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1.
Biomed Khim ; 70(2): 99-108, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711409

RESUMO

Platelet functional activity was assessed in healthy volunteers (HV, n=92), patients with stable angina pectoris (SA, n=42) and acute coronary syndrome (ACS, n=73), treated with acetylsalicylic acid (ASA) + clopidogrel and ASA + ticagrelor, respectively. In all HV and patients we have compared parameters of platelet aggregation (maximum light transmission and velocity, Tmax and Vmax) and parameters, characterizing exposure of platelet activation markers, evaluated by flow cytometry. HV platelets were activated by 10 µM, 1 µM TRAP, and 20 µM, 5 µM, 2.5 µM ADP; patient platelets were activated by 10 µM TRAP and by 20 µM and 5 µM ADP. Strong and significant correlations between the aggregation and flow cytometry parameters (the r correlation coefficient from 0.4 up to >0.6) most frequently were registered in HV platelet during activation by 1 µM TRAP and in SA patients during platelet activation by 20 µM and 5 µM ADP. However, in many other cases these correlations were rather weak (r < 0.3) and sometimes statistically insignificant. In HV the differences in PAC-1 binding parameters between platelets activated by 10 µM TRAP (the strongest agonist) and all ADP concentrations were negligible (≤ 10%), while CD62P binding (at all ADP concentrations) and LTA parameters for (5 µM and 2.5 µM ADP) were significantly lower (by 40-60%). Antiplatelet therapy in patients decreased all parameters as compared to HV, but to varying extents. For 10 µM TRAP the MFI index for PAC-1 binding (40-50% decrease) and for both ADP concentrations the Tmax values (60-85% decrease) appeared to be the most sensitive in comparison with the other parameters that decreased to a lesser extent. The data obtained indicate a possibility of inconsistency between different LTA and flow cytometry parameters in assessing platelet activity and efficacy of antiplatelet drugs.


Assuntos
Síndrome Coronariana Aguda , Aspirina , Plaquetas , Clopidogrel , Citometria de Fluxo , Inibidores da Agregação Plaquetária , Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Masculino , Aspirina/farmacologia , Aspirina/uso terapêutico , Feminino , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Pessoa de Meia-Idade , Clopidogrel/farmacologia , Idoso , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/sangue , Adulto , Ticagrelor/farmacologia , Ticagrelor/uso terapêutico , Testes de Função Plaquetária/métodos , Ativação Plaquetária/efeitos dos fármacos , Angina Estável/tratamento farmacológico , Angina Estável/sangue , Difosfato de Adenosina/farmacologia
2.
J Am Heart Assoc ; 13(9): e034414, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38700032

RESUMO

BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice. METHODS AND RESULTS: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 (P<0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Intervenção Coronária Percutânea , Guias de Prática Clínica como Assunto , Cloridrato de Prasugrel , Antagonistas do Receptor Purinérgico P2Y , Ticagrelor , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea/tendências , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Masculino , Feminino , Ticagrelor/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , País de Gales , Clopidogrel/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Padrões de Prática Médica/tendências , Inglaterra , Fidelidade a Diretrizes/tendências , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Fatores de Tempo , Resultado do Tratamento
4.
Dtsch Med Wochenschr ; 149(9): 496-501, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38621683

RESUMO

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio/terapia , Fibrinolíticos/efeitos adversos , Aspirina/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Resultado do Tratamento
5.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612792

RESUMO

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.


Assuntos
Síndrome Coronariana Aguda , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Aspirina/uso terapêutico , Plaquetas , Agregação Plaquetária
6.
BMC Med ; 22(1): 148, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561738

RESUMO

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.


Assuntos
Síndrome Coronariana Aguda , Isoindóis , Intervenção Coronária Percutânea , Fenilbutiratos , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Aspirina/efeitos adversos , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Sistema de Registros , Resultado do Tratamento
8.
Thromb Res ; 236: 144-154, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447421

RESUMO

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.


Assuntos
Síndrome Coronariana Aguda , Trombose , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Clopidogrel/uso terapêutico , Fibrinólise , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Estudos Prospectivos , Aspirina/farmacologia , Aspirina/uso terapêutico
9.
J Thromb Thrombolysis ; 57(4): 537-546, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38555552

RESUMO

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.


Assuntos
Síndrome Coronariana Aguda , Cloridrato de Prasugrel , Ticagrelor , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , População do Leste Asiático , Hemorragia Gastrointestinal/etiologia , Hemorragias Intracranianas/etiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Estudos Retrospectivos , Ticagrelor/uso terapêutico , Resultado do Tratamento
10.
Kardiologiia ; 64(2): 80-84, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38462808

RESUMO

Ticagrelor is a potent, direct-acting, and reversible P2Y12­adenosine diphosphate receptor blocker. It has a rapid onset of action and an intense and consistent platelet reactivity inhibition that has been demonstrated to be superior to clopidogrel in decreasing major adverse events in acute coronary syndrome (ACS). Although ticagrelor is well tolerated in ACS patients, it has side effects, such as dyspnea and bradyarrhythmia, as reported in the Platelet Inhibition and Patient Outcomes (PLATO) study. Furthermore, it was reported that ticagrelor's bradyarrhythmic potential was transient and not clinically significant beyond the acute initiation phase. Nor was there a difference in rates of syncope or need for pacemaker insertion during 30 days of follow-up. Here we report a case of ticagrelor associated with Cheyne-Stokes respiration and asystolic ventricular standstill in a patient with ACS who required resuscitation and insertion of a temporary pacemaker.


Assuntos
Síndrome Coronariana Aguda , Ticagrelor , Humanos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Respiração de Cheyne-Stokes/complicações , Respiração de Cheyne-Stokes/diagnóstico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
11.
Cardiovasc Diabetol ; 23(1): 106, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528542

RESUMO

BACKGROUND: This study aimed to investigate the association of sodium-glucose cotransporter 2 inhibitors (SGLT2i) use with cardiovascular (CV) clinical outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS). METHODS: Data of T2D patients hospitalized for ACS at Civil Aviation General Hospital from January 2019 to December 2022 were collected. Based on SGLT2i use or not, patients were stratified as SGLT2i group and SGLT2i-free group. A 1:1 nearest-neighbor propensity score-matched (PSM) was performed to adjust for the confounding factors and facilitate the robust comparisons between groups. The first occurrence of major adverse cardiovascular events (MACE) with 1 year follow-up, which consisted of CV death, all cause death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission, was assessed. Kaplan-Meier analysis and Cox regressions were conducted to evaluate the prognostic significance of SGLT2i use. Subgroup analyses were performed to assess the interaction between subgroups and SGLT2i use. RESULTS: A total of 925 patients were included, and the SGLT2i use increased from 9.9% in 2019 to 43.8% in 2022. 226 pairs were finally matched using the PSM model. During 1 year follow-up period, a total of 110 patients experienced MACE in the matched cohort, with a rate of 24.3%. Survival analyses showed cumulative incidence of MACE, CV death, and heart failure readmission in the SGLT2i group were significantly lower than the SGLT2i-free group. Additionally, the adjusted Cox analyses demonstrated that SGLT2i was associated with a 34.1% lower risk of MACE (HR 0.659, 95% CI 0.487-0.892, P = 0.007), which was primarily driven by a decrease in the risk of CV death by 12.0% (HR 0.880, 95% CI 0.7830.990, P = 0.033), and heart failure readmission by 45.5% (HR 0.545, 95% CI 0.332-0.893, P = 0.016). This MACE preventive benefit was consistent across different subgroups (P interaction > 0.05 for all comparisons). CONCLUSIONS: In T2D patients with ACS, there was a clear increasing trend in SGLT2i use. SGLT2i was associated with a significantly lower risk of MACE, driven by the decrease in the risk of CV death, and heart failure readmission. Our study confirmed real-world use and efficacy of SGLT2i in a general T2D population with ACS.


Assuntos
Síndrome Coronariana Aguda , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Pontuação de Propensão , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
12.
Turk Kardiyol Dern Ars ; 52(2): 116-124, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38465531

RESUMO

OBJECTIVE: Deciding on the optimal duration of dual antiplatelet treatment (DAPT) remains a complex decision. This survey aims to explore the preferences for antiplatelet therapy and the daily routine regarding DAPT duration in coronary artery disease among a group of cardiologists in Türkiye. METHOD: Using an online questionnaire with 38 questions, the preferences of 314 cardiologists were collected. Qualitative descriptive characteristics of the answers received from the participants were examined. RESULTS: Participating cardiologists mostly worked in training and research hospitals (51.59%) and university hospitals (21.66%). Participants primarily favored ticagrelor in patients undergoing PCI with a diagnosis of STEMI and NSTE-ACS (69.75% and 55.73% respectively). Clopidogrel was the most preferred P2Y12 treatment in patients with chronic coronary syndrome (CCS) after PCI (94.90%). Pre-treatment with a loading dose of a P2Y12 receptor inhibitor was administered to 57.01% of patients with NSTE-ACS, irrespective of the planned treatment strategy. In NSTE-ACS patients with low bleeding risk treated with PCI, 83.12% of participants recommended DAPT for 12 months and 14.65% for >12 months. In high-bleeding-risk NSTE-ACS patients treated with PCI, DAPT durations of six months (74.52%), three months (19.75%), and one month (5.73%) were chosen. Among CCS patients treated with PCI without an increased risk of bleeding, 12 months of DAPT was preferred by 68.15% of participants. Most participants (70.70%) were switching to a more potent P2Y12 receptor inhibitor therapy in emergency department clopidogrel-loaded patients with ACS. CONCLUSION: The aim of this survey to capture a snapshot of the preferences of a group of cardiologists in Türkiye regarding DAPT treatment and duration. The responses were both in accordance and in conflict with the current guidelines.


Assuntos
Síndrome Coronariana Aguda , Cardiologistas , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária , Clopidogrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Turquia , Quimioterapia Combinada , Síndrome Coronariana Aguda/tratamento farmacológico , Hemorragia/induzido quimicamente , Resultado do Tratamento
13.
Medicine (Baltimore) ; 103(10): e37416, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457555

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be effective and safe in patients with stable angina and previous myocardial infarction. However, evidence for initiating their use in patients hospitalized with acute coronary syndrome (ACS) is limited. This systematic review and meta-analysis was performed to provide more clinical evidence. METHODS: PubMed, Embase, OVID, Cochrane Library and ClinicalTrials.gov were systematically searched for eligible randomized controlled trials up to March 20, 2023. The risk ratios, standardized mean differences and 95% confidence intervals were calculated for primary and secondary outcomes. The bias risk of the included studies was assessed using the Cochrane RoB 2 criteria. RESULTS: About 8 randomized controlled trials involving 1255 inpatients with ACS were included. PCSK9 inhibitor treatment significantly reduced low-density lipoprotein cholesterol (LDL-C) (SMD -1.28, 95% CI -1.76 to -0.8, P = .001), triglycerides (TG) (SMD -0.93, 95% CI -1.82 to -0.05, P = .03), total cholesterol (SMD -1.36, 95% CI -2.01 to -0.71, P = .001), and apolipoprotein B (Apo B) (SMD -0.81, 95% CI -1.09 to -0.52, P = .001) within approximately 1 month. PCSK9 inhibitor treatment significantly reduced the total atheroma volume (TAV) (SMD -0.33, 95% CI -0.59 to -0.07, P = .012). It also significantly increased minimum fibrous cap thickness (FCT) (SMD 0.41, 95% CI 0.22-0.59, P = .001) in long-term follow-up (>6 months). PCSK9 inhibitor treatment significantly reduced the risk of readmission for unstable angina (RR 0.32, 95% CI 0.12-0.91, P = .032) in short-term follow-up (<6 months). There were no significant differences in all-cause mortality, cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization or heart failure. Only nasopharyngitis (RR 1.71, 95% CI 1.01-2.91, P = .047) adverse events were significantly observed in the PCSK9 inhibitor group. CONCLUSION: Application of a PCSK9 inhibitor in hospitalized patients with ACS reduced lipid profiles and plaque burdens and was well tolerated with few adverse events.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Doenças Cardiovasculares , Infarto do Miocárdio , Humanos , Anticolesterolemiantes/uso terapêutico , Pró-Proteína Convertase 9 , Inibidores de PCSK9 , Síndrome Coronariana Aguda/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , LDL-Colesterol , Infarto do Miocárdio/tratamento farmacológico , Hospitais , Doenças Cardiovasculares/tratamento farmacológico
14.
Acta Cardiol ; 79(2): 224-234, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38456717

RESUMO

AIM: Left atrial (LA) strain, a novel marker of LA function, reliably predicts diastolic dysfunction. SGLT2 inhibitors improve heart failure outcomes, but limited data exists regarding their use in the immediate aftermath of acute coronary syndrome (ACS). We studied the effect of empagliflozin on LA strain in patients with type 2 diabetes (T2D) and ACS. METHODS: Patients with ACS and T2D were identified and empagliflozin was initiated in eligible patients prior to discharge. Patients not initiated on empagliflozin were analysed as a comparator group. A blinded investigator assessed LA strain using baseline and 3-6 month follow-up echocardiograms. RESULTS: Forty-four participants (n = 22 each group) were included. Baseline characteristics and LA strain were similar in the two groups. LA reservoir, conduit and contractile strain increased in empagliflozin group (28.0 ± 8.4% to 34.6 ± 12.2% p < 0.001, 14.5 ± 5.4% to 16.7 ± 7.0% p = 0.034, 13.5 ± 5.2% to 17.9 ± 7.2% p = 0.005, respectively) but remained unchanged in comparison group (29.2 ± 6.7% to 28.8 ± 7.0%, 12.8 ± 4.2% to 13.3 ± 4.7%, 16.7 ± 5.3% to 15.5 ± 4.5%, respectively, p = NS). The difference in change between groups was significant for LA reservoir (p = 0.003) and contractile strain (p = 0.005). CONCLUSION: In patients with ACS and T2D, addition of empagliflozin to standard ACS therapy prior to discharge is associated with improved LA function.


Assuntos
Síndrome Coronariana Aguda , Compostos Benzidrílicos , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Átrios do Coração/diagnóstico por imagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Função Ventricular Esquerda
15.
Indian Heart J ; 76 Suppl 1: S51-S57, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307382

RESUMO

Despite numerous improvements in the management of acute coronary syndrome(ACS), it is a major cause of mortality in India. Lipids play a critical role in pathogenesis of ACS and reduction of lipid parameters plays a pivotal role in secondary prevention. High total cholesterol and high low-density lipoprotein(LDL) are the major lipid abnormalities globally as well as in Indians. Among all the lipid parameters, LDL is the primary target of lipid-lowering therapies across the globe. High-dose statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bempedoic acid are recommended therapies for LDL reduction in ACS patients. Statins have pleiotropic effects on the modulation of thrombogenesis, endothelial dysfunction, and myocardial protection. Multiple randomised controlled trials and meta-analyses have shown that the use of high-dose statin has significant benefits in ACS. LDL reduction goal is < 55 mg/dl or at least 50 % reduction from the baseline regardless of age or gender. Non-fasting LDL should be measured soon after the ACS as it varies minimally with food intake. The first line of therapy after ACS is to advise lifestyle modifications, combination therapy including high-dose statin with ezetimibe, and evaluation after 4-6 weeks of the index event. If the goal is not achieved then PCSK 9 inhibitors or Bempedoic acid should be used in combination with statins and ezetimibe to reduce recurrent ischaemic events. Despite the proven effect of these lipid-lowering therapies, undertreatment is still a big hurdle across the globe. Prohibitive costs, adverse effects, medication non-adherence, variation in health practice in different countries, and clinical inertia to prescribe this medication by physicians are the main reasons for the undertreatment.


Assuntos
Síndrome Coronariana Aguda , Anticolesterolemiantes , Ácidos Dicarboxílicos , Dislipidemias , Ácidos Graxos , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/complicações , LDL-Colesterol , Ezetimiba/uso terapêutico , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Pró-Proteína Convertase 9/uso terapêutico
17.
Neurosci Lett ; 825: 137689, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38401641

RESUMO

PURPOSE: The ischemia-reperfusion (I/R) injury seen in the heart can cause severe damage to essential organs such as the brain. Cannabidiol (CBD) obtained from Cannabis sativa is used today to treat various diseases. This study aimed to demonstrate CBD's neuroprotective and therapeutic properties in rats with brain damage caused by I/R in the heart. MATERIALS: Rats were divided into four groups; sham, I/R, I/R + Prophylactic CBD, and I/R + Therapeutic CBD. End of the experiment, brain tissues were collected for biochemical, histopathological, and genetic examinations. RESULTS: I/R damage increased the number of degenerative neurons, caspase-3 and TNF-α immunoexpression, total oxidant status levels, and oxidative stress index. Both prophylactic and therapeutic CBD administration reduced these increased values. In addition, the relative fold changes of AMPK, PGC-1α, SIRT1, and Bcl 2 decreased in the I/R group, and the relative fold change of Bax increased, which are indicators of ER stress and apoptosis. Both administrations of CBD reversed these genes' relative fold changes. CONCLUSION: CBD can be protective against brain injury caused by cardiac I/R damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.


Assuntos
Síndrome Coronariana Aguda , Canabidiol , Traumatismo por Reperfusão , Ratos , Animais , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/farmacologia , Traumatismo por Reperfusão/patologia
18.
Thromb Res ; 235: 116-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335566

RESUMO

The mechanism underlying thrombus formation in acute coronary syndrome (ACS) involves both platelets and thrombin. While both pathways are targeted in acute care, platelet inhibition has been predominantly administered in the chronic phase, yet thrombin plays a key role in platelet activation and fibrin formation. Among ACS patients, there is also a persistent chronic increase in thrombin generation, which is associated with a higher rate of adverse events. In the setting of post-ACS care with rivaroxaban or vorapaxar, targeting thrombin has been associated with decreased thrombin generation and reduced cardiovascular events, but has been associated with increased bleeding risk. We explored the evidence supporting thrombin generation in the pathophysiology of recurrent events post-ACS and the role of thrombin as a viable therapeutic target. One specific target is factor XI inhibition, which is involved in thrombin generation, but may also allow for the preservation of normal hemostasis.


Assuntos
Síndrome Coronariana Aguda , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/complicações , Trombina/fisiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Hemorragia/tratamento farmacológico
19.
Eur J Clin Pharmacol ; 80(5): 759-770, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38360988

RESUMO

OBJECTIVE: This retrospective study aimed to investigate the potential impact of ticagrelor and clopidogrel treatment on cardiovascular outcomes in patients with anemia and acute coronary syndrome (ACS) and to provide insights into the optimal therapeutic approach for this vulnerable patient population. METHODS: A retrospective research design was employed, involving patients diagnosed with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) between 2014 and 2021. Inclusion criteria required a hemoglobin level below 12 mg/dL and a minimum 12-month P2Y12 inhibitor treatment. Comprehensive clinical, biochemical, and echocardiographic data were collected from the hospital's electronic repository. The primary efficacy endpoint was major adverse cardiovascular events (MACE), encompassing total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke. Major hemorrhage was the primary safety endpoint. Secondary outcomes included total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke, individually. RESULTS: Patients treated with ticagrelor (n = 118) and clopidogrel (n = 538) were compared. No significant difference was observed in major adverse cardiovascular events (MACE) and major bleeding between ticagrelor and clopidogrel treatment groups (MACE: clopidogrel 10.0% vs. ticagrelor 11.0%, p = 0.75; major bleeding: clopidogrel 2.8%, ticagrelor 2.5%, p = 0.88). Patients with hemoglobin levels ≤ 8 mg/dL demonstrated significantly higher MACE and major bleeding rates in the ticagrelor group (p = 0.008 and p = 0.002, respectively). Among patients aged ≥ 75 years, ticagrelor treatment was associated with a higher risk of major bleeding (p = 0.04). CONCLUSIONS: Ticagrelor and clopidogrel exhibited comparable efficacy and safety outcomes in anemic ACS patients over a one-year period. Although ticagrelor demonstrated superiority in reducing ischemic events, it is crucial to recognize the limitations of retrospective studies in informing clinical practice. This study offers valuable insights into tailoring antiplatelet therapy for anemic ACS patients and provides guidance for personalized treatment strategies, acknowledging the hypothesis-generating nature of retrospective analyses.


Assuntos
Síndrome Coronariana Aguda , Anemia , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Síndrome Coronariana Aguda/tratamento farmacológico , Acidente Vascular Cerebral Hemorrágico/induzido quimicamente , Acidente Vascular Cerebral Hemorrágico/tratamento farmacológico , Intervenção Coronária Percutânea/efeitos adversos , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Hemorragia/induzido quimicamente , Anemia/etiologia , AVC Isquêmico/tratamento farmacológico , Hemoglobinas , Resultado do Tratamento , Cloridrato de Prasugrel/uso terapêutico
20.
Clin Drug Investig ; 44(3): 163-174, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38326641

RESUMO

BACKGROUND AND OBJECTIVE: The relationship between hyperuricemia and mortality in patients with acute coronary syndrome (ACS) is considerably controversial. Additionally, the strategy of dual antiplatelet therapy (DAPT) has not been evaluated in patients with ACS with hyperuricemia. This study aims to evaluate the impact of hyperuricemia on the prognosis of ACS and explore the efficacy of ticagrelor compared with clopidogrel in patients with hyperuricemia. METHODS: The study enrolled 4319 patients divided into hyperuricemia (HUA, n = 1060) and normouricemia (NUA, n = 3259) groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox regression analysis was used to evaluate the impact of ticagrelor versus clopidogrel on all-cause and cardiovascular mortality. RESULTS: Hyperuricemia significantly increased the risk of all-cause death compared with patients with NUA at 7 days [adjusted hazard ratio (HR): 4.292, 95% confidence interval (CI) 1.727-10.67]; P = 0.002), 14 days (adjusted HR: 2.871, 95% CI 1.326-6.219; P = 0.0074), 30 days (adjusted HR: 2.168, 95% CI 1.056-4.453; P = 0.035), 3 months (adjusted HR: 2.018, 95% CI 1.152-3.533; P = 0.0144) and 1 year (adjusted HR: 1.702, 95% CI 1.137-2.548; P = 0.009). No significant difference was found between ticagrelor and clopidogrel in 1-year all-cause mortality [7.0% versus 5.5%, adjusted HR: 1.114 (95% CI 0.609-2.037), P = 0.725] among patients with concomitant hyperuricemia. CONCLUSION: Hyperuricemia was independently related to an increased risk of all-cause and cardiovascular death in patients with ACS undergoing PCI. At 1-year follow-up, there were no significant differences between ticagrelor and clopidogrel concerning all-cause and cardiovascular death in patients with hyperuricemia.


Assuntos
Síndrome Coronariana Aguda , Hiperuricemia , Intervenção Coronária Percutânea , Humanos , Clopidogrel/uso terapêutico , Ticagrelor/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Hiperuricemia/complicações , Hiperuricemia/tratamento farmacológico , Resultado do Tratamento
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