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1.
Lancet ; 395(10233): 1374-1381, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334703

RESUMO

BACKGROUND: Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37). FINDINGS: Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). INTERPRETATION: In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. FUNDING: ZonMw.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Feminino , Humanos , Masculino , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
2.
Life Sci ; 247: 117429, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061670

RESUMO

AIMS: Hypercholesterolemia is a hazard for increasing susceptibility of the heart to myocardial infarction (MI) by inducing platelet hyperaggregability. Clopidogrel and prasugrel have documented cardioprotective effects in clinical studies. Herein, we investigated whether clopidogrel and prasugrel could protect against isoproterenol-induced acute MI (A-MI) under hypercholesterolemic conditions in rats. MAIN METHODS: Dietary hypercholesterolemic rats were subjected to acute doses of isoproterenol. Serum lipids, inflammatory markers, aortic endothelin1 and endothelial nitric oxide synthase (eNOS) mRNAs expression and immunexpression of BCL2 were determined. KEY FINDINGS: Hypercholesterolemic rats showed infiltration of inflammatory cells and reduction in aortic wall thickness, deposition of fibrous tissue between cardiac muscle fibers. Protective doses of prasugrel or clopidogrel for 28 days before A-MI increased survival, amended the ECG parameters -including ST segment elevation- and improved the histopathological picture in hypercholesterolemic rats. This was coupled with reductions in platelet aggregation, creatine kinase-MB activity, endothelin 1, systemic inflammation and cardiac lipid peroxidation and increment in aortic eNOS expression. Clopidogrel and prasugrel groups showed enhanced BCL2 expression in cardiac fibers and aortic wall. SIGNIFICANCE: Prasugrel and clopidogrel protected against A-MI via anti-aggregatory and anti-inflammatory effects. These results add to the value of these drugs in correcting cardiovascular dysfunction in patients vulnerable to A-MI after confirmation by appropriate human studies.


Assuntos
Clopidogrel/uso terapêutico , Hipercolesterolemia/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Animais , Sistema Cardiovascular/efeitos dos fármacos , Creatina Quinase Forma MB/metabolismo , Endotelina-1/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Modelos Animais , Mortalidade , Óxido Nítrico Sintase Tipo III/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Resultado do Tratamento
3.
Am Heart J ; 220: 108-115, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31809991

RESUMO

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.


Assuntos
Síndrome Coronariana Aguda/terapia , Hemorragia/epidemiologia , Isquemia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Clopidogrel/uso terapêutico , Feminino , Hemorragia/etiologia , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Complicações Pós-Operatórias/etiologia , Cloridrato de Prasugrel/uso terapêutico , Recidiva , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Fatores de Tempo
4.
Cell Physiol Biochem ; 53(6): 961-981, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31820856

RESUMO

BACKGROUND/AIMS: We assessed the effects of ticagrelor, aspirin and prasugrel, started 7days after myocardial ischemia-reperfusion injury on remodeling, inflammation and fibrosis in the rat. We examined whether ticagrelor can affect the number of progenitor cells in the border zone. Ticagrelor, started 24h after myocardial ischemia-reperfusion injury, attenuates the decrease in heart function and adverse remodeling, an effect which is blocked by aspirin. METHODS: Rats underwent 40min ischemia followed by reperfusion. Oral dosing with vehicle, ticagrelor (300mg/kg/d), aspirin (20mg/kg/d), their combination or prasugrel (15mg/kg/d) started 7days after infarction. Echocardiography was used to assess systolic function. Heart tissue were analyzed by rt-PCR, immunoblotting, ELISA and immunohistochemistry 2weeks after infarction. RESULTS: Both ticagrelor and aspirin attenuated the decrease in systolic function and remodeling, an effect that was blocked by their combination. Ticagrelor and aspirin attenuated the increase in ANP, BNP, collagen-I and collagen-III. Again, the effect was blocked by their combination. Ticagrelor increased c-Kit, Sca-1, Ki-67, CD34, attenuated the decrease in CD105 mRNA levels, and attenuated the increase in CD31, whereas aspirin increased Ki-67, suppressed the increase in CD31 and attenuated the decrease in CD105 mRNA levels. Prasugrel did not display any effects. CONCLUSION: Ticagrelor attenuated adverse remodeling and deterioration of left ventricular systolic function despite starting treatment after the myocardial ischemia-reperfusion injury is completed. Aspirin had similar effects; however, when combined with ticagrelor, the protective effects were significantly attenuated. Ticagrelor increased the levels of several markers of stem cells and regeneration, suggesting cardiac healing by recruiting regenerative cells into the infarct.


Assuntos
Apoptose/efeitos dos fármacos , Infarto do Miocárdio/patologia , Inibidores da Agregação de Plaquetas/farmacologia , Ticagrelor/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Aspirina/farmacologia , Aspirina/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Endoglina/genética , Endoglina/metabolismo , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/farmacologia , Cloridrato de Prasugrel/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Ticagrelor/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos
5.
Am J Cardiol ; 124(12): 1807-1812, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31668345

RESUMO

The use of prasugrel and ticagrelor as part of dual antiplatelet therapy is increasing in patients after percutaneous coronary intervention (PCI). Accordingly, we aimed to evaluate their prescription patterns in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry. We analyzed patients enrolled in NCDR PINNACLE registry from January 2013 to March 2015 who underwent PCI with drug-eluting stent and were prescribed dual antiplatelet therapy. All patients received aspirin. The primary study outcome was a 3-level variable denoting the second antiplatelet agent prescribed: (1) clopidogrel, (2) prasugrel, or (3) ticagrelor. Baseline characteristics were compared among the 3 groups. Odds ratios and 95% credible intervals were calculated from a nested hierarchical Bayesian logistic regression models to identify independent predictors of prescription of antiplatelet medications, incorporating practice and provider as random effects. Our study cohort consisted of 26,710 patients during our study period January 2013 to March 2015. Seventy nine percent of patients were prescribed clopidogrel, 12% prasugrel, and 11% ticagrelor. Patients aged ≥75 years, women, history of tobacco use, Peripheral Arterial Disease (PAD), hypertension, diabetes, previous vascular complication, heart failure, and stroke/transient ischemic attack were more likely to be on clopidogrel than prasugrel or ticagrelor. The relative percentages of ticagrelor and prasugrel were higher in patients with history of myocardial infarction, compared with those without myocardial infarction. In summary, our study highlights the prescription patterns associated with prescription of antiplatelet agents after PCI. We found that both ticagrelor and prasugrel were mostly prescribed per the current practice guidelines, thus reflecting appropriate guideline adherence by practices in NCDR PINNACLE registry.


Assuntos
Clopidogrel/uso terapêutico , Estenose Coronária/terapia , Uso de Medicamentos/estatística & dados numéricos , Intervenção Coronária Percutânea/métodos , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Teorema de Bayes , Estudos de Coortes , Terapia Combinada , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Stents Farmacológicos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Prescrições/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
6.
Expert Rev Cardiovasc Ther ; 17(10): 717-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31583920

RESUMO

Introduction: Inhibition of P2Y12 platelet receptors consists a crucial target of pharmacologic treatment in acute coronary syndrome patients. Several controversial issues however still remain and these are analyzed.Areas covered: The significance of early and strong platelet inhibition in the early phase of STEMI and the role of pretreatment are discussed. Concerns regarding morphine administration are raised. The role of crushing integral tablets to expedite the onset of action of oral P2Y12 inhibitors is emphasized. New data on the intravenous cangrelor are reported. Antiplatelet therapies as adjunct to thrombolysis, as well as the role of de-escalation antiplatelet therapy are analyzed.Expert opinion: Pharmacodynamic studies convincingly demonstrate a gap in the onset of antiplatelet action in STEMI cases, even when prasugrel or ticagrelor loading dose is used. The clinical benefit, however, of the early platelet inhibition and pretreatment is not entirely clear. Morphine delays the onset of action of oral agents, while this is expedited by crushing the integral tablets. Cangrelor devoids of these deficiencies by achieving fast and strong platelet inhibition in all clinical scenarios. Concomitant administration of novel antiplatelet agents with thrombolysis and de-escalation of antiplatelet treatment necessitate further study to reach definite conclusion.


Assuntos
Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Administração Intravenosa , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/administração & dosagem
7.
Mo Med ; 116(4): 303-307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527979

RESUMO

Aspirin is recommended for patients with acute ischemic stroke within 24 hours of symptom onset. It may be beneficial for dual antiplatelet therapy including clopidogrel and aspirin to be administered in patients with minor stroke or transient ischemic attack for early secondary prevention, however, bleeding risk remains uncertain. This article will review the published literature concerning the role of dual antiplatelet therapy for secondary stroke prevention with focus on balancing both risk and benefit.


Assuntos
Terapia Antiplaquetária Dupla , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Terapia Antiplaquetária Dupla/métodos , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/administração & dosagem , Ticagrelor/uso terapêutico
8.
Value Health ; 22(9): 988-994, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31511188

RESUMO

BACKGROUND: The threshold of sufficient evidence for adoption of clinically- and genomically-guided precision medicine (PM) has been unclear. OBJECTIVE: To evaluate evidence thresholds for clinically guided PM versus genomically guided PM. METHODS: We develop an "evidence threshold criterion" (ETC), which is the time-weighted difference between expected value of perfect information and incremental net health benefit minus the cost of research, and use it as a measure of evidence threshold that is proportional to the upper bound of disutility to a risk-averse decision maker for adopting a new intervention under decision uncertainty. A larger (more negative) ETC value indicates that only decision makers with low risk aversion would adopt new intervention. We evaluated the ETC plus cost of research (ETCc), assuming the same cost of research for both interventions, over time for a pharmacogenomic (PGx) testing intervention and avoidance of a drug-drug interaction (aDDI) intervention for acute coronary syndrome patients indicated for antiplatelet therapy. We then examined how the ETC may explain incongruous decision making across different national decision-making bodies. RESULTS: The ETCc for PGx increased over time, whereas the ETCc for aDDI decreased to a negative value over time, indicating that decision makers with even low risk aversion will have doubts in adopting PGx, whereas decision makers who are highly risk-averse will continue to have doubts about adopting aDDI. National recommendation bodies appear to be consistent over time within their own decision making, but had different levels of risk aversion. CONCLUSION: The ETC may be a useful metric for assessing policy makers' risk preferences and, in particular, understanding differences in policy recommendations for genomic versus clinical PM.


Assuntos
Testes Farmacogenômicos/economia , Medicina de Precisão/economia , Avaliação da Tecnologia Biomédica/métodos , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/economia , Clopidogrel/uso terapêutico , Análise Custo-Benefício , Citocromo P-450 CYP2C19/genética , Tomada de Decisões , Interações Medicamentosas , Humanos , Modelos Econômicos , Testes Farmacogenômicos/métodos , Inibidores da Agregação de Plaquetas/economia , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/economia , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão/métodos , Inibidores da Bomba de Prótons/farmacologia , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Ticagrelor/economia , Ticagrelor/uso terapêutico , Incerteza
9.
Can J Cardiol ; 35(10): 1377-1385, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31492492

RESUMO

BACKGROUND: Robust comparisons between oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous coronary intervention are lacking. We sought to evaluate outcomes on the basis of P2Y12 inhibitor therapy in patients from the Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI (TOTAL) trial. METHODS: We grouped 9932 patients according to P2Y12 inhibitor at hospital discharge: clopidogrel (n = 6500; 65.5%), prasugrel (n = 1244; 12.5%), or ticagrelor (n = 2188; 22.0%). The primary composite end point of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure was examined at 1 year. Secondary efficacy and safety end points were also assessed. Cox proportional hazard ratios were determined and adjusted for confounders via propensity scoring. RESULTS: Baseline characteristics differing between the 3 groups were mainly age 75 years or older, diabetes, and previous stroke. After adjustment, ticagrelor use was associated with a lower rate of the primary composite outcome compared with clopidogrel (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.91; P < 0.02) and prasugrel (aHR, 0.65; 95% CI, 0.48-0.89; P = 0.02). Prasugrel use was not associated with a lower rate of the primary outcome compared with clopidogrel (aHR, 1.09; 95% CI, 0.86-1.39; P > 0.99). Neither prasugrel nor ticagrelor were associated with increased risk of stroke compared with clopidogrel. Compared with clopidogrel, ticagrelor was associated with significantly lower rates of major bleeding. CONCLUSIONS: In this observational analysis of STEMI patients who underwent primary percutaneous coronary intervention, ticagrelor was associated with improved outcomes compared with clopidogrel and prasugrel. An appropriately powered randomized trial is needed to confirm these findings.


Assuntos
Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Ticagrelor/uso terapêutico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
10.
N Engl J Med ; 381(17): 1621-1631, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31479209

RESUMO

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).


Assuntos
Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Método Simples-Cego , Stents , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
11.
N Engl J Med ; 381(16): 1524-1534, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31475799

RESUMO

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Trombose Coronária/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
12.
Pharmacotherapy ; 39(9): 912-920, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332815

RESUMO

STUDY OBJECTIVE: To compare the effectiveness and safety of ticagrelor versus prasugrel in preventing recurrent cardiovascular disease (CVD) and major bleeding events in patients with acute coronary syndrome (ACS). DESIGN: Retrospective cohort analysis. DATA SOURCE: Truven Commercial and Medicare Supplemental claims database (2011-2016). PATIENTS: Study consisted of adults with ACS who newly initiated ticagrelor or prasugrel within 7 days of their first ACS diagnosis and had no prior use for at least 12 months; after propensity score matching, 10,073 patients were in each group. METHODS: The primary study outcomes, first occurrence of a recurrent nonfatal CVD event (composite of myocardial infarction and stroke) and occurrence of a major bleeding event, were compared between the ticagrelor and prasugrel groups. Secondary outcomes included occurrence of minor bleeding events, defined based on the presence of bleeding events in outpatient claims. Cox proportional hazards models after propensity score matching were used to obtain the hazard ratio (HR) and 95% confidence interval (CI). In the Cox proportional hazards model, the use of ticagrelor was associated with a decreased risk of recurrent nonfatal CVD events (HR 0.80, 95% CI 0.70-0.92) and major bleeding events (HR 0.54, 95% CI 0.41-0.70) compared with prasugrel. Additionally, the use of ticagrelor was associated with a lower risk of minor bleeding events compared with prasugrel (HR 0.71, 95% CI 0.65-0.78). CONCLUSION: In this population-based cohort of incident ACS patients, ticagrelor was associated with a reduced rate of recurrent nonfatal CVD events, major and minor bleeding events compared with prasugrel.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Prevenção Secundária/métodos , Ticagrelor/uso terapêutico , Fatores Etários , Idoso , Comorbidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Revisão da Utilização de Seguros , Masculino , Medicare , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/efeitos adversos , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores Sexuais , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Estados Unidos
13.
Cardiology ; 142(4): 203-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266007

RESUMO

BACKGROUND: Incidence and reasons of dual antiplatelet therapy (DAPT) discontinuation and switching between P2Y12 inhibitors in acute coronary syndrome (ACS) patients treated with a stent have been poorly studied. METHODS AND RESULTS: In a prospective single-center study, 283 consecutive patients presenting with ACS were treated with stent implantation between July 2015 and January 2016. Follow-up was achieved at 12 months in 273 patients using the electronic patient file and telephone interview. Switching from clopidogrel to a new antiplatelet agent (ticagrelor or prasugrel) or vice versa occurred in 60 (21.2%) patients. The most frequent reasons for switching were medical decisions not associated with bleeding events and concomitant use of chronic oral anticoagulation. Among the patients with a 1-year follow-up, 42 (15.4%) prematurely discontinued DAPT; 25 of them did so due to the need for an invasive procedure. DAPT premature discontinuation was not significantly associated with an increased 1-year risk of cardiovascular death or serious cardiac ischemic events (HR 2.08 [CI 95%: 0.88-4.94, p = 0.099]). CONCLUSIONS: DAPT discontinuation and switching between P2Y12 inhibitors are not uncommon in patients with ACS treated with a stent. The most frequent reasons were the need for an invasive procedure and medical decisions.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/cirurgia , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/uso terapêutico , Tomada de Decisões , Quimioterapia Combinada , Stents Farmacológicos , Terapia Antiplaquetária Dupla , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos
14.
JAMA ; 321(24): 2414-2427, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237644

RESUMO

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Idoso , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico
15.
Am J Cardiol ; 124(3): 373-380, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31146891

RESUMO

The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in >75% and <25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p < 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 [95% confidence interval 0.83 to 0.93], p < 0.001), multivariable analysis (hazard ratio = 0.82 [0.77 to 0.88], p < 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.


Assuntos
Uso de Medicamentos/estatística & dados numéricos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Abciximab/uso terapêutico , Clopidogrel/uso terapêutico , Terapia Combinada , Uso de Medicamentos/tendências , Eptifibatida/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Reino Unido
16.
Eur J Clin Invest ; 49(8): e13149, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172515

RESUMO

BACKGROUND: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. DESIGN: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12-inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. RESULTS: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. CONCLUSION: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , MicroRNAs/sangue , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/uso terapêutico , Plaquetas/metabolismo , Clopidogrel/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico
17.
Eur J Clin Pharmacol ; 75(9): 1201-1210, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197411

RESUMO

PURPOSE: The POPular Risk Score was developed for the selective intensification of P2Y12 inhibitor treatment with prasugrel instead of clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI) with stent implantation. This score is based on platelet reactivity (VerifyNow P2Y12 assay), CYP2C19 genotyping, and clinical risk factors. Our aim was to determine if the use of this score in clinical practice is associated with a reduction in thrombotic events without increasing bleeding events. METHODS: In a single-center prospective cohort study, patients with a high risk score were treated with prasugrel and patients with a low risk score with clopidogrel. The risk score-guided cohort was compared with a historic cohort of clopidogrel-treated patients. The endpoint consisted of all-cause death, myocardial infarction, stroke, or stent thrombosis during 1 year of follow-up. TIMI major and minor bleeding events were also analyzed. RESULTS: The guided cohort contained 1127 patients, 26.9% of whom were switched to prasugrel according to the POPular Risk Score. The historic cohort contained 893 patients. The incidence of the combined thrombotic endpoint was significantly lower in the guided cohort as compared with the historic cohort (8.4% versus 3.7%, p < 0.001). This strategy was safe with respect to bleeding (4.0% versus 1.3%, p < 0.001, for TIMI major or minor bleeding). Results were comparable after multivariate and propensity score matched and weighted analysis. CONCLUSION: Selective intensification of P2Y12 inhibitor treatment after non-urgent PCI based on the POPular Risk Score is associated with a reduction in thrombotic events without an increase in bleeding events.


Assuntos
Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Clopidogrel/efeitos adversos , Citocromo P-450 CYP2C19/metabolismo , Feminino , Genótipo , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Testes de Função Plaquetária , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Risco , Acidente Vascular Cerebral/prevenção & controle , Trombose/prevenção & controle
18.
Thromb Haemost ; 119(9): 1527-1538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226717

RESUMO

OBJECTIVES: This prespecified analysis of the TROPICAL-ACS trial aimed to assess the impact of gender on clinical outcomes and platelet reactivity (PR) following guided de-escalation of dual antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients. BACKGROUND: Guided de-escalation of DAPT was recently identified as an effective alternative treatment strategy in ACS. METHODS: We used Cox proportional hazards models and linear regression analysis to assess the interaction of gender with clinical endpoints and PR. RESULTS: In both male (n = 2,052) and female (n = 558) patients, the 1-year incidence of the primary endpoint did not differ in guided de-escalation versus control group patients (male: 7.0% vs. 9.0%; hazard ratio [HR], 0.78, 95% confidence interval [CI], 0.57-1.06, p = 0.11; female: 8.4% vs. 9.2%; HR, 0.92, 95% CI, 0.53-1.62, p = 0.76, p int = 0.60). The 1-year incidence of combined ischemic events (male: 2.5% vs. 3.3%; HR, 0.76, 95% CI, 0.46-1.26, p = 0.29; female: 2.2% vs. 2.8%; HR, 0.78,95% CI, 0.27-2.25, p = 0.65, p int = 0.96) as well as Bleeding Academic Research Consortium ≥ 2 bleeding (male: 4.6% vs. 6.0%; HR, 0.77, 95% CI, 0.52-1.12, p = 0.17; female: 6.2% vs. 6.4%; HR, 0.99, 95% CI, 0.51-1.92, p = 0.97, p int = 0.51) was similar in the guided de-escalation versus control group for both male and female patients. Interaction testing revealed no significant impact of gender on PR levels (prasugrel or clopidogrel) across treatment groups (p int = 0.72). CONCLUSION: Guided de-escalation of DAPT appears to be equally safe and effective in women and men. Especially in patients with increased bleeding risk and independent from gender, a guided DAPT de-escalation strategy may be used as an alternative treatment strategy. CLINICAL TRIAL REGISTRATION: URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.


Assuntos
Síndrome Coronariana Aguda/terapia , Plaquetas/fisiologia , Clopidogrel/uso terapêutico , Terapia Antiplaquetária Dupla , Cloridrato de Prasugrel/uso terapêutico , Fatores Sexuais , Idoso , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Ativação Plaquetária , Resultado do Tratamento
19.
Clin Adv Hematol Oncol ; 17(4): 234-243, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31188815

RESUMO

BACKGROUND: Sickle cell disease (SCD) is the most common hemoglobinopathy, occurring worldwide, and vaso-occlusive events (VOEs) are its paramount, hallmark clinical manifestation. Evidence exists that platelets play an important role in generating VOEs. OBJECTIVE: To assess the clinical benefits and harms of antiplatelet agents for preventing VOEs in patients with SCD. METHODS: We conducted searches of the Cochrane Central Register of Controlled Trials (CENTRAL; up to 2018, issue 3 of 12), PubMed/MEDLINE (up to April 20, 2018), and the Excerpta Medica database (EMBASE; from 1980 to week 16 of 2018). We also searched the Latin American and Caribbean Health Sciences Literature (LILACS) database, the US Food and Drug Administration (FDA) website, the European Medicines Agency (EMA) website, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and www.ClinicalTrials.gov. We checked the bibliographies of included studies and any relevant systematic reviews. Our systematic review included randomized clinical trials (RCTs) conducted in people who had SCD without VOEs at trial entry. Eligible trials compared a single or combination treatment regimen (with each treatment classified as a conventional or nonconventional antiplatelet agent) with conventional care, placebo, or another regimen. No restrictions were placed on the route of administration, dose, frequency, or duration of treatment. We selected RCTs, assessed the risk for bias, and extracted data in a duplicate and independent fashion. We estimated risk ratios for dichotomous outcomes and mean differences for continuous outcomes. We also subjected our analyses to a random-effects model, and Trial Sequential Analysis (TSA) was used. We used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to assess the overall quality of data for each individual outcome. RESULTS: We identified 5 RCTs (N=747) that met our criteria. Of these, 4 trials were multicenter and multinational. The trials included patients of all ages and assessed prasugrel, ticagrelor, crizanlizumab, and aspirin vs either placebo or no intervention. The most frequent route of administration was oral. The trials were small and carried a high risk for bias, given that pharmaceutical companies sponsored 4 of them. None of the trials reported information on quality of life. No meta-analysis was performed owing to heterogeneity in the ages of the participants and in the interventions. No single trial showed evidence of certainty regarding all-cause mortality. One trial showed uncertainty in comparing prasugrel vs placebo for preventing VOEs in patients younger than 18 years (relative risk [RR], 0.92; 95% CI, 0.80 to 1.06; low quality of evidence). TSA for this outcome suggested that a new trial should be conducted. One trial found a difference in the size effect of uncomplicated VOEs, favoring high-dose crizanlizumab vs placebo (mean difference, -1.50; 95% CI, -2.61 to -0.39; very low quality of evidence). No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo. The overall incidence of harms in any intervention did not differ from that in the control. CONCLUSIONS: The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD. This conclusion was based on small RCTs that carried a high risk for bias. No conclusive evidence exists regarding relevant clinical outcomes because the evidence is limited and of very low quality.


Assuntos
Anemia Falciforme/complicações , Inibidores da Agregação de Plaquetas/uso terapêutico , Doenças Vasculares/prevenção & controle , Adulto , Anemia Falciforme/fisiopatologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Mortalidade , Estudos Multicêntricos como Assunto , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/classificação , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Resultado do Tratamento , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia
20.
Intern Med ; 58(16): 2315-2322, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31118376

RESUMO

Objective Although several clinical trials have shown that the mid- and long-term safety and efficacy of prasugrel are better than those of clopidogrel after percutaneous coronary intervention (PCI), there are few data regarding the short-term safety. Methods In this study, we retrospectively analyzed the short-term (72 hours) PCI-related bleeding complications and mid-term (12 months) efficacy in 250 consecutive coronary artery disease patients who underwent PCI and received aspirin plus prasugrel (prasugrel group; 67.7±10.0 years, 200 men). Patients The comparison group consisted of 250 age- and gender-matched patients who received aspirin plus clopidogrel (clopidogrel group: 67.2±11.2 years, 199 men). Results The incidence of a composite of PCI-related bleeding complications in the acute phase post-PCI was significantly higher in the prasugrel group than in the clopidogrel group (22.4% vs. 13.2%, p=0.007), although the incidence of non-PCI-related bleeding complications over 12 months was comparable between the 2 groups. The cumulative incidence of major cardiovascular events (MACEs) was comparable between the prasugrel and clopidogrel groups (log-rank test; p=0.561). A multivariate logistic regression analysis of the 250 prasugrel-treated patients showed that acute coronary syndrome tended to be negatively associated with the incidence of PCI-related bleeding complications (p=0.061). Conclusion Prasugrel and clopidogrel may have similar efficacy for preventing cardiovascular events as the post-PCI antiplatelet regimen; however, prasugrel should be used cautiously because of the risk of PCI-related bleeding complications.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/etiologia , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ticlopidina/uso terapêutico
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