Background Concomitant use of proton-pump inhibitors (PPIs) has been implicated in diminished antiplatelet response to clopidogrel and an increased risk of ischemic events, but primarily among ...patients undergoing percutaneous coronary intervention. We sought to examine the potential influence of interactions between PPIs and clopidogrel versus prasugrel on platelet reactivity and clinical outcomes after acute coronary syndromes (ACS) in patients managed medically without revascularization. Methods This analysis from the TRILOGY ACS trial focused upon the 7,243 ACS patients aged <75 years who were managed without revascularization, randomized to clopidogrel or prasugrel, and followed for a median of 17 months. Proton-pump inhibitor type and use were assessed at each study visit, and 2,049 of the patients in this cohort underwent serial platelet reactivity assessments. Results Proton-pump inhibitor use (23%) was similar between the clopidogrel and prasugrel groups at baseline and throughout the study. Median on-treatment platelet reactivity values were consistently lower with prasugrel versus clopidogrel irrespective of PPI use. For the primary end point (composite of cardiovascular death, myocardial infarction MI, or stroke), PPI use modified the unadjusted treatment effect of prasugrel versus clopidogrel (interaction P = .02). After adjusting for differences in baseline characteristics, this treatment effect modification was attenuated for the composite end point (interaction P = .06) but was significant for the MI component end point (interaction P = .01). Similarly, among patients on a PPI, the frequency of MI was significantly lower with prasugrel versus clopidogrel (hazard ratio = 0.61; 95% CI 0.42-0.88). These findings were similar by PPI type (omeprazole and pantoprazole). Conclusions Among ACS patients managed without revascularization, use of PPIs did not result in a differential antiplatelet response between prasugrel versus clopidogrel but was associated with a lower incidence of MI with prasugrel. These hypothesis-generating findings suggest that factors besides platelet reactivity may underlie the differential risk of MI observed by treatment assignment with PPI use.
In a randomized trial involving patients with high-risk vascular disease, the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers but was ...not associated with a lower rate of cardiovascular events than placebo.
Pharmacologic reduction of the low-density lipoprotein (LDL) cholesterol level with statins substantially decreases the risks of death and complications from cardiovascular causes.
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Considerable interest has focused on the identification of approaches that might further reduce cardiovascular-event rates among high-risk patients.
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Epidemiologic studies have shown inverse associations between high-density lipoprotein (HDL) cholesterol levels and cardiovascular outcomes,
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a correlation that persists despite treatment with statins.
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Nevertheless, therapeutic interventions that raise the HDL cholesterol level have not been shown to reduce cardiovascular risk.
Cholesteryl ester transfer protein (CETP) modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins.
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This trial compared the efficacy of antiplatelet therapy with prasugrel or clopidogrel in patients with non–ST-segment elevation MI or unstable angina. Although prasugrel provides more intense ...platelet inhibition, clinical outcomes were similar with the two drugs.
Clinical-practice guidelines for patients with acute coronary syndromes consisting of unstable angina or myocardial infarction without ST-segment elevation recommend a strategy of early invasive management (angiography within 48 to 72 hours with provisional revascularization) for patients at moderate to high risk.
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However, analyses from clinical trials and national registries have shown that many such patients are treated medically without revascularization and that such patients have poorer long-term cardiovascular outcomes than those who undergo revascularization.
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Even though patients with acute coronary syndromes who receive only medical therapy have an increased-risk profile, they have been underrepresented in large-scale, contemporary, randomized . . .
BACKGROUND:The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous ...coronary intervention (PCI), and those undergoing elective PCI.
METHODS:Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroupspatients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI.
RESULTS:Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio HR, 0.44 95% CI, 0.28–0.68), patients with ACS treated with PCI (HR, 0.68 95% CI, 0.52–0.89), and patients undergoing elective PCI (HR, 0.82 95% CI, 0.64–1.04; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 95% CI, 0.54–0.92), ACS treated with PCI (HR, 0.88 95% CI, 0.74–1.06), and elective PCI (HR, 0.87 95% CI, 0.72–1.04; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 95% CI, 0.98–2.26), those with ACS treated with PCI (HR, 2.02 95% CI, 1.53–2.67), and those undergoing elective PCI (HR, 1.91 95% CI, 1.48–2.47; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710).
CONCLUSIONS:An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02415400.
BACKGROUND AND PURPOSE—Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) ...determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients.
METHODS—EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD.
RESULTS—A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups.
CONCLUSIONS—In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD.
CLINICAL TRIAL REGISTRATION—URLhttps://www.clinicaltrials.gov. Unique identifierNCT01732822.
Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores ...de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.
Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF.
To identify cardiometabolic risk factors (CMRF) and ...antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender.
CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender.
Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women.
Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.
La enfermedad por coronavirus 2019 (COVID-19) inició como una serie de casos de neumonía de etiología no precisada en Wuhan, Hubei (China), sin embargo, debido a su alta tasa de contagio y el alto ...número de casos diagnosticados, la Organización Mundial de la Salud (OMS) el 11 de marzo de 2020 la declaró pandemia1,2.
To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in a Mexican population.
A six month, treat-to-target, open study was ...conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90mmHg were randomised to either 120mg FMS or 60mg FMS + 12.5mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study.
FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<.0001) and 16.0±14.1 (p<.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, FMS 60mg+HCTZ 12.5mg, or FMS 120mg+HCTZ 12.5mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<90mmHg and an SBP<140mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%).
Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.
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