rétrospectives , Clopidogrel/effets indésirables , Clopidogrel/administration et posologie , Clopidogrel/usage thérapeutique , Plaquettes/effets des médicaments et des substances chimiques , Prise de décision clinique , Substitution de médicament , Appréciation des risques , Sujet âgé de 80 ans ou plus , Facteurs temps , Tests fonctionnels plaquettairesRÉSUMÉ
INTRODUCTION: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. AIM: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. METHODS: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). RESULTS: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. CONCLUSION: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.
Sujet(s)
Syndrome coronarien aigu , Clopidogrel , Bithérapie antiplaquettaire , Hémorragie , Antiagrégants plaquettaires , Ticagrélor , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Syndrome coronarien aigu/mortalité , Clopidogrel/effets indésirables , Clopidogrel/usage thérapeutique , Clopidogrel/administration et posologie , Bithérapie antiplaquettaire/effets indésirables , Hémorragie/induit chimiquement , Études observationnelles comme sujet , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Appréciation des risques , Facteurs de risque , Ticagrélor/effets indésirables , Ticagrélor/usage thérapeutique , Ticagrélor/administration et posologie , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVE: Hematoma expansion (HE) predicts disability and death after acute intracerebral hemorrhage (ICH). Aspirin and anticoagulants have been associated with HE. We tested the hypothesis that P2Y12 inhibitors predict subsequent HE in patients. We explored laboratory measures of P2Y12 inhibition and dual antiplatelet therapy with aspirin (DAPT). METHODS: We prospectively identified patients with ICH. Platelet activity was measured with the VerifyNow-P2Y12 assay. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated technique. HE was defined as the difference between hematoma volumes on the initial and follow-up CT scans. Nonparametric statistics were performed with Kruskal-Wallis H, and correction for multiple comparisons performed with Dunn's test. RESULTS: In 194 patients, 15 (7.7%) were known to take a P2Y12 inhibitor (clopidogrel in all but one). Patients taking a P2Y12 inhibitor had more HE compared to patients not taking a P2Y12 inhibitor (3.5 [1.2-11.9] vs. 0.1 [-0.8-1.4] mL, p = 0.004). Patients taking DAPT experienced the most HE (7.2 [2.6-13.8] vs. 0.0 [-1.0-1.1] mL, p = 0.04). The use of P2Y12 inhibitors was associated with less P2Y12 activity (178 [149-203] vs. 288 [246-319] P2Y12 reaction units, p = 0.005). INTERPRETATION: Patients taking a P2Y12 inhibitor had more HE and less P2Y12 activity. The effect was most pronounced in patients on DAPT, suggesting a synergistic effect of P2Y12 inhibitors and aspirin with respect to HE. Acute reversal of P2Y12 inhibitors in acute ICH requires further study.