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1.
Expert Opin Investig Drugs ; 29(1): 33-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31869253

RESUMO

Introduction: Despite current guideline-based, secondary prevention strategies in patients with the acute coronary syndrome, the residual ischemic risk is still at an unacceptable rate, and there is a concomitant high bleeding event rate. These observations mandate investigations of novel treatment strategies to meet the unmet need to improve outcomes in patients with ACS.Areas covered: In this review, the author(s) focus on new agents with ongoing or recently completed phase II trials for the treatment of ACS. We searched MEDLINE and clinicaltrials.org for Phase II trials in ACS patients, and important original investigations are reviewed.Expert opinion: Some of the novel drugs evaluated in the Phase II trials hold promise for future therapies such as AZD5718, anakinra, tocilizumab, CSL112, MEDI 6102, inclisiran, PZ128, selatogrel, and RVX-208. Their efficacy and safety should be evaluated in large scale Phase III trials. The higher cost of the drug will be a major limitation for wide-spread use of novel agents in general practice in future.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Desenvolvimento de Medicamentos , Drogas em Investigação/farmacologia , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/prevenção & controle , Animais , Ensaios Clínicos Fase II como Assunto , Drogas em Investigação/efeitos adversos , Humanos , Guias de Prática Clínica como Assunto , Prevenção Secundária/métodos
2.
Angiology ; 71(3): 235-241, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31867981

RESUMO

Optimal medical therapy (OMT) at discharge is recommended after acute coronary syndrome (ACS). Few studies report the impact of OMT on long-term clinical outcome in a real-world scenario. We evaluated the impact of discharge OMT on top of dual-antiplatelet therapy (DAPT) on clinical outcome in the real-world ACS population of the Survey on anTicoagulated pAtients RegisTer ANTIPLATELET registry. The primary end point was major adverse cardiac and cerebrovascular event (MACCE), a composite of death, myocardial infarction, stroke, or target vessel revascularization. The co-primary end point was net adverse cardiac and cerebrovascular event (NACE), based on MACCE plus major bleeding. Consecutive patients with ACS with 1-year follow-up were enrolled. They were evaluated at discharge for the use of a ß-blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and statins. Optimal medical therapy was defined as the use of ≥2 of 3 medications. At multivariate analysis, both MACCE and NACE were significantly higher in non-OMT patients than in OMT patients (MACCE 18 [19] vs 59 [9], hazard ratio [HR] = 0.44 [0.26-0.75], P = .002, NACE 19 [20] vs 67 [10], HR = 0.47 [0.28-0.79], P = .004). In this real-world scenario, OMT at discharge on top of DAPT seems associated with a better clinical outcome compared with patients discharged on non-OMT.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Sistema de Registros , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
3.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(12): 985-992, 2019 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-31877595

RESUMO

Objective: To observe the use of clopidogrel and related factors for patients with acute coronary syndrome (ACS) in terms of early use, loading dose, dual antiplatelet therapy (DAPT) and maintenance dose hospitalized in non-PCI country hospitals in China. Methods: Patients hospitalized for ACS from 101 non-PCI country hospitals across China were recruited prospectively from October 2011 to November 2014. In-hospital clopidogrel use rate, the proportions of early use (within 24 hours), loading dose use (≥300 mg), DAPT (early use combined with aspirin) and maintenance dose use (following dose≥75 mg/d) were analyzed. Generalized estimated equation (GEE) model was used to explore factors associated to in-hospital clopidogrel use and loading dose use in both univariate and multivariate analyses, adjusting for cluster effect. Results: A total of 14 809 ACS patients were included, with an average age of (64.1±11.6) years and 60% (8 888/14 809) were male. The in-hospital clopidogrel use rate was 66.4% (9 828/14 809), which varied across different regions, years and sub-types of ACS (all P<0.05). Among users, the proportions of patients with early use, DAPT and maintenance dose use were 91.3% (8 734/9 562), 89.2% (8 526/9 562) and 95.1% (9 094/9 562), respectively, but the proportion of patients received loading dose was only 41.8% (3 995/9 562). Multivariate analyses showed that patients who admitted to hospital in earlier years and with non-ST elevation ACS, ≥75 years old, female, non-smoking, illiterate, heart rate≥100 beats per minute, atrial fibrillation, not on ECG monitoring, and not using other anti-ACS drugs were less likely to receive clopidogrel (all P<0.05). And those clopidogrel users who with non-ST elevation ACS, ≥75 years old, non-smoking, illiterate, not using other anti-ACS drugs were less likely to receive loading dose (all P<0.05). Conclusion: The use rate of clopidogrel and the loading dose among in-hospital ACS patients are both low and remain to be improved in non-PCI county hospitals in China. Special attention should be paid on non-ST elevation ACS, ≥75 years old, female, and illiterate patients to increase the rational use of clopidogrel and the loading dose.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , China , Feminino , Hospitais de Condado , Humanos , Masculino , Pessoa de Meia-Idade
4.
Tex Heart Inst J ; 46(3): 203-206, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31708704

RESUMO

The platelet aggregation inhibitor ticagrelor, a P2Y12 receptor antagonist, is widely used after angioplasty in patients with acute coronary syndrome. Clinical trial data have shown that it is well tolerated by most patients. We present the case of a 62-year-old woman whose ticagrelor-related asymptomatic and persistent sinus pauses after angioplasty resolved when ticagrelor was replaced with prasugrel.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Angioplastia Coronária com Balão/métodos , Parada Cardíaca/induzido quimicamente , Complicações Pós-Operatórias , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Eletrocardiografia , Feminino , Parada Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos
5.
Int Heart J ; 60(6): 1284-1292, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735782

RESUMO

The efficacy of pre-procedural beta-blocker use in patients with acute coronary syndrome (ACS) is not well established in the current percutaneous coronary intervention (PCI) era. We investigate the effect of pre-procedural beta-blocker use on clinical outcomes in patients with ACS undergoing PCI. Among 44,967 consecutive cases of PCI enrolled in the nationwide, retrospective, multicenter registry (K-PCI registry), 31,040 patients with ACS were selected and analyzed. We classified patients into pre-procedural beta-blocker group (n = 8,678) and pre-procedural no-beta-blocker group (n = 22,362) according to the use of beta-blockers at least for two weeks before index PCI. Propensity score-matching analysis was performed and resulted in 7,445 pairs. The primary outcome was in-hospital cardiac death. In propensity score-matched populations, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death compared with the pre-procedural no-beta-blocker group (1.1% versus 2.0%, unadjusted odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.42-0.73, P < 0.01). In subgroup analysis, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death, compared with the pre-procedural no-beta-blocker group in ST-segment elevation myocardial infarction subpopulation (3.1% versus 6.1%, unadjusted OR: 0.49, 95% CI: 0.34-0.71, P < 0.01) and non-ST-segment elevation myocardial infarction subpopulation (1.5% versus 2.9%, unadjusted OR: 0.51, 95% CI: 0.33-0.79, P < 0.01). However, in unstable angina subpopulation, the in-hospital cardiac death rate was comparable between both groups. In conclusion, the use of pre-procedural beta-blocker was associated with a lower risk of in-hospital cardiac death in patients with ACS undergoing PCI. This result adds to the body of evidence that use of pre-procedural beta-blocker in patients with ACS might be reasonable.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Antagonistas Adrenérgicos beta/administração & dosagem , Intervenção Coronária Percutânea , Pré-Medicação , Cuidados Pré-Operatórios , Síndrome Coronariana Aguda/mortalidade , Idoso , Esquema de Medicação , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
6.
Expert Opin Drug Saf ; 18(12): 1171-1189, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31623473

RESUMO

Introduction: Potent platelet inhibition reduces the risk of thrombotic complications including myocardial infarction and death in patients with acute coronary syndrome (ACS). Targeting different pathways involved in thrombotic processes have synergistic effects and more effectively counteract thrombosis both in the acute and long-term following an ACS. Unavoidably, more potent platelet inhibition increases the risk of bleeding. In light of the adverse prognostic implications associated with bleeding, including increased mortality, safety aspects with antiplatelet therapy have gained increased importance.Areas covered: This review aims at describing the safety of different antiplatelet agents, particularly with regards to the risk of bleeding complications, used in the management of ACS patients. New bleeding reduction strategies to enhance the safety of antiplatelet therapy are also reviewed.Expert opinion: The final goal of a well-structured antiplatelet treatment strategy is that of tackling the spectrum of ischemic risk without compromising patient safety. A simple mnemonic rule for guiding therapeutic decisions in this complex clinical scenario can be summarized with the acronym 'ABC', meaning the sequential process of assessing, balancing and customizing treatment strategies in individual patients on the tradeoff between bleeding and ischemic risk. This approach is recommended for maximizing the ischemic benefits, while preserving safety, with the use of antiplatelet therapy.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Síndrome Coronariana Aguda/complicações , Hemorragia/epidemiologia , Hemorragia/prevenção & controle , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem , Trombose/etiologia , Trombose/prevenção & controle
7.
Expert Opin Drug Saf ; 18(12): 1119-1125, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580164

RESUMO

Introduction: The non-vitamin K antagonist oral anticoagulants (NOACs) are changing the landscape for stroke prevention in atrial fibrillation (AF) and prevention or treatment of venous thromboembolism (VTE). In patients with AF and concomitant acute coronary syndrome (ACS), the treatment regimen of combined NOACs and P2Y12 inhibitors is gaining popularity.Areas covered: We conducted a review of safety evaluation and effectiveness of apixaban for AF and ACS treatment, both alone and in combination with different antiplatelet treatment regimens. The aim was to provide an overview of apixaban including mechanism of action, indications, adverse events and tolerability.Expert opinion: Apixaban is recommended as a safe, well tolerated and effective oral anticoagulant for reducing the risk of ischemic events among AF patients. It is of value in prevention and treatment of VTE and pulmonary embolism. Comparing to VKA, apixaban was superior in preventing stroke or systemic embolism with lower major bleeding events among AF patients. When combined with dual antiplatelet therapy apixaban may cause dose-related increase in bleeding which reduces the benefit of this treatment regimen among ACS patients but without AF. In those with ACS and concomitant AF, the combination of apixaban with P2Y12 inhibitor appears to be safe and effective.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Síndrome Coronariana Aguda/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Humanos , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
8.
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
9.
Ther Adv Cardiovasc Dis ; 13: 1753944719863641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364490

RESUMO

BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS: A post hoc exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no versus yes)]. CONCLUSIONS: The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Isquemia Encefálica/mortalidade , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
10.
Nutrients ; 11(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349559

RESUMO

(1) Background: the composition of high-density lipoproteins (HDL) becomes altered during the postprandial state, probably affecting their functionality vis-à-vis the endothelium. Since acute coronary syndrome (ACS) in women is frequently associated with endothelial dysfunction, it is likely that HDL are unable to improve artery vasodilation in these patients. Therefore, we characterized HDL from women with ACS in fasting and postprandial conditions. We also determined whether microencapsulated pomegranate (MiPo) reverts the HDL abnormalities, since previous studies have suggested that this fruit improves HDL functionality. (2) Methods: Eleven women with a history of ACS were supplemented daily with 20 g of MiPo, for 30 days. Plasma samples were obtained during fasting and at different times, after a lipid load test to determine the lipid profile and paraoxonase-1 (PON1) activity. HDL were isolated by sequential ultracentrifugation to determine their size distribution and to assess their effect on endothelial function, by using an in vitro model of rat aorta rings. (3) Results: MiPo improved the lipid profile and increased PON1 activity, as previously reported, with fresh pomegranate juice. After supplementation with MiPo, the incremental area under the curve of triglycerides decreased to half of the initial values. The HDL distribution shifted from large HDL to intermediate and small-size particles during the postprandial period in the basal conditions, whereas such a shift was no longer observed after MiPo supplementation. Consistently, HDL isolated from postprandial plasma samples hindered the vasodilation of aorta rings, and this endothelial dysfunction was reverted after MiPo consumption. (4) Conclusions: MiPo exhibited the same beneficial effects on the lipid profile and PON1 activity as the previously reported fresh pomegranate. In addition, MiPo supplementation reverted the negative effects of HDL on endothelial function generated during the postprandial period in women with ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lipoproteínas HDL/sangue , Extratos Vegetais/administração & dosagem , Período Pós-Prandial , Triglicerídeos/sangue , Vasodilatação/efeitos dos fármacos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Administração Oral , Adulto , Animais , Arildialquilfosfatase/sangue , Biomarcadores/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Frutas , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipolipemiantes/efeitos adversos , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Ratos Wistar , Fatores de Tempo , Resultado do Tratamento
12.
BMJ ; 365: l2222, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253632

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Relevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu. REVIEW METHODS: Randomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events. RESULTS: 17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results. CONCLUSIONS: In patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099519.


Assuntos
Clopidogrel/uso terapêutico , Stents Farmacológicos/normas , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/epidemiologia , Trombose/mortalidade
13.
Biomarkers ; 24(6): 517-523, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31215825

RESUMO

To evaluate whether genotype-guided antiplatelet therapy reduces the rates of cardiovascular events and bleeding events in patients with acute coronary syndrome (ACS). We systematically searched Pubmed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) (searched in September 2018) for controlled studies evaluating genotype-guided antiplatelet therapy in ACS with percutaneous coronary intervention (PCI) or without PCI. The primary endpoint was a composite of death, myocardial infarction (MI), stroke, targeted vessel revascularization and/or major bleeding. A total of five studies involving 2900 patients were included. Compared with the conventional group, the genotype-guided group had a decreased risk of primary composite outcomes (RR= 0.54; 95% CI: 0.41-0.72; I2 = 30%), death (RR = 0.54; 95% CI: 0.32-0.94; I2 = 21%), MI (RR = 0.52; 95% CI: 0.31-0.88; I2 = 49%), targeted vessel revascularization (RR = 0.59; 95% CI: 0.35-0.98; I2 = 0%), but not for stroke (RR = 0.53; 95% CI: 0.22-1.24; I2 = 0%) and bleeding events (RR = 0.80; 95% CI: 0.51-1.25; I2 = 33%). Genotype-guided strategies could reduce the rates of cardiovascular events without increasing bleeding events compared with conventional treatment in ACS. Future multi-centre genotype-based randomized control trials are required to confirm these findings.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Hemorragia/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/tratamento farmacológico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/mortalidade , Aspirina/uso terapêutico , Plaquetas , Revascularização Cerebral/métodos , Clopidogrel/uso terapêutico , Expressão Gênica , Genótipo , Hemorragia/etiologia , Hemorragia/genética , Hemorragia/mortalidade , Humanos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida , Trombose/complicações , Trombose/genética , Trombose/mortalidade
14.
Chem Pharm Bull (Tokyo) ; 67(5): 419-425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061366

RESUMO

Patients with type 2 diabetes (T2DM) and hyperlipidemia are with high risk of myocardial infarction (MI) or coronary death events. The combined use of ezetimibe and atorvastatin could improve treatment efficacy and safety. To explore the efficacy and safety of ezetimibe in combination with atorvastatin for the treatment of patients with T2DM and acute coronary syndrome (ACS). This was a non-randomized cohort study of 95 consecutive, treatment-naïve patients with T2DM and ACS treated at the Quanzhou First Hospital of Fujian Province between February 2014 and March 2016. According to the treatment strategy they selected, the patients were categorized into the atorvastatin (n = 46) and atorvastatin + ezetimibe (n = 49) groups. The patients were followed up at 2 weeks and 12 months. The primary endpoints included the incidence of adverse cardiovascular events and changed in blood lipids and high-sensitivity C-reactive protein (hs-CRP). At 12 months, serum total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower, and high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in the atorvastatin + ezetimibe (EZ) group than in the atorvastatin group (all p < 0.05). The LDL-C control rate at 12 months was significantly higher in the atorvastatin + EZ group compared with the atorvastatin group (p = 0.006). Seven patients in the atorvastatin group were re-hospitalized for angina pectoris, while only one patient in the atorvastatin + EZ group was re-hospitalized for angina pectoris (p = 0.02). The efficacy of atorvastatin + EZ in treating T2DM patients accompanied with ACS was significantly higher than using atorvastatin alone. This combined strategy has good safety profile, and could be recommended for clinical application.


Assuntos
Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Ezetimiba/uso terapêutico , Síndrome Coronariana Aguda/sangue , Anticolesterolemiantes/efeitos adversos , Atorvastatina/efeitos adversos , Proteína C-Reativa/análise , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Ezetimiba/efeitos adversos , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/enzimologia
15.
Thromb Haemost ; 119(7): 1037-1047, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079416

RESUMO

Oral P2Y12 receptor inhibitors represent a mainstay treatment in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. In the setting of ST-elevation myocardial infarction, when early platelet inhibition is highly desirable, the onset of action of oral P2Y12 receptor inhibitors is, however, delayed, likely due to delayed drug absorption. Crushing the tablets, which are to be used for patient loading with an oral P2Y12 receptor inhibitor, has been shown to provide earlier platelet inhibition than standard, integral tablets administration. Chewed ticagrelor tablets may also result in a similar effect. Such findings should be interpreted with caution, mainly due to the small number of patients enrolled and the nature (pharmacodynamic/pharmacokinetic) of the respective studies. Furthermore, in patients with out-of-hospital cardiac arrest, who remain comatose, crushing tablets is commonly applied in clinical practice for platelet P2Y12 receptor inhibition. In this review, we focus on current evidence regarding the role of crushed P2Y12 receptor inhibitor pills, analyzing clinical scenarios where most of the promise exists along with future expectations from this type of formulation. Large randomized studies are needed to draw firm conclusions regarding the clinical benefit of 'crushing' over the usual 'not-crushing' practice.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/fisiologia , Composição de Medicamentos/métodos , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/cirurgia , Plaquetas/efeitos dos fármacos , Humanos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Comprimidos , Ticagrelor/farmacologia
16.
Minerva Med ; 110(5): 410-418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31081301

RESUMO

BACKGROUND: Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios. METHODS: This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed. RESULTS: NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively). CONCLUSIONS: New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Doença das Coronárias/complicações , Doença Arterial Periférica/complicações , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/complicações , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Assistência ao Convalescente , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Comorbidade , Uso de Medicamentos/estatística & dados numéricos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fumar/epidemiologia , Espanha , Centros de Atenção Terciária/estatística & dados numéricos , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
17.
Eur J Clin Pharmacol ; 75(8): 1059-1068, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081522

RESUMO

PURPOSE: High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR. METHODS: In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days. RESULTS: The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%-91.70%] vs. 44.25% [34.67%-79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events. CONCLUSIONS: In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Clopidogrel/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Ticagrelor/efeitos adversos , Resultado do Tratamento
18.
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
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(5): 351-359, 2019 May 24.
Artigo em Chinês | MEDLINE | ID: mdl-31142078

RESUMO

Objective: To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China. Methods: Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported. Results: A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin. Conclusion: In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Aterosclerose/tratamento farmacológico , China , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino
20.
Medicine (Baltimore) ; 98(14): e15106, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946377

RESUMO

INTRODUCTION: Coronary bifurcations are encountered in about 15% to 20% of percutaneous coronary interventions (PCIs). They are considered technically challenging and associated with worse clinical outcomes than nonbifurcation lesions. The BiOSS LIM C is a dedicated bifurcation balloon expandable stent made of cobalt-chromium alloy (strut thickness 70 µm) releasing sirolimus (1.4 µg/mm) from the surface of a biodegradable coating comprised of a copolymer of lactic and glycolic acids. CONCLUSION: The aim of the randomized, multicenter, open-label, controlled POLBOS III trial is to compare BiOSS LIM C with limus second-generation drug-eluting stents (DES) in the treatment of non-left main stem coronary bifurcations (ClinicalTrials.gov NCT03548272).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Estenose Coronária/tratamento farmacológico , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents Metálicos Autoexpansíveis , Síndrome Coronariana Aguda/terapia , Cromo , Cobalto , Estenose Coronária/terapia , Humanos , Estudos Multicêntricos como Assunto , Projetos de Pesquisa , Sirolimo/administração & dosagem , Resultado do Tratamento
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