RESUMO
BACKGROUND: Enhanced platelet reactivity represents one of the major determinants of cardiovascular risk among diabetic patients. The aim of the present study was to evaluate the impact of metformin use on platelet reactivity in diabetic patients receiving dual antiplatelet therapy (DAPT). METHODS: We included diabetic patients treated with DAPT after an acute coronary syndrome or percutaneous coronary intervention. Platelet reactivity was assessed at 30-90 days by Multiple-electrode aggregometry. In an additional cohort of diabetic patients naïve to antiplatelet therapy, we assessed platelet reactivity by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2 (TxB2). RESULTS: We included 219 diabetic patients, 117 (53.4%) treated with metformin. Metformin was associated with younger age (p=0.03), male gender (p=0.02), lower rate of hypertension (p=0.04), active smoker (p=0.002), previous MI (p<0.001) renal failure (p<0.001), fibrinogen (p<0.001) and C-reactive protein (p=0.04), larger use of diuretics (p=0.04) calcium antagonists (p=0.05), better glycemic control (p<0.001) and higher haemoglobin (p=0.003). The prevalence of HAPR did not significantly differ according to hypoglycemic treatment (p=0.73; adjusted OR[95%CI]=5.63[0.42-76], p=0.19). Moreover, no impact of metformin was observed for HRPR (p=0.77; adjusted OR[95%CI]=1.15[0.55-2.4], p=0.71). Among an additional cohort of 42 diabetic patients naïve to antiplatelet therapy, we confirmed no impact of metformin or insulin on aggregation. CONCLUSIONS: Our study found no apparent association in diabetic patients treated with DAPT, between the use of metformin and platelet reactivity or the rate of HPR.
Assuntos
Plaquetas/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Terapia Antiplaquetária Dupla , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Adulto , Idoso , Comorbidade , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/estatística & dados numéricos , Inibidores da Agregação Plaquetária/administração & dosagemRESUMO
: Recent attention has been focused on the regulation of vitamin D metabolism as modulating the cardiovascular benefits of vitamin D. The aim of the current study was to evaluate the functional impact of the genetic polymorphism rs2762939 of CYP24A1, the hydroxylase-enzyme modulating the inactivation of vitamin D, on the prevalence and extent of coronary artery disease (CAD).A consecutive cohort of patients undergoing coronary angiography in a single centre was included. Significant CAD was defined as at least one stenosis more than 50%, severe CAD as left main and/or three-vessel disease. Among 1204 patients, 673 (55.8%) carried the C allele. Baseline features showed a lower use of beta-blockers among the C-carriers (Pâ=â0.01) and higher levels of C-reactive protein (Pâ=â0.05). The prevalence of CAD and severe CAD was not conditioned by CYP24A1 genetic status [78.7%-GG vs. 81.2%-C-carriers; Pâ=â0.31; adjusted odds ratio (95% confidence interval )â=â0.71(0.20-2.56), Pâ=â0.60 and 29.1%-GG vs. 29.5%-C carriers Pâ=â0.95; adjusted odds ratio (95% confidence interval)â=â0.87 (0.73-1.04), Pâ=â0.13, respectively]. Coronary calcifications were significantly higher among GG homozygotes (Pâ=â0.005). This study showed that the polymorphisms rs2762939 of CYP24A1 is not associated with the prevalence and extent of CAD. However, the C-allele carriage significantly lowers the rate of coronary calcifications.
Assuntos
Doença da Artéria Coronariana/genética , Vitamina D3 24-Hidroxilase/genética , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos ProspectivosRESUMO
BACKGROUND: Acute coronary syndromes (ACS) represent a context of higher thrombotic risk, where larger advantages have been achieved by the administration of dual antiplatelet therapy (DAPT). However, the indication of 1â¯year DAPT after coronary angioplasty for ACS has been supported by an outdated randomized trial (PCI-CURE). In addition, the initial fear of late thrombotic events emerged with first generation drug-eluting stents (DES), that suggested the need of a prolonged DAPT prescription, has been completely overcome by the recent technological evolution of DES, that have shown faster re-endothelization and lower rates of late thrombotic complications. By keeping in mind the balance between thrombotic and bleeding complications, and due to the paucity of dedicated randomized trials, the identification of the optimal duration of DAPT after ACS is still matter of debate, and is therefore the aim of the present meta-analysis. METHODS: Literature and main scientific session abstracts were searched. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. A pre-specified analysis was conducted according to the DAPT strategy allocation (<12 vs standard 12â¯months duration and 6-12â¯months vs extended DAPT). RESULTS: We included 3 RCTs and subanalyses from 8 RCTs, with a total of 17,941 patients. No difference in mortality was observed between shorter vs longer DAPT (OR[95%CI]â¯=â¯1.11[0.90,1.36], pâ¯=â¯0.33; phetâ¯=â¯0.76). A shorter DAPT duration significantly reduced the rate of major bleeding events (1.5%, vs 1.9%, OR [95%CI]â¯=â¯0.75 [0.60, 0.94], pâ¯=â¯0.01; phetâ¯=â¯0.43). The reduction in bleeding events was more significant in trials evaluating extended DAPT duration (OR[95%CI]â¯=â¯0.62[0.45, 0.85], pâ¯=â¯0.003; phetâ¯=â¯0.49). No difference in cardiovascular mortality, myocardial infarction and stent thrombosis was observed with shorter vs standard 12-moth DAPT, whereas a more extended treatment (beyond 1â¯year), was associated with a significant reduction in recurrent ischemic events. Similar results were observed at a sensitivity analysis conducted according to the type of stent, time to randomization or DAPT duration. CONCLUSIONS: Based on the current meta-analysis including 17,941 ACS patients undergoing PCI, a short duration of DAPT may be safely considered, with similar rates of recurrent thrombotic complications as compared to the standard 12â¯months, and similar mortality. A more extended DAPT administration (beyond 1â¯year) provides benefits in ischemic events, but with an excess in haemorragic complications, with overall neutral effects on mortality.
Assuntos
Síndrome Coronariana Aguda/terapia , Hemorragia , Inibidores da Agregação Plaquetária/farmacologia , Síndrome Coronariana Aguda/mortalidade , Esquema de Medicação , Quimioterapia Combinada/métodos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Intervenção Coronária Percutânea/métodos , Risco Ajustado , Fatores de TempoRESUMO
Vitamin D deficiency has been implicated in the progression of atherosclerosis and acute thrombotic events. We aimed at evaluating the impact of vitamin D deficiency on periprocedural myocardial infarction (PMI) in patients undergoing percutaneous coronary interventions (PCI). We included 934 patients undergoing non-urgent PCI. Assessment of myocardial biomarkers was performed from 6 to 48â¯h after PCI. PMI was defined as Creatine Kinase-MB increase by 3 times the Upper Limit Normal or by 50% of an elevated baseline value, periprocedural myocardial damage as Troponin I increase by 3â¯×â¯ULN or 50% of baseline. Patients were divided according to vitamin D tertiles values (<10.2â¯ng/ml; 10.2-18.7â¯ng/ml; ≥18.8â¯ng/ml). Lower tertiles values of vitamin D were associated with age (pâ¯=â¯0.04), female gender, (pâ¯=â¯0.001), and a higher cardiovascular risk profile. Lower vitamin D levels related with PCI of descending anterior coronary artery or bypass vein grafts (pâ¯=â¯0.03), treatment of bifurcations (pâ¯=â¯0.05) and side branch loss (pâ¯=â¯0.05) and inversely with direct stenting (pâ¯=â¯0.002). However, lower vitamin D levels did not influence the risk of PMI (adjusted OR [95% CI]â¯=â¯0.81[0.65,1.18], pâ¯=â¯0.09) or periprocedural myocardial damage (adjusted OR [95% CI]â¯=â¯0.93[0.77,1.13], pâ¯=â¯0.48). Similar results were achieved when considering the severity of vitamin D deficiency. Therefore, in patients undergoing PCI, no association was observed between vitamin D deficiency and the risk of periprocedural MI and myocardial damage.