Evaluación de intervención de alertas para riesgo cardiovascular por diclofenaco en afiliados al régimen contributivo 2014 -2015

El objetivo fue evaluar la intervención de las alertas en la prescripción de diclofenaco. Estudio observacional, comparativo, post intervención, de un antes después, en pacientes con prescripción de diclofenaco. Se evaluó la intervención de las alertas restrictivas antes y después de su implementación en los pacientes prescritos con diclofenaco y que tenían asociado un diagnóstico de riesgo cardiovascular según CIE 10 o eran mayores de 65 años. Un total de 315.135 transacciones con prescripción de diclofenaco, en 49.355 pacientes promedio mes. El 94,8% (298.674) de las transacciones fueron prescritas por médicos generales.

Planejamento, síntese e avaliação farmacológica de novos compostos 1,2,5-oxadiazol-2-n-óxido úteis como preventivos de aterotrombose

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Síntese, caracterização e avaliação farmacológica de derivados N-acilhidrazônicos para a prevenção de aterotrombose

Atherosclerosis is a chronic inflammatory disease characterized by accumulation of lipid and fibrous components in arterial vessels, giving rise to atheromas. Development of Atheromatou plaques leads to arterial steatosis, triggering ischemic events. Atherotrombosis has a strong correlation with atherosclerosis, where rupture of atheromatous plaques cause release of vessel wall's pro-thrombotic components, activating platelet aggregation and thromosis. Due to the major role played by platelets on thrombus-embolic conditions, drugs that inhibit platelet aggregation demonstrate great relevance for atherothrombosis prevention, reducing patient mortality. Currently, there are a variety of drugs acting on several different targets, preventing platelet activation. However, these therapies demosntrate side effects such as thrombocytopenia, neutropenia, hemorrhage and low oral availability. Thus, the application of molecular modifications such as hybridization can produce novel, more efficient antiplatelet aggregation inhibitors. In this project we describe the synthesis and characterization of novel N-acilhydrazone compounds, acting through multiple mechanisms such as platelet calcium chelation and nitric oxide donation by furoxanic subunits. Furthermore, we demonstrate that such compounds exhibit biological activity in in vivo bleeding time, in vitro antiplatelet aggregation and in vivo antinociceptive assays. Therefore, novel N-acilhydrazone compounds demonstrate potential as antiplatelet drugs for atherothrombosis prevention.

Synthesis and preliminary evaluation of N-oxide derivatives for the prevention of atherothrombotic events

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States

BACKGROUND: Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of 3 atherothrombotic risk factors. METHODS AND RESULTS: We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P=0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. CONCLUSIONS: The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition.

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (? 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required.

The GPVI - Fc Fusion Protein Revacept Reduces Thrombus Formation and Improves Vascular Dysfunction in Atherosclerosis without Any Impact on Bleeding Times

Glycoprotein VI (GPVI) is a key platelet receptor which mediates plaque-induced platelet activation and consecutive atherothrombosis, but GPVI is also involved in platelet-mediated atheroprogression. Therefore, interference in GPVI-mediated platelet activation has the potential to combine short-term and long-term beneficial effects, specificity and safety especially regarding bleeding complications.

Non-coronary atherosclerosis

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.