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1.
Cardiol Ther ; 10(2): 561-568, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34643895

RESUMEN

INTRODUCTION: This prospective pharmacodynamic (PD) study assessed the effect of the sodium-glucose co-transporter-2 inhibitor (SGLT2i), dapagliflozin, on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) (n = 27) who were on maintenance dual antiplatelet therapy (DAPT) of aspirin 81 mg daily, and clopidogrel 75 mg daily were recruited. Platelet function was evaluated with the VerifyNow™ P2Y12 assay (Werfen, Bedford, MA, USA) and assessed prior to initiation of and after 10 days of treatment with dapagliflozin 10 mg once-daily dose regimen. Results were compared with a paired t test. RESULTS: Treatment with dapagliflozin significantly decreased P2Y12 reaction units (PRU) by 20%, (95% confidence interval (CI) 8.5-32.6%, p value 0.002). The mean difference in PRU was 36.70 (95% CI 16.66-56.75). No patients experienced any serious adverse events (SAEs). CONCLUSIONS: Significantly diminished platelet reactivity was observed on dapagliflozin as compared to without dapagliflozin. This dedicated pharmacodynamic study could be potentially informative and applicable for Trinidadian stable CAD patients with T2DM on DAPT. Further studies are required to confirm these exploratory findings. CLINICAL TRIAL REGISTRATION: EDGE ClinicalTrials.gov number NCT04400760.

2.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34281167

RESUMEN

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.


Asunto(s)
Inhibidores del Factor Xa/uso terapéutico , Fibrinolíticos/uso terapéutico , Enfermedad Arterial Periférica/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/uso terapéutico , Terapia Trombolítica , Trombosis/tratamiento farmacológico
3.
J Cardiovasc Pharmacol ; 78(3): 463-473, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34117181

RESUMEN

ABSTRACT: The aim of our study is to assess the impact of anemia, chronic kidney disease, and diabetes mellitus on platelet reactivity (PR) in patients with severe aortic stenosis, both at baseline and after transcatheter aortic valve implantation (TAVI). This study is a prespecified subanalysis of the REAC-TAVI prospective, multicenter trial that included patients pretreated with aspirin + clopidogrel before TAVI. PR was measured at baseline and at 5 different time points after TAVI with the VerifyNow assay (Accriva Diagnostics, San Diego, CA), over a 3-month follow-up period. Patients with high PR (HPR) at baseline, before TAVI (n = 48) were randomized to aspirin + clopidogrel or aspirin + ticagrelor for 3 months, whereas those with normal PR (NPR) (n = 20) were continued on aspirin + clopidogrel. A "raiser response" in PR was defined as an increase in PR units >20% of baseline after TAVI. Patients with HPR before TAVI presented concomitant anemia and chronic kidney disease more frequently than their counterparts with NPR. Anemia and higher body mass index were independently associated with HPR to clopidogrel at baseline. Moreover, anemic patients with baseline HPR who were continued on clopidogrel presented higher PR after TAVI than patients with HPR switched to ticagrelor. All patients with baseline NPR presented a "raiser response" after TAVI, which was nonexistent among patients with HPR managed with ticagrelor. In summary, anemia seems as a relevant factor associated with baseline HPR and higher PR after TAVI in patients with baseline HPR randomized to clopidogrel, whereas ticagrelor proved more effective than clopidogrel at attaining sustained reductions in PR during follow-up, regardless of baseline comorbidities.

4.
Cardiol Ther ; 10(1): 189-199, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33306161

RESUMEN

INTRODUCTION: This prospective pharmacodynamic (PD) study aimed to assess the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) (n = 20) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow™ P2Y12 assay (Instrumentation Laboratory, Massachusetts, USA) and assessed before the initiation of and after 10 days of treatment with empagliflozin 25 mg once daily maintenance dose regimen. Results were compared with a paired t test. RESULTS: The mean P2Y12 reaction units (PRU) on empagliflozin was significantly less than without empagliflozin at baseline (187.35, 95% confidence interval (CI) 155.38-219.32 vs. 217.25, CI 180.60-253.90; p < 0.030). The mean difference in PRU was 29.90 (95% CI 3.17-56.63). No patients experienced any serious adverse events (SAEs). CONCLUSIONS: Significantly attenuated platelet reactivity was observed on empagliflozin as compared to without empagliflozin. This dedicated pharmacodynamic study could be clinically pertinent for Trinidadian patients with stable CAD and T2DM on DAPT. Further studies are required to confirm these exploratory findings. (Funded by the University of the West Indies, St. Augustine; EFFECT). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT04342819.

5.
Rev. esp. cardiol. (Ed. impr.) ; 73(9): 749-757, sept. 2020. tab, graf
Artículo en Español | IBECS | ID: ibc-187648

RESUMEN

La pandemia producida por la infección del nuevo coronavirus SARS-CoV-2, que da lugar a una enfermedad altamente contagiosa (COVID-19), ha producido un colapso de los sistemas sanitarios de todo el mundo. Se ha descrito que estos pacientes sufren un estado inflamatorio que condiciona un alto riesgo trombótico. Sin embargo, apenas hay información sobre cómo abordar el riesgo trombótico, la coagulopatía y el tratamiento anticoagulante de estos pacientes. Por otra parte, incluso los pacientes no infectados por COVID-19 sufren una tremenda influencia en su abordaje habitual por la situación sanitaria actual. El objetivo del presente documento, elaborado por el Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología, es presentar la información disponible y dar unas pautas sencillas de tratamiento con fármacos antitrombóticos


The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy


Asunto(s)
Humanos , Fibrinolíticos/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Virus del SRAS/patogenicidad , Trombosis/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Tromboembolia Venosa/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Trombosis/prevención & control , Anticoagulantes/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Vitamina K/antagonistas & inhibidores , Pandemias , Neumonía Viral/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/fisiopatología , Interacciones Farmacológicas
6.
Cardiol Ther ; 9(2): 493-503, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32766961

RESUMEN

INTRODUCTION: This prospective, pharmacodynamic study aimed to explore the potential applicability of a low-dose ticagrelor regimen in a heterogeneous Trinidadian subpopulation. METHODS: Patients with stable coronary artery disease (n = 25) who were actively treated with dual antiplatelet therapy of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before initiation of and after 14 days of treatment with a low-dose ticagrelor 45 mg twice daily maintenance dose regimen. Results were compared with a paired t test. RESULTS: The mean P2Y12 reaction units (PRU) score on ticagrelor was significantly less compared to that of clopidogrel (50.4, 95% confidence interval (CI) 29-73.9; vs. 149.6, 95% CI 129.4-169.9; p value < 0.001). Of the patients, 4% experienced Medical Research Council class 1 dyspnea, and Bleeding Academic Research Consortium class 1 bleeding on the ticagrelor regimen (one patient each). CONCLUSIONS: Significantly attenuated platelet reactivity was seen on the low ticagrelor maintenance dose as compared to clopidogrel. This dedicated pharmacodynamic study could be applicable and informative for Trinidadian stable coronary artery disease patients. Further studies are required to confirm these exploratory findings.(Funded by the University of the West Indies, St. Augustine). TRIAL REGISTRATION: ClinicalTrials.gov number NCT04206176.

7.
J Invasive Cardiol ; 32(12): 446-452, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32771996

RESUMEN

OBJECTIVES: Ticagrelor has proven more effective than clopidogrel at attaining a maintained suppression of high platelet reactivity (HPR) in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). This study aims to assess the influence of implanted valve type on the degree of platelet reactivity (PR) after TAVI. METHODS: This study is a prespecified analysis of REAC-TAVI, a prospective, multicenter study that included patients on dual-antiplatelet therapy with aspirin and clopidogrel before TAVI. Patients with HPR (n = 48) were randomized to aspirin and clopidogrel or aspirin and ticagrelor for 3 months, while those without HPR (n = 20) were continued on aspirin and clopidogrel. PR was measured 6 hours, 24 hours, 5 days, 30 days, and 90 days after TAVI with VerifyNow assay. Bioprosthetic valves were classified as balloon-expandable valve (BEV), self-expandable valve (SEV), or other. RESULTS: Sixty-eight patients comprising 32 BEVs, 28 SEVs, and 8 other valves were included. Devices were larger and postdilation was more frequent in the SEV group. Follow-up PR was lower in patients treated with ticagrelor vs those treated with clopidogrel at all time points after TAVI, including patients without baseline HPR (P<.001). PR after TAVI was similar in the three groups. Major cardiovascular adverse events, stroke, and hemorrhagic complications were comparable across the different bioprosthesis groups at 4-month follow-up. CONCLUSIONS: The effect of valve type on PR after TAVI is similar across the spectrum of most transcatheter valves. In our sample, ticagrelor achieved a faster and more effective reduction in PR than clopidogrel in patients with HPR undergoing TAVI, irrespective of valve type.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
8.
Rev Esp Cardiol (Engl Ed) ; 73(9): 749-757, 2020 Sep.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32694078

RESUMEN

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Neumonía Viral/tratamiento farmacológico , COVID-19 , Cardiología , Humanos , Pandemias , Selección de Paciente , SARS-CoV-2 , Sociedades Médicas , España
9.
Rev Esp Cardiol ; 73(9): 749-757, 2020 Sep.
Artículo en Español | MEDLINE | ID: mdl-32327870

RESUMEN

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.

10.
Br J Clin Pharmacol ; 86(6): 1052-1061, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31912949

RESUMEN

BACKGROUND: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. METHODS: We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. RESULTS: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). CONCLUSIONS: In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.


Asunto(s)
Síndrome Coronario Agudo , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Sistema de Registros , Ticagrelor/efectos adversos , Resultado del Tratamiento
12.
Cardiol Ther ; : 229-237, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31292901

RESUMEN

INTRODUCTION: This prospective study aimed to determine whether trimetazidine (TMZ) alters the pharmacodynamic (PD) effects of clopidogrel. METHODS: Patients with stable coronary artery disease (SCAD) (n = 24) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before the initiation of and after 14 days of treatment with TMZ. Results were compared using a paired t test. RESULTS: Almost 80% of the study population were of South Asian descent and had diabetes mellitus (DM). P2Y12 reaction units (PRUs) were higher in patients on TMZ (204 ± 56 compared with 174 ± 71 before TMZ, p = 0.005). The average increase in PRU score was 29 (95% confidence interval 8.8-49.7). Before TMZ, the proportion of patients with high on-treatment platelet reactivity (PRU > 208 units) was 25%, which increased to 42% for patients on TMZ. CONCLUSION: Higher platelet reactivity was seen in patients on TMZ, suggesting that TMZ attenuated the PD effects of clopidogrel in this study of a predominantly South Asian diabetic subpopulation. Alternative therapies should be considered and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03603249.

13.
Minerva Med ; 110(5): 410-418, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31081301

RESUMEN

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.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Enfermedad Coronaria/complicaciones , Enfermedad Arterial Periférica/complicaciones , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/complicaciones , Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/mortalidad , Cuidados Posteriores , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Comorbilidad , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Síndrome Metabólico/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Fumar/epidemiología , España , Centros de Atención Terciaria/estadística & datos numéricos , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico
15.
Open Heart ; 6(1): e000841, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30997117

RESUMEN

Objectives: This novel, pilot study aimed to assess the estimated prevalence of high on-treatment platelet reactivity (HPR) in Trinidad and Tobago. Methods: Patients (n=40) who were awaiting elective percutaneous coronary intervention on maintenance dual antiplatelet therapy (DAPT) with aspirin 81 mg daily and clopidogrel 75 mg or loaded at least 48 hours prior were recruited. Platelet reactivity with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, California, USA) was assessed prior to cardiac catheterisation. Results: 60.7% (17/28) of the South Asian (Indo-Trinidadians) patients had HPR, whereas 14.3% (1/7) of Africans and 40% (2/5) of mixed ethnicity had HPR. There was a significant association between HPR (P2Y12 reaction units >208) and ethnicity with South Asians (Indo-Trinidadians) (OR 5.4; 95% CI 1.18 to 24.66, p=0.029). Conclusions: This pilot study serves to introduce the preliminary observation that the estimated prevalence of HPR is considerably higher within the heterogeneous population in Trinidad at 50% as compared with predominantly Caucasian studies. Furthermore, the HPR is significantly higher in South Asians (Indo-Trinidadians) (>60% of patients) which has severe clinical repercussions considering the cardiovascular disease pandemic. Clopidogrel may not be a satisfactory or optimal antiplatelet agent in this subgroup, and therefore, another more potent antiplatelet such as ticagrelor should be used instead. Further large-scale studies are imperative to confirm these findings. (Funded by the University of the West Indies, St. Augustine; POINT ClinicalTrials.gov number, NCT03667066.).

16.
Thromb Res ; 175: 95-101, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30738371

RESUMEN

INTRODUCTION: There is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrelor-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y12 antagonists in a contemporary real-world population. MATERIALS AND METHODS: This PD study included 988 patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and receiving dual therapy with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor). Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12 assay, multiple electrode aggregometry and vasodilator-stimulated phosphoprotein (VASP) assay. RESULTS: Clopidogrel-treated patients (n = 324) had greater platelet reactivity than those receiving ticagrelor (n = 469) or prasugrel (n = 195) at both time points (p < 0.001 for all comparisons). No difference between ticagrelor and prasugrel was observed at day 1 with the VerifyNow P2Y12 assay (51.5 ±â€¯2.8 vs. 42.7 ±â€¯3.5 PRUs; p = 0.298), whereas ticagrelor achieved greater platelet inhibition at day 30 (48.1 ±â€¯2.5 vs. 89.2 ±â€¯4.2 PRUs; p < 0.001). Similar results were obtained with the VASP assay. Both prasugrel and ticagrelor had markedly lower HPR rates than clopidogrel and very high rates of LPR at both time points. CONCLUSIONS: Prasugrel and ticagrelor displayed more potent and consistent PD effects than clopidogrel in ACS patients undergoing PCI, with a trend towards greater platelet inhibition with ticagrelor during the maintenance phase of therapy compared to prasugrel.


Asunto(s)
Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/métodos , Pruebas de Función Plaquetaria/métodos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Antagonistas del Receptor Purinérgico P2Y/farmacología
17.
JACC Cardiovasc Interv ; 12(1): 22-32, 2019 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-30621974

RESUMEN

OBJECTIVES: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. BACKGROUND: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. METHODS: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. RESULTS: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. CONCLUSIONS: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066).


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Clopidogrel/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticagrelor/administración & dosificación , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Aspirina/efectos adversos , Plaquetas/metabolismo , Clopidogrel/efectos adversos , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Sistema de Registros , España , Ticagrelor/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
18.
J Clin Pharmacol ; 59(2): 295-302, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30207603

RESUMEN

Chronic kidney disease (CKD) is associated with worse clinical outcomes in patients with acute coronary syndrome. However, they are underrepresented in clinical trials. We aimed to investigate differences in prognosis of acute coronary syndrome patients with and without CKD, focusing on the use of novel P2Y12 receptor inhibitors. This multicenter registry involved patients with acute coronary syndrome from 3 tertiary institutions. After excluding anticoagulated patients and patients on antiplatelet monotherapy, 1280 patients remained. During 1 year of follow-up, we recorded all major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke), bleeds (Bleeding Academic Research Consortium classification) and deaths. Of 1280 patients, 325 (25.4%) had CKD; 55.5% of non-CKD patients and 22.7% of CKD patients were prescribed novel P2Y12 inhibitors. During follow-up, CKD patients under novel P2Y12 inhibitors showed a not statistically significant lower mortality and incidence of thrombotic events than clopidogrel-treated ones. In contrast, non-CKD patients taking novel P2Y12 inhibitors had better outcomes in terms of major adverse cardiovascular events (4.72 vs 9.41; P = .006), all-cause mortality (1.32 vs 4.24; P = .006), and severe bleeding events (Bleeding Academic Research Consortium 3-5) (0.94 vs 2.82; P = .030), without differences for any bleeding (8.11 vs 8.47; P = .849). Bleeding risk was not increased by using third-generation P2Y12 inhibitors in either group of patients. In conclusion, the use of third-generation P2Y12 inhibitors among non-CKD patients was associated with better outcomes. CKD patients receiving third-generation P2Y12 inhibitors treatment showed no statistically significant lower mortality and thrombotic events. Bleeding risk was not increased with the use of third-generation P2Y12 inhibitors in either group of patients.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Anciano , Clopidogrel/uso terapéutico , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Pronóstico
20.
Rev. esp. cardiol. (Ed. impr.) ; 71(7): 553-564, jul. 2018. tab, graf
Artículo en Español | IBECS | ID: ibc-178581

RESUMEN

En los últimos años, el número de pacientes anticoagulados y antiagregados está aumentando significativamente. Al ser un tratamiento crónico, es de esperar que a lo largo de su vida necesiten un procedimiento quirúrgico o intervencionista que pueda requerir la interrupción del fármaco antitrombótico. La decisión de retirar o mantener dicho tratamiento estará determinada, por un lado, por el riesgo trombótico y, por otro, por el hemorrágico. De la interacción entre estos 2 factores dependerá la actitud ante la anticoagulación y la antiagregación. El objetivo de este documento de consenso, coordinado desde el Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología y certificado por un amplio número de sociedades científicas que participan en el proceso asistencial del paciente durante el periodo perioperatorio o periprocedimiento, consiste en proponer una serie de recomendaciones prácticas y sencillas con el fin de homogeneizar la práctica clínica diaria


During the last few years, the number of patients receiving anticoagulant and antiplatelet therapy has increased worldwide. Since this is a chronic treatment, patients receiving it can be expected to need some kind of surgery or intervention during their lifetime that may require treatment discontinuation. The decision to withdraw antithrombotic therapy depends on the patient's thrombotic risk versus hemorrhagic risk. Assessment of both factors will show the precise management of anticoagulant and antiplatelet therapy in these scenarios. The aim of this consensus document, coordinated by the Cardiovascular Thrombosis Working Group of the Spanish Society of Cardiology, and endorsed by most of the Spanish scientific societies of clinical specialities that may play a role in the patient-health care process during the perioperative or periprocedural period, is to recommend some simple and practical guidelines with a view to homogenizing daily clinical practice


Asunto(s)
Humanos , Trombosis/prevención & control , Fibrinolíticos/administración & dosificación , Anticoagulantes/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Tromboembolia/prevención & control , Periodo Perioperatorio , Privación de Tratamiento , Pautas de la Práctica en Medicina
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