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1.
Bioorg Med Chem Lett ; 72: 128872, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35777717

RESUMO

The serendipitous prodrug clopidogrel (CPG, M0) is the mainstay antiplatelet drug in clinical use. The thiophene moiety of CPG undergoes ring opening to form the active metabolite (M13) through two steps of cytochrome P450 (CYP)-catalyzed oxidation. The stable intermediate resulting from the first oxidation, 2-oxo-CPG (M2), is proposed to be oxidized to form an S-oxide intermediate (M11), which proceeds with a hydrolytic pathway to yield a sulfenic acid (M12) and subsequently the bioreduced active metabolite (M13). To test the long-standing pathway of M2 to M13 via M11, we have chemically synthesized M11 but found it does not undergo the proposed hydrolytic activation in various conditions including in liver microsomal incubations. To seek an alternative mechanism, 18O tracing studies were performed with both H218O and 18O2, and LC-MS studies show that the carboxylate product moiety acquires its O-atom from oxygen instead of water, which rules out M11 as the bioactivation intermediate. To explain the 18O tracing results, a one-step Baeyer-Villiger-like mechanism is proposed for the CYP-dependent thioester cleavage, which features the incorporation of the two O-atoms of O2 into the two product moieties of carboxylate and sulfenic acid. The research presented herein provides a biochemical basis for delineating the clinical pharmacology of a mainstay treatment and expands our understanding of CYP catalysis.


Assuntos
Sistema Enzimático do Citocromo P-450 , Ácidos Sulfênicos , Catálise , Clopidogrel/metabolismo , Clopidogrel/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/metabolismo , Oxirredução , Ácidos Sulfênicos/metabolismo
2.
Turk Kardiyol Dern Ars ; 50(5): 320-326, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35860883

RESUMO

OBJECTIVE: In this study, we aimed to determine whether potent agents affect in-hospital bleeding and mortality compared to clopidogrel in patients with the acute coronary syndrome in whom tirofiban and P2Y12 inhibitor are used together. METHODS: Patients who were treated interventionally between 2015 and 2020 and were using tirofiban were retrospectively screened. Clinical, laboratory, and angiographic findings were obtained from the hospital database. Patients were analyzed by dividing them into clopidogrel and prasugrel/ticagrelor groups. RESULTS: Acute coronary syndrome patients (n = 227) who were treated interventionally were included in this retrospective study. Clopidogrel was given to 93 (41%), ticagrelor to 112 (49.3%), and prasugrel to 22 of the patients (9.7%). Compared to the ticagrelor/prasugrel group, the clopidogrel group was older and more were women, and the history of hypertension and previous coronary artery disease was higher (P, respectively: <.001; .001; .008; .0045). The creatinine value was higher, the basal hemoglobin was lower, and the GRACE (Global Registry of Acute Coronary Events) and CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) scores were higher (P, respectively: .026; .002; .002; <.001). The in-hospital bleeding rate was signifi- cantly higher in the clopidogrel group (P < .001). Although the in-hospital mortality rate was higher, it was not statistically significant (P = .07). Regression analysis showed that GRACE score and gender were associated with in-hospital mortality (P < .001; P=.031, respectively), and only age was associated with in-hospital bleeding (P < .001). No relationship was found with P2Y12 inhibitor. CONCLUSION: In our study, we found that the combined use of potent P2Y12 inhibitor with tiro- fiban in acute coronary syndrome patients treated interventionally was not different from the use of clopidogrel in terms of in-hospital bleeding and mortality.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Clopidogrel/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hospitais , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Estudos Retrospectivos , Ticagrelor/uso terapêutico , Tirofibana/uso terapêutico , Resultado do Tratamento
3.
Cochrane Database Syst Rev ; 7: CD003186, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35900898

RESUMO

BACKGROUND: The main complications of elevated systemic blood pressure (BP), coronary heart disease, ischaemic stroke, and peripheral vascular disease, are related to thrombosis rather than haemorrhage. Therefore, it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated BP. OBJECTIVES: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with elevated BP, including elevations in systolic or diastolic BP alone or together. To assess the effects of antiplatelet agents on total deaths or major thrombotic events or both in these patients versus placebo or other active treatment. To assess the effects of oral anticoagulants on total deaths or major thromboembolic events or both in these patients versus placebo or other active treatment. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to January 2021: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 12), Ovid MEDLINE (from 1946), and Ovid Embase (from 1974). The World Health Organization International Clinical Trials Registry Platform and the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) were searched for ongoing trials.  SELECTION CRITERIA: RCTs in patients with elevated BP were included if they were ≥ 3 months in duration and compared antithrombotic therapy with control or other active treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data for inclusion criteria, our prespecified outcomes, and sources of bias. They assessed the risks and benefits of antiplatelet agents and anticoagulants by calculating odds ratios (OR), accompanied by the 95% confidence intervals (CI). They assessed risks of bias and applied GRADE criteria.  MAIN RESULTS: Six trials (61,015 patients) met the inclusion criteria and were included in this review. Four trials were primary prevention (41,695 patients; HOT, JPAD, JPPP, and TPT), and two secondary prevention (19,320 patients, CAPRIE and Huynh). Four trials (HOT, JPAD, JPPP, and TPT) were placebo-controlled and two studies (CAPRIE and Huynh) included active comparators. Four studies compared acetylsalicylic acid (ASA) versus placebo and found no evidence of a difference for all-cause mortality (OR 0.97, 95% CI 0.87 to 1.08; 3 studies, 35,794 participants; low-certainty evidence). We found no evidence of a difference for cardiovascular mortality (OR 0.98, 95% CI 0.82 to 1.17; 3 studies, 35,794 participants; low-certainty evidence). ASA reduced the risk of all non-fatal cardiovascular events (OR 0.63, 95% CI 0.45 to 0.87; 1 study (missing data in 3 studies), 2540 participants; low-certainty evidence) and the risk of all cardiovascular events (OR 0.86, 95% CI 0.77 to 0.96; 3 studies, 35,794 participants; low-certainty evidence). ASA increased the risk of major bleeding events (OR 1.77, 95% CI 1.34 to 2.32; 2 studies, 21,330 participants; high-certainty evidence). One study (CAPRIE; ASA versus clopidogrel) included patients diagnosed with hypertension (mean age 62.5 years, 72% males, 95% Caucasians, mean follow-up: 1.91 years). It showed no evidence of a difference for all-cause mortality (OR 1.02, 95% CI 0.91 to 1.15; 1 study, 19,143 participants; high-certainty evidence) and for cardiovascular mortality (OR 1.08, 95% CI 0.94 to 1.26; 1 study, 19,143 participants; high-certainty evidence). ASA probably reduced the risk of non-fatal cardiovascular events (OR 1.10, 95% CI 1.00 to 1.22; 1 study, 19,143 participants; high-certainty evidence) and the risk of all cardiovascular events (OR 1.08, 95% CI 1.00 to 1.17; 1 study, 19,143 participants; high-certainty evidence) when compared to clopidogrel. Clopidogrel increased the risk of major bleeding events when compared to ASA (OR 1.35, 95% CI 1.14 to 1.61; 1 study, 19,143 participants; high-certainty evidence). In one study (Huynh; ASA verus warfarin) patients with unstable angina or non-ST-segment elevation myocardial infarction, with prior coronary artery bypass grafting (CABG) were included (mean age 68 years, 79.8% males, mean follow-up: 1.1 year). There was no evidence of a difference for all-cause mortality (OR 0.98, 95% CI 0.06 to 16.12; 1 study, 91 participants; low-certainty evidence). Cardiovascular mortality, non-fatal cardiovascular events, and all cardiovascular events were not available. There was no evidence of a difference for major bleeding events (OR 0.13, 95% CI 0.01 to 2.60; 1 study, 91 participants; low-certainty evidence).  AUTHORS' CONCLUSIONS: There is no evidence that antiplatelet therapy modifies mortality in patients with elevated BP for primary prevention. ASA reduced the risk of cardiovascular events and increased the risk of major bleeding events.  Antiplatelet therapy with ASA probably reduces the risk of non-fatal and all cardiovascular events when compared to clopidogrel. Clopidogrel increases the risk of major bleeding events compared to ASA in patients with elevated BP for secondary prevention.  There is no evidence that warfarin modifies mortality in patients with elevated BP for secondary prevention.  The benefits and harms of the newer drugs glycoprotein IIb/IIIa inhibitors, clopidogrel, prasugrel, ticagrelor, and non-vitamin K antagonist oral anticoagulants for patients with high BP have not been studied in clinical trials. Further RCTs of antithrombotic therapy including newer agents and complete documentation of all benefits and harms are required in patients with elevated BP.


Assuntos
Hipertensão , Tromboembolia , Trombose , Idoso , Anticoagulantes/efeitos adversos , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Tromboembolia/etiologia , Trombose/prevenção & controle , Varfarina/uso terapêutico
4.
BMC Cardiovasc Disord ; 22(1): 301, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780089

RESUMO

BACKGROUND: In the setting of ST-segment elevation myocardial infarction (STEMI), the faster and stronger antiplatelet action of ticagrelor compared to clopidogrel, as well as its pleiotropic effects, could result in a greater degree of cardioprotection and final infarct size (FIS) limitation. The aim of our study was to comparatively evaluate the effect of ticagrelor and clopidogrel on myocardial salvage index (MSI) in STEMI patients undergoing thrombolysis. METHODS: Forty-two STEMI patients treated with thrombolysis were randomized to receive clopidogrel (n = 21) or ticagrelor (n = 21), along with aspirin. Myocardial area at risk (AAR) was calculated according to the BARI and the APPROACH jeopardy scores. FIS was quantified by cardiac magnetic resonance imaging (CMR) performed 5-6 months post-randomization. MSI was calculated as (AAR-FIS)/AAR × 100%. Primary endpoint of our study was MSI. Secondary endpoints were FIS and CMR-derived left ventricular ejection fraction (LVEF) at 5 -6 months post-randomization. RESULTS: By using the BARI score for AAR calculation, mean MSI was 52.25 ± 30.5 for the clopidogrel group and 54.29 ± 31.08 for the ticagrelor group (p = 0.83), while mean MSI using the APPROACH score was calculated at 51.94 ± 30 and 53.09 ± 32.39 (p = 0.9), respectively. Median CMR-derived FIS-as a percentage of LV-was 10.7% ± 8.25 in the clopidogrel group and 12.09% ± 8.72 in the ticagrelor group (p = 0.6). Mean LVEF at 5-6 months post-randomization did not differ significantly between randomization groups. CONCLUSIONS: Our results suggest that the administration of ticagrelor in STEMI patients undergoing thrombolysis offer a similar degree of myocardial salvage, compared to clopidogrel.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Clopidogrel/efeitos adversos , Humanos , Infarto do Miocárdio/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Volume Sistólico , Terapia Trombolítica/efeitos adversos , Ticagrelor/efeitos adversos , Função Ventricular Esquerda
5.
J Physiol Pharmacol ; 73(1)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35793763

RESUMO

To investigate the relationship between plasma microRNA-223 expression and platelet reactivity in patients with acute ischemic stroke (AIS) and to evaluate its predictive value in clopidogrel resistance or high on-treatment platelet reactivity (HTPR). A total of 120 patients with acute ischemic stroke were screened in this study, and 60 patients were included in the acute ischemic stroke group according to the inclusion criteria and platelet reactivity after clopidogrel treatment. control group was 60 non-ischemic stroke patients hospitalized. The levels of phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and adenosine diphosphate-induced platelet aggregation (ADP-PAg) in platelets were detected by flow cytometry. The expression level of plasma microRNA-223 was detected before and after clopidogrel treatment using quantitative real-time polymerase chain reaction (PcR). The AIS group was then divided into the clopidogrel non-HTPR and the clopidogrel HTPR groups based on the relative inhibition rate. We found that: 1) the VASP platelet reactivity index (PRI) was positively correlated with ADP-PAg; 2) before administration, the plasma microRNA-223 expression level and VASP-PRI were higher in the AIS group than in the control group; 3) after administration, the expression level of microRNA-223 was negatively correlated with VASP-PRI; 4) before and after treatment, the plasma microRNA-223 expression level in the clopidogrel HTPR group was lower than in the non-AIS patients; 5) before treatment, there was an interaction between the expression level of microRNA-223 in the plasma and the cYP2c19 loss-of-function (LOF) allele. The study showed that decreased plasma microRNA-223 expression levels in AIS patients indicate an increased risk of clopidogrel HTPR. carrying cYP2c19 LOF alleles may result in the microRNA-223 expression being more distinct. The combined detection of plasma microRNA-223 and cYP2c19 gene polymorphisms may be effective in predicting the occurrence of clopidogrel HTPR in patients with AIS.


Assuntos
AVC Isquêmico , MicroRNAs , Difosfato de Adenosina/farmacologia , Plaquetas/metabolismo , Clopidogrel/farmacologia , Citocromo P-450 CYP2C19/genética , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-35897347

RESUMO

Dual antiplatelet therapy (DAPT) has remained the cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5' diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline for ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.


Assuntos
Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina , Resultado do Tratamento
7.
JAMA Netw Open ; 5(7): e2224157, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35900761

RESUMO

Importance: After the publication of the CHANCE (Clopidogrel in High Risk Patients With Acute Nondisabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke) clinical trials, the American Heart Association/American Stroke Association (AHA/ASA) issued a new class 1, level of evidence A, recommendation for dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) for secondary prevention in patients with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤3). The extent to which variations in DAPT prescribing patterns remain and the extent to which practice patterns in the US are consistent with evidence-based guidelines are unknown. Objective: To evaluate the discharge DAPT prescribing patterns after publication of the new AHA/ASA guidelines and assess the extent of hospital-level variation in the use of DAPT for secondary prevention in patients with minor stroke (NIHSS score ≤3), as indicated by guidelines, and in patients with nonminor stroke (NIHSS score >3), for whom the risks and benefits of DAPT have not been fully established. Design, Setting, and Participants: This multicenter retrospective cohort study involved 132 817 patients from 1890 hospitals participating in the AHA/ASA Get With The Guidelines-Stroke program. Patients who were hospitalized for acute ischemic stroke and prescribed antiplatelet therapy at discharge between October 1, 2019, and June 30, 2020, were included. Exposures: Minor ischemic stroke (NIHSS score ≤3) vs nonminor ischemic stroke (NIHSS score >3). Main Outcomes and Measures: The primary outcome was DAPT prescription at discharge. The extent to which variations in DAPT use were explained at the hospital level was assessed by calculating the median odds ratio (OR), which was derived using multivariable logistic regression analysis and compared the likelihood that 2 patients with identical clinical features admitted to 2 randomly selected hospitals (1 with higher propensity and 1 with lower propensity for DAPT use) would receive DAPT at discharge. Associations between hospital-level DAPT use among patients with minor vs nonminor stroke were evaluated using Pearson ρ correlation coefficients. Results: Among 132 817 patients (median [IQR] age, 68 [59-78] years; 68 768 men [51.8%]), 4282 (3.2%) were Asian, 11 254 (8.5%) were Hispanic, 27 221 (20.5%) were non-Hispanic Black, 84 468 (63.6%) were non-Hispanic White, and 5592 (4.2%) were of other races and/or ethnicities (including American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and unable to determine). Overall, 86 551 patients (65.2%) presented with minor ischemic stroke, and 46 266 patients (34.8%) presented with nonminor ischemic stroke. After the 2019 AHA/ASA guideline updates, 40 661 patients (47.0%) with minor stroke (NIHSS median [IQR] score, 1 [0-2]) and 19 703 patients (42.6%) with nonminor stroke (NIHSS median [IQR] score, 6 [5-9]) received DAPT at discharge. Despite guideline recommendations, 45 890 patients (53.0%) with minor stroke did not receive DAPT. After accounting for patient characteristics, substantial hospital-level variations were found in the use of DAPT in those with minor stroke (median [IQR] hospital-level DAPT prescription rate, 44.8% [33.7%-57.7%]; range, 0%-91.7%; median OR, 2.03 [95% CI, 1.97-2.09]) when comparing 2 patients with identical risk factors discharged from 2 randomly selected hospitals, 1 with higher propensity and 1 with lower propensity for DAPT use. The use of DAPT in patients with nonminor stroke also varied significantly (median [IQR] hospital-level DAPT prescription rate, 41.4% [30.0%-53.8%]; range, 0%-100%; median OR, 1.90 [95% CI, 1.83-1.97]). Overall, hospitals that were more likely to prescribe DAPT for minor strokes were also more likely to prescribe DAPT for nonminor strokes (Pearson ρ = 0.72; P < .001). Conclusions and Relevance: This cohort study found that despite updated AHA/ASA guidelines, more than 50% of patients with minor acute ischemic stroke did not receive DAPT at discharge. In contrast, more than 40% of patients with nonminor stroke received DAPT despite lack of evidence in this setting. These findings suggest that enhancing adherence to evidence-based DAPT practice guidelines may be a target for quality improvement in the treatment of patients with ischemic stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Estudos de Coortes , Humanos , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Prescrições , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle , Estados Unidos
8.
PLoS One ; 17(7): e0272140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35901007

RESUMO

BACKGROUND: Triple antithrombotic therapy, including dual antiplatelet therapy and oral anticoagulant (OAC), is recommended for a short-term period after percutaneous coronary intervention (PCI) in patients requiring anticoagulation therapy. The purpose of this study was to compare in-hospital clinical outcomes between low-dose prasugrel (3.75 mg/day) and clopidogrel, as part of triple antithrombotic therapy, using a large database in Japan. METHODS: Patients with ischemic heart disease who underwent PCI between January 2015 and December 2019, and were prescribed triple therapy with aspirin, a P2Y12 inhibitor (clopidogrel or low-dose prasugrel), and OAC (direct oral anticoagulant: DOAC or vitamin K antagonist: VKA), were selected from the Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes were myocardial infarction, ischemic stroke, bleeding stroke, gastrointestinal bleeding, and blood transfusion. RESULTS: Overall, 5,777 patients were eligible in this analysis. The patients were divided into 4 subgroups according to the type of P2Y12 inhibitor and OAC: clopidogrel/DOAC (n = 1,628), clopidogrel/VKA (n = 1,334), prasugrel/DOAC (n = 1,607), and prasugrel/VKA (n = 1,208). There was no significant difference in the incidence of death and gastrointestinal bleeding among the 4 subgroups. The prasugrel/DOAC group had significantly lower incidence of MI (OR 0.566, 95% CI 0.348-0.921). The incidence of ischemic stroke was significantly lower in the prasugrel/DOAC group (OR 0.701, 95% CI 0.502-0.979), and significantly higher in the clopidogrel/VKA group (OR 1.680, 95% CI 1.273-2.216). Need for blood transfusion was less frequent in the prasugrel/DOAC group (OR 0.729, 95% CI 0.598-0.890), and more frequent in both the clopidogrel/VKA group (OR 1.424, 95% CI 1.187-1.708) and the prasugrel/VKA group (OR 1.633, 95% CI 1.367-1.950). CONCLUSIONS: Combination of low-dose prasugrel and DOAC was associated with lower incidence of MI, ischemic stroke, and blood transfusion. Low-dose prasugrel may be feasible as part of triple therapy in patients undergoing PCI.


Assuntos
AVC Isquêmico , Intervenção Coronária Percutânea , Anticoagulantes/efeitos adversos , Clopidogrel , Quimioterapia Combinada , Fibrinolíticos/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Resultado do Tratamento
10.
Medicine (Baltimore) ; 101(27): e29824, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801776

RESUMO

BACKGROUND: The 2020 European Society of Cardiology guidelines do not recommend pretreatment for nonST-segment elevation myocardial infarction (NSTEMI) patients with unclear coronary anatomy, which is inconsistent with our routine preoperative approach to loading P2Y12 receptor inhibitors (e.g., preoperative loading of 300 mg of clopidogrel). OBJECTIVES: The purpose of our study was to compare the safety and effectiveness of P2Y12 inhibitors administered before coronary angiography or at least before percutaneous coronary intervention (PCI) with during or after PCI. METHODS: Cochrane, PubMed, and Embase databases were searched. The primary effect endpoint and safety endpoint were any-cause death and major bleeding, respectively. Major adverse cardiovascular events, myocardial infarction and revascularization were also analyzed. RESULTS: Our search identified 9 trials. P2Y12 inhibitor pretreatment was associated with lower death from any cause (OR 0.62, 95% CI 0.53-0.72, P < 0.00001) without increasing the risk of bleeding (OR 1.02, 95% CI 0.80-1.30, P = 0.89). However, prasugrel or ticagrelor pretreatment was not associated with a lower risk of mortality (OR 0.70, 95% CI 0.31-1.59, P = 0.40) and increased the risk of bleeding (OR 1.67, 95% CI 1.10-2.54, P = 0.02). CONCLUSIONS: In summary, clopidogrel pretreatment was associated with significantly lower mortality, major adverse cardiovascular events, myocardial infarction and revascularization with no increase in major bleeding. However, these advantages were not observed with prasugrel or ticagrelor pretreatment.


Assuntos
Síndrome Coronariana Aguda , Antagonistas do Receptor Purinérgico P2Y , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
11.
J Infect Dev Ctries ; 16(6): 981-992, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35797292

RESUMO

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.


Assuntos
COVID-19 , Transtornos Cerebrovasculares , Aspirina , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Clopidogrel , Enoxaparina/análogos & derivados , Humanos , Manitol , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Piracetam , Pirazóis , Piridonas , Estudos Retrospectivos , SARS-CoV-2
13.
Med Sci Monit ; 28: e936953, 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35869616

RESUMO

BACKGROUND This study aimed to investigate the optimum time to reintroduce the original antiplatelet drugs after upper gastrointestinal hemorrhage in patients as secondary prevention for cardiovascular and cerebrovascular diseases. MATERIAL AND METHODS After the upper gastrointestinal bleeding stopped, patients were randomly divided according to the oral antiplatelet drugs administered. The aspirin group was further divided into 3-day and 7-day aspirin groups. The patients who took aspirin and clopidogrel were randomly divided into 3 groups: 0-day aspirin+3-day clopidogrel; 0-day aspirin+7-day clopidogrel; and 3-day aspirin+7-day clopidogrel. The recovery time, rebleeding rate, incidence of cardiovascular and cerebrovascular events, and death were observed. RESULTS The 3-day aspirin group had more rebleeding, reduced risk of cardiovascular and cerebrovascular events, and a similar mortality rate compared to the other groups. In the aspirin+clopidogrel group, the 0-day aspirin+3-day clopidogrel group had the highest rebleeding rate and the lowest risk of cardiovascular and cerebrovascular events. The 3-day aspirin+7-day clopidogrel group had the highest risk of cardiovascular and cerebrovascular events and increased hospitalization time. The risk of rebleeding and cardiovascular and cerebrovascular events was lower in the 0-day aspirin+7-day clopidogrel group, and the overall mortality rate was the lowest in this group. CONCLUSIONS In patients receiving only aspirin, this drug should be reintroduced as soon as possible after peptic ulcer hemorrhage. Aspirin and clopidogrel are dual antiplatelet drugs used for the secondary prevention of cardiovascular diseases. In patients under dual-drug therapy, aspirin should not be stopped, while clopidogrel should be restarted in about 7 days.


Assuntos
Inibidores da Agregação Plaquetária , Ticlopidina , Aspirina/efeitos adversos , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Ticlopidina/uso terapêutico
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(6): 809-813, 2022 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35837782

RESUMO

In this study, we reported a young male patient with acute chest pain who was diagnosed as myocardial infarction. The regular medication was performed following coronary intervention. Under such condition, this patient had 3 times myocardial infarction within a half month. The laboratory results showed that there might be a state of hypercoagulability. Aspirin combined with clopidogrel and other treatment were administrated. Meanwhile, the examination demonstrated that there was aspirin-resistant in the patient. The antiplatelet drug and extended anticoagulation therapy were carried out. There was no further myocardial infarction, and no coronary arteries stenosis was found in the re-examination angiography. Aspirin resistance and hypercoagulability should be considered when patients occurred the repeated myocardial infarction after regular medication and coronary intervention. Replacement of the antiplatelet treatment or combination with anticoagulant therapy is necessary in similar patient to avoid the sever consequence.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombofilia , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Trombofilia/tratamento farmacológico , Resultado do Tratamento
16.
J Am Heart Assoc ; 11(11): e024992, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35656996

RESUMO

Background The objective of the study was to assess the cost-effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke. Methods and Results A Markov model decision tree was used to examine lifetime costs and quality-adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100 mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10 000 cohorts of 10 000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10 000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13 488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness-to-pay threshold of $50 000/QALY, average net monetary benefit from the addition of cilostazol was $42 743 per patient over their lifetime. Conclusions Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.


Assuntos
Aspirina , Acidente Vascular Cerebral , Cilostazol/uso terapêutico , Clopidogrel/uso terapêutico , Análise Custo-Benefício , Humanos , Cadeias de Markov , Inibidores da Agregação Plaquetária/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Prevenção Secundária , Ticlopidina/efeitos adversos
17.
J Am Heart Assoc ; 11(12): e024709, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35699175

RESUMO

Background TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype-guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss-of-function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex-specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional-hazards models. Among 5276 randomized patients, loss-of-function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P=0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P=0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value (Pint=0.59) or BARC bleeding (Pint=0.47) nor for sex and genotype (MACE Pint=0.15, and BARC bleeding Pint=0.60). Conclusions CYP2C19 loss-of-function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype-guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Intervenção Coronária Percutânea , Fatores Sexuais , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento
19.
Anatol J Cardiol ; 26(6): 434-441, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35703479

RESUMO

BACKGROUND: Although current guidelines recommend ticagrelor to clopidogrel for patients with acute coronary syndrome, its benefit and risk are unclear for East Asians. This meta-analysis was performed to assess the efficacy and safety of ticagrelor in East Asian patients with acute coronary syndrome. METHODS: Medline, EMBASE, and Cochrane Databases were searched from inception to July, 2021, for randomized controlled trials comparing ticagrelor with clopidogrel in East Asian patients with acute coronary syndrome. Major adverse cardiovascular events and bleeding events were assessed by using Mantel-Haenszel-pooled risk ratio and 95% con- fidence interval. RESULTS: Five randomized controlled trials identified 2752 patients with acute coronary syndrome. Compared with clopidogrel, ticagrelor had no statistical difference of major adverse cardiovascular events (RR 0.87; 95% CI 0.52-1.45; P = .58), all cause death (RR 0.90, 95% CI 0.62-1.32; P = .60), cardiovascular death (RR 0.90, 95% CI 0.47-1.72; P = .74), myo- cardial infarction (RR 0.91, 95% CI 0.52-1.58; P = .73), and stroke (RR 0.87, 95% CI 0.48-1.57; P = .64). Despite ticagrelor did not increase the incidence of fatal bleeding (RR 2.49, 95% CI 0.79-7.87; P = 0.12), the risks of all bleeding (RR 1.71, 95% CI 1.36-2.16; P < .00001), major bleeding (RR 1.51, 95% CI 1.12-2.04; P = .007), non-coronary artery bypass grafting major bleeding (RR 1.83, 95% CI 1.23-2.71; P = .003), and minor bleeding (RR 1.92, 95% CI 1.40-2.64; P < .0001) were significantly higher. CONCLUSIONS: Although there was no significant difference in the incidence of fatal bleed- ing, ticagrelor displayed similar efficacy and dramatically increased the risk of otherbleeding events.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor/uso terapêutico , Resultado do Tratamento
20.
Acta Med Acad ; 51(1): 29-34, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35695400

RESUMO

OBJECTIVE: Clopidogrel is a common antiplatelet used as secondary prevention of ischemic stroke, known to have better efficacy than aspirin, with a equivalent safety profile. However, clopidogrel resistance is not uncommon but has not been widely studied in Asia. This study will further assess clopidogrel resistance and its risk factors. MATERIALS AND METHODS: A cross-sectional study was conducted at Rumah Sakit Universitas, Indonesia, and Rumah Sakit Cipto Mangunkusumo, Indonesia in 2020-2021. All patients had had at least one episode of ischemic stroke. Clopidogrel resistance was assessed using a VerifyNow assay. RESULTS: 57 subjects were enrolled in this study. We found 15.8% of subjects were clopidogrel resistant. Gender was significantly associated with clopidogrel resistance, with males having 80% lower clopidogrel resistance (OR 0.2 (95% CI 0.022 - 0.638); P=0.006). Meanwhile, smoking was not associated with clopidogrel responsiveness (P=0.051). We found no association between haemoglobin, blood glucose, HbA1c, cholesterol, liver enzymes, serum urea concentration or creatinine levels and clopidogrel resistance. CONCLUSION: Clopidogrel remains an effective treatment to prevent recurrent ischemic stroke in Indonesia. Further studies are needed to assess gene polymorphism and clopidogrel resistance, which may explain the findings of this study.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Clopidogrel/uso terapêutico , Estudos Transversais , Quimioterapia Combinada , Humanos , Indonésia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Ticlopidina/efeitos adversos , Resultado do Tratamento
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