RESUMEN

AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS AND RESULTS: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. CONCLUSION: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Asunto(s)

Antiarrítmicos , Flecainida , Bloqueadores de los Canales de Sodio , Humanos , Anciano , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Flecainida/uso terapéutico , Flecainida/efectos adversos , Antiarrítmicos/uso terapéutico , Antiarrítmicos/efectos adversos , Bloqueadores de los Canales de Sodio/uso terapéutico , Bloqueadores de los Canales de Sodio/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Factores de Tiempo , Frecuencia Cardíaca/efectos de los fármacos , Accidente Cerebrovascular

RESUMEN

Aims: Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of aspirin monotherapy, clopidogrel monotherapy, ticagrelor monotherapy, rivaroxaban monotherapy, clopidogrel plus aspirin, ticagrelor plus aspirin, and rivaroxaban plus aspirin in the high-risk ischemic cohorts. Methods and results: Eleven randomized controlled trials were included (n = 111737). The primary outcomes were major cardiovascular and cerebrovascular events (MACEs) and major bleeding. A random effects model was used for frequentist network meta-analysis. Odds ratio (OR) and 95% credible intervals (CI) were reported as a summary statistic. Compared with aspirin monotherapy, rivaroxaban plus aspirin [OR 0.79 (95% CI, 0.69, 0.89)], ticagrelor plus aspirin [0.88 (0.80, 0.98)], clopidogrel plus aspirin [0.56 (0.41, 0.77)] were associated with a reduced risk of MACEs, but rivaroxaban monotherapy [0.92 (0.79, 1.07)], ticagrelor monotherapy [0.68 (0.45, 1.05)], and clopidogrel monotherapy [0.67 (0.43, 1.05)] showed no statistically significant difference. However, rivaroxaban monotherapy and all dual antithrombotic strategies increased the risk of major bleeding to varying degrees, with ticagrelor plus aspirin associated with the highest risk of major bleeding. The net clinical benefit favored clopidogrel or ticagrelor monotherapy, which have a mild anti-ischemic effect without an increase in bleeding risk. Conclusion: The present network meta-analysis suggests that clopidogrel or ticagrelor monotherapy may be recommended first in this cohort of SCVD at high ischemic risk. But clopidogrel plus aspirin or rivaroxaban plus aspirin can still be considered for use in patients with recurrent MACEs.

RESUMEN

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28-4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59-0.72). Calibration for models II-V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59-29.39)) and model V (NRI 20.00% (95%CI 5.59-34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

Asunto(s)

Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Calcificación Vascular , Aorta Torácica , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia

RESUMEN

BACKGROUND AND AIMS: Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. METHODS: In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4-10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. RESULTS: Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (ß-coefficient -0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (ß-coefficients -0.25; 95%CI -0.33,-0.16 and -0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (ß-coefficient -0.17; 95%CI -0.26,-0.07). CONCLUSIONS: Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.

Asunto(s)

Enfermedades Cardiovasculares , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Seguimiento , Estilo de Vida Saludable , Humanos , Inflamación , Factores de Riesgo

RESUMEN

BACKGROUND/AIMS: Several interventions exist for overcoming high platelet reactivity (HPR) on clopidogrel therapy. The goal of this study was to identify strategies that improve inhibition of platelet reactivity in clopidogrel nonresponders with or without loss of function CYP2C19 genotypes, resulting in platelet reactivity similar to that in responders. METHODS: A total of 376 patients with stenting for coronary artery disease underwent platelet function testing in three centers. Blinded platelet function tests were performed after 75 mg daily clopidogrel treatment for 28 days. In total, 183 nonresponders were genotyped, were randomized to four treatment groups with each treatment lasting approximately 28 days, and underwent repeated measurements of platelet reactivity after treatment. RESULTS: With 75 mg of daily clopidogrel, nonresponders had significantly higher HPR than did responders (multiple electrode aggregometry [MEA, arbitrary platelet aggregation unit]: mean, 71.4; 95% confidence intervals [CI], 68.6 to 74.3; and mean, 27.5; 95% CI, 26.0 to 28.9, respectively; p < 0.001). Ticagrelor or ticlopidine treatment in nonresponders resulted in platelet reactivity similar to that in responders in intermediate metabolizers (mean, 24.0; 95% CI, 19.6 to 28.4; p > 0.05; and mean, 30.0; 95% CI, 24.7 to 37.5; p > 0.05, respectively) and poor metabolizers (mean, 23.2; 95% CI, 18.0 to 28.3; p > 0.05; and mean, 30.3; 95% CI, 24.5 to 6.0; p > 0.05, respectively). However, in extensive metabolizers, only ticagrelor treatment showed platelet reactivity similar to that in responders (mean, 26.1; 95% CI, 24.1 to 28.0; p > 0.05). CONCLUSIONS: Among clopidogrel nonresponders with cardiovascular disease on 75 mg daily clopidogrel, ticagrelor resulted in a comparable degree of platelet inhibition in all nonresponders compared with 150 mg daily clopidogrel or triple therapy with clopidogrel and cilostazol, irrespective of phenotype.