Use Of Antiplatelet Drugs Research Articles

P1576Association of colorectal cancer with genetic and epigenetic variation in PEAR1 - a population-based cohort study

Abstract Background Platelet Endothelial Aggregation Receptor 1 (PEAR1) modulates angiogenesis and platelet contact-induced activation, which play a role in the pathogenesis of colorectal cancer. Purpose To study the association of colorectal cancer with genetic and epigenetic variation in PEAR1. Methods Among 2532 randomly recruited participants enrolled in the family-based Flemish Study on Environment, Genes and Health Outcomes (51.2% women; mean age 44.8 years), we recorded the incidence of colorectal cancer and genotyped SNP rs12566888 located in intron 1 of the PEAR1 gene. In 929 participants, we also measured the methylation at 16 CpG sites in the PEAR1 promoter. In multivariable-adjusted analyses, we contrasted the risk of colorectal cancer in minor-allele (T) carriers vs. major allele (GG) homozygotes. We applied partial least square discriminant analysis (PLS-DA) to identify methylation sites associated with colorectal cancer. Results Over a median follow-up of 18.1 years, 49 patients developed colorectal cancer. While accounting for clustering within families and adjusting for sex, age, body mass index, the total-to-HDL cholesterol ratio, serum creatinine, plasma glucose, smoking and drinking, use of antiplatelet and nonsteroidal anti-inflammatory drug, the hazard ratio contrasting minor allele carriers vs. major allele homozygotes was 2.17 (95% confidence interval, 1.18–3.99; P=0.013). Bootstrapped analyses, from which we randomly excluded from two to nine cancer cases, provided confirmatory results. PLS-DA identified two methylation sites in the PEAR1 promoter associated with higher colorectal cancer risk and two with lower risk. In-silico analysis suggested that methylation of the PEAR1 promoter at these four sites affects binding of the transcription factors p53, PAX5, and E2F-1, thereby modulating gene expression. Potential pathways Conclusions Our findings suggest that genetic and epigenetic variation in PEAR1 modulates the risk of colorectal cancer in white Flemish. Acknowledgement/Funding The European Union, the European Research Council, the European Research Area Net for Cardiovascular Diseases, and the Research Foundation Flanders.

Clinical characteristics and prognosis of heart failure with mid-range ejection fraction: insights from a multi-centre registry study in China

BackgroundHeart failure (HF) with mid-range ejection fraction (EF) (HFmrEF) has attracted increasing attention in recent years. However, the understanding of HFmrEF remains limited, especially among Asian patients. Therefore, analysis of a Chinese HF registry was undertaken to explore the clinical characteristics and prognosis of HFmrEF.MethodsA total of 755 HF patients from a multi-centre registry were classified into three groups based on EF measured by echocardiogram at recruitment: HF with reduced EF (HFrEF) (n = 211), HFmrEF (n = 201), and HF with preserved EF (HFpEF) (n = 343). Clinical data were carefully collected and analyzed at baseline. The primary endpoint was all-cause mortality and cardiovascular mortality while the secondary endpoints included hospitalization due to HF and major adverse cardiac events (MACE) during 1-year follow-up. Cox regression and Logistic regression were performed to identify the association between the three EF strata and 1-year outcomes.ResultsThe prevalence of HFmrEF was 26.6% in the observed HF patients. Most of the clinical characteristics of HFmrEF were intermediate between HFrEF and HFpEF. But a significantly higher ratio of prior myocardial infarction (p = 0.002), ischemic heart disease etiology (p = 0.004), antiplatelet drug use (p = 0.009), angioplasty or stent implantation (p = 0.003) were observed in patients with HFmrEF patients than those with HFpEF and HFrEF. Multivariate analysis showed that the HFmrEF group presented a better prognosis than HFrEF in all-cause mortality [p = 0.022, HR (95%CI): 0.473(0.215–0.887)], cardiovascular mortality [p = 0.005, HR (95%CI): 0.270(0.108–0.672)] and MACE [p = 0.034, OR (95%CI): 0.450(0.215–0.941)] at 1 year. However, no significant differences in 1-year outcomes were observed between HFmrEF and HFpEF.ConclusionHFmrEF is a distinctive subgroup of HF. The strikingly prevalence of ischemic history among patients with HFmrEF might indicate a key to profound understanding of HFmrEF. Patients in HFmrEF group presented better 1-year outcomes than HFrEF group. The long-term prognosis and optimal medications for HFmrEF require further investigations.

Correlation Between Cerebral Microbleeds and Vulnerable Plaque in Patients with Severe Carotid Artery Stenosis; Comparative Magnetic Resonance Imaging Study

Goal: There are an increasing idea that the inflammation contributes to vascular diseases in various organs. The pathogenesis of both cerebral small vessel disease such as cerebral microbleeds and carotid plaque may be associated with chronic inflammation. This study was aimed to evaluate the correlation between microbleeds and carotid plaque characteristics. Materials and Methods: This study enrolled 85 patients who underwent surgical/endovascular treatments for carotid artery stenosis between January 2009 and July 2016. Their clinical data were precisely analyzed. T2*-weighted magnetic resonance (MR) imaging was performed to detect the cerebral microbleeds. The carotid plaque with high signal intensity on T1-weighted MR imaging was categorized into vulnerable plaque. Findings: The microbleeds was detected in 17 of 85 (20%). The prevalence of vulnerable carotid plaque and previous symptomatic lacunar infarction was significantly greater in the patients with microbleeds than in those without (P = .001 and P = .03, respectively). Multiple logistic regression analysis showed that the vulnerable plaque was significantly associated with the presence of microbleeds when adjusted for age, alcohol intake, antiplatelet drug use, the presence of previous symptomatic lacunar infarction, and coronary artery disease (P = .009, OR = 5.38, 95% CI = 1.51-21.0). Conclusions: These findings suggest the correlation between microbleeds and vulnerable plaque in patients with severe (>70%) carotid artery stenosis. Systemic, chronic inflammation may play a key role in both small and large arteries’ disease of the brain. The knowledge may be valuable to fully understand the entity of cerebrovascular diseases as one of systemic, chronic inflammation.

Monocyte and macrophage subtypes as paired cell biomarkers for coronary artery disease.

What is the central question of this study? Are circulating monocyte markers correlated with their derived macrophage polarization patterns and coronary artery disease severity? What is the main finding and its importance? There was an inverse relationship between circulating CD16+ monocytes (high) and M2 macrophages (low) that marked coronary disease severity, and the differences in polarization of macrophages were seen despite a week of cell culture ex vivo. This study highlights the importance, and potential prognostic implications, of circulating monocyte and descendant macrophage phenotypes in coronary artery disease. Monocytes and macrophages are central to atherosclerosis, but how they combine to mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients' monocyte subtypes paired with their derived macrophage profiles were correlated with extent of CAD. Peripheral blood was collected from 40 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for the monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7days and measured for the polarization markers CD86 and CD206. At baseline, patients with a greater CAD burden were older, with higher rates of statin, β-blocker and antiplatelet drug use, whereas other characteristics were similar across the spectrum of coronary disease. CD16+ (both intermediate and non-classical) monocytes were elevated in patients with single vessel and multivessel disease compared with those without significant CAD (P<0.05), whereas regulatory M2 macrophages (CD206+ ) were decreased in patients with single vessel and multivessel disease (P<0.001). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. On multivariable linear regression, CAD severity was associated, along with age and traditional cardiovascular risk factors, with CD16+ monocytes (directly) and M2 macrophages (inversely). Circulating monocytes may influence downstream polarization of lesional macrophages, and these measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.

Interaction between serum endotoxemia and proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with atrial fibrillation: A post-hoc analysis from the ATHERO-AF cohort

Background and aimsLipopolysaccharides (LPS) is emerging as a novel risk factor for cardiovascular events (CVEs). Furthermore, in vitro evidence suggested that LPS may elicit proprotein convertase subtilisin/kexin 9 (PCSK9) expression, but their relationship in vivo has not been investigated. MethodsWe conducted a post-hoc analysis of a prospective, single centre cohort study of 907 patients with non-valvular atrial fibrillation (AF). At baseline, PCSK9, LPS and NADPH oxidase (sNox2-dp) were measured. PCSK9 and LPS were correlated with the incidence of CVEs. ResultsMedian PCSK9 and LPS were 1200 [900–1970] and 49.9 [15.0–108.2] pg/ml, respectively. LPS and PCSK9 were significantly correlated (rS 0.378, p < 0.001). Logistic regression analysis showed that LPS was associated with PCSK9 above the median (odds ratio [OR] 1.727 95% confidence interval [CI] 1.147–2.600 p = 0.009). Other factors associated with PCSK9 above the median were sNox2-dp (OR 1.759 C.I. 95% 1.167–2.650, p = 0.007), use of antiplatelet drugs (OR 0.437 95%CI 0.219–0.871 p = 0.017) and high adherence to Mediterranean diet (OR 0.737 95%CI 0.643–0.845 p = 0.001). Olive oil (OR 0.376 95%CI 0.185–0.763, p = 0.001) and wine (OR 0.460 95%CI 0.289–0.733 p = 0.007) were negatively associated with PCSK9.Patients with concomitant high PCSK9 and LPS (LPS ≥88 pg/ml and PCSK9 ≥1570 pg/ml) had an increased risk of CVEs compared to those with low levels (LPS <24.3 pg/ml and PCSK9 <1000 pg/ml, Log-Rank test, p = 0.022). ConclusionsThis study demonstrated, for the first time in vivo, that circulating levels of PCSK9 and LPS are associated with a mechanism possibly involving NADPH oxidase activation. Patients with concomitant increase of PCSK9 and LPS showed a higher risk of CVEs.

Condition of microcirculatory and hemostasis systems in rats after moderate hypothermia

Hypothermia produces a generalized impact on an organism, with involvement of all organs and systems into the response. It was shown that hypothermia promotes multi-organ dysfunction syndrome, which makes it important to study the influence of hypothermia on condition of hemostasis and microcirculatory systems.&#x0D; Aim. To study the condition of the hemostasis system and the microcirculatory bed in different periods of moderate hypothermia in rats.&#x0D; Materials and Methods. The current study was performed on 50 male Wistar rats. Condition of microcirculatory blood stream in all animals was assessed with laser Doppler flowmetry. Condition of hemostasis system was studied according to routine protocols and an integrated method of examination – thromboelastography. Statistical analysis was performed using Statistica 6.0 software package (StatSoft, USA) with calculation of Mann-Whitney nonparametric test.&#x0D; Results. Analysis of the experimental data showed that moderate hypothermia produced a pronounced modulating influence on the microcirculatory system. Vasodilatation occurred immediately after reaching the stage of hypothermia, suggesting the beginning of decompensation in the experimental animals. The highest risk for hemodynamic pathologies was observed 5 days after cessation of cooling and was characterized by a massive reduction in the vascular tone, intensification of hemodynamics against the background appearance of thrombinemia markers in the blood stream and pronounced inhibition of fibrinolysis. Enhanced hemodynamics of the nutritional vascular bed with the underlying progressive prothrombotic condition is a potent risk factor for thrombosis and multiple organ dysfunction syndrome. Vasospasm that developed 2 weeks after recovery of the body temperature, indicated a profound modulation of vasculature and preservation of high-level sympathetic input, as well as increasing rigidity of blood vessel walls. Rising fibrinogen concentrations confirm a progressive inflammatory reaction.&#x0D; Conclusion. A moderate degree of hypothermia produces a pronounced modulating effect on the microcirculation. The established regularities make it possible to form a clear understanding of the course and development of the pathological reaction in the body of victims and to give recommendations on the use of pharmacological medicine for preventive therapy. Thus, a period has been established when thrombotic readiness is maximal, and use of anticoagulant and antiplatelet drugs is required, together with drugs that improve rheological properties of blood.

Primary thrombophilia XV: antithrombotic treatment of sticky platelet syndrome worldwide

Background: Sticky platelet syndrome (SPS) is a common but under-recognized cause of thrombosis. Treatment with antiplatelet drugs results in a low re-thrombosis rate. The aim of this study is to analyze the treatment of persons with SPS in different parts of the world. Methods: Data from 43 publications describing 1,494 patients with SPS worldwide were analyzed. Data concerning treatment was available in 16 of these papers, and involving 332 patients. Results: Three hundred thirty two patients were treated with antiplatelet drugs; 303 were given solely aspirin and 29 received combinations with aspirin (heparin or coumadin), whereas two persons did not receive aspirin. The re-thrombosis rate for patients given antiplatelet drugs was 5/332 (1.5%) and only 3 patients died. Conclusions: Most patients with SPS are treated with antiplatelet drugs worldwide, the re-thrombosis rate is very low. Physicians worldwide are aware of the fact that the best treatment for persons with the SPS is the use of antiplatelet drugs.

Treatment Strategy for Progressive Cervical Internal Carotid Artery Stenosis Under Restriction of the Use of Antiplatelet Drugs

Acute ischemic stroke caused by cervical internal carotid artery stenosis (ICS) with altered consciousness and progressive paralysis leads to a poor neurologic prognosis. When such a patient is brought to the hospital in the hyperacute phase, intravenous tissue plasminogen activator is first administered. However, when an indwelling carotid artery stent is required after administration, physicians often hesitate to use antithrombotic drugs. In this report, we propose performing staged angioplasty (SAP) for such cases. Four patients were retrospectively investigated. In all 4 patients, we immediately performed only percutaneous transluminal angioplasty (PTA) without antiplatelet drugs. If both cerebral perfusion on angiography and neurologic findings improved, no additional treatment was provided; otherwise, emergency carotid artery stenting (eCAS) was performed. In PTA-successful cases, eCAS or carotid endarterectomy (CEA) was performed with single or dual antiplatelet drugs at a later date. The success rate of PTA was 50% (2 of 4), and the overall treatment success rate was 100% (4 of 4). Three patients had favorable outcomes (modified Rankin Scale [mRS] score 0-2), but unfortunately, 1 patient had severe disability (mRS score >3) on discharge. The PTA-successful patients had no perioperative complications. On the other hand, 1 of the 2 patients who underwent eCAS experienced embolic complications, including distal embolization. In this investigation, both eCAS and SAP could be performed safety. However, performing SAP first without antiplatelet drugs to avoid hemorrhagic complications and cerebral hyperperfusion syndrome appears to have considerable validity.

Association between specific plasma ceramides and high-sensitivity C-reactive protein levels in postmenopausal women with type 2 diabetes

AimEmerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, scarce information is currently available on the association between distinct plasma ceramides (that have been associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group of individuals at high risk of developing CVD and other chronic inflammation-related conditions. MethodsWe measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] in 92 postmenopausal women with T2DM attending the diabetes outpatient service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay. ResultsPlasma hs-CRP levels were positively associated with all measured ceramides in univariable linear regression analyses. However, only plasma Cer(d18:1/16:0) (standard β coefficient: 0.27, P=0.015), Cer(d18:1/22:0) (standard β coefficient: 0.25, P=0.032) and Cer(d18:1/24:1) (standard β coefficient: 0.30, P=0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs. ConclusionIn postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors.

Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis

BackgroundHigh serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient’s prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage.MethodsThis cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis.ResultsOf the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43–4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50–10.4; P = 0.005) had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07–2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23–1.59; P < 0.001).ConclusionsAlthough the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient’s calcium level.

French Guidelines for the Management of Ambulatory Endovascular Procedures for Lower Extremity Peripheral Artery Disease

Ambulatory hospitalization for endovascular repair of lower extremity peripheral arterial disease (PAD) could be a real opportunity to respond to the burden of PAD, to reduce costs, and to improve patients' empowerment. The French Society of Vascular and Endovascular Surgery (SCVE) established guidelines to facilitate the development of ambulatory hospitalization in France. In 2017, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and MEDLINE database to conduct a systematic review of available literature. A total of 448 relevant articles were found. Twelve articles, all published after the year 2000, were included and reviewed by two independent investigators. The SCVE mandated a scientific committee to collectively establish these guidelines. Eligibility for ambulatory management shall be based on the assessment of the triad: (1) patient, (2) procedure, and (3) structure. Comprehensive information and a detailed procedural pathway should be provided for the patient. No age limit is recommended. American Society of Anesthesiologists I, II, and III stable patients are eligible for ambulatory intervention. Specific comorbidities such as severe obesity, sleep apnea, and/or chronic kidney failure should be assessed preoperatively. Critical limb ischemia and complex lesions have not been considered as exclusion criteria. Antiplatelet drug use (aspirin and/or clopidogrel) has not been considered as a contraindication. Femoral ultrasound-guided puncture is recommended. Manual compression or closure devices have been recommended for 7F sheath or less. A minimum of 4 hours of monitoring after percutaneous femoral access is required before discharge. The SCVE guidelines aim to frame the practice of ambulatory endovascular procedures for lower extremity peripheral artery disease and to give vascular interventionalists help in their routine practice.

Use of oral anticoagulant drugs is associated with carotid intraplaque hemorrhage in atherosclerosis patients: a meta-analysis.

Patients with carotid atherosclerosis, especially the elderly population, take antithrombotic medicine regularly. However, no previous meta-analysis has focused on one of the possible side effects of such drugs, namely intraplaque hemorrhage (IPH). To determine whether antiplatelet drugs or anticoagulants are associated with an increased risk of carotid IPH. We searched Pubmed, Embase, Ovid MEDLINE, Cochrane Library for relevant studies that were published in English, from January 1st, 1989 to January 1st, 2019. We pooled the odds ratio (OR) with 95% confidence interval (CI) from individual studies and conducted quality assessment, heterogeneity, publication bias analysis and sensitivity analysis. A total of four cross-sectional studies, involving 2714 participants with carotid atherosclerotic plaques was included into this meta-analysis. We found a significant association between the use of anticoagulants and higher risk of carotid IPH (OR 1.95; 95% CI 1.16-3.30, P = 0.92; I2 = 0). No significant association was found between the use of antiplatelet drugs and increased risk of carotid IPH (OR 1.34; 95% CI 0.68-2.61, P = 0.03; I2 = 65%). Our meta-analysis reveals that it is the use of oral anticoagulants rather than antiplatelet drugs that may be associated with an increased risk of carotid IPH in atherosclerosis patients.

Inhibition of platelet aggregation (Update 2019)

Acute thrombotic complications as akey feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in diabetic patients. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in diabetic patients according to current scientific evidence.

Praktyczne zastosowanie wystandaryzowanego ekstraktu z pomidorów – stan wiedzy na rok 2019

Inhibiting the ability of thrombocytes to aggregate is one of the basic directions of pharmacotherapy of the cardiovascular diseases. The use of classical antiplatelet drugs, however, is associated with the risk of bleeding complications. Recent studies have shown that the benefits of using acetylsalicylic acid outweigh the risks only in the case of a confirmed cardiovascular disease. In many other situations – in patients with diabetes, hypertension, obesity, with high cardiovascular risk – safe inhibition of platelet activity would also be very valuable. This possibility is potentially created by standardized extract from tomato seeds. This article summarizes current knowledge about the properties of STE and its applicability in practice.

Pros and cons of antithrombotic therapy in end-stage kidney disease: a 2019 update.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Evaluation of the anticoagulant effect of vitamin K antagonists in patients with non-valvular atrial fibrilation

Background/Aim. Despite the introduction of new oral anticoagulants (dabigatran, rivoroxaban, apixaban), vitamin K antagonists (VKA), such as warfarin and acenocoumarol are still the most widely used oral anticoagulants for the treatment of nonvalvular atrial fibrillation (NVAF). The time in therapeutic range (TTR) represents a measure of the quality of the anticoagulant effect of these drugs, and it is considered that the lower value of TTR is associated with the adverse effects of therapy. The aim of this study was to evaluate of the effectiveness of VKA therapy in patients with NVAF and to identify factors affecting the anticoagulation efficacy. Methods. A retrospective study was conducted on a population of 725 outpatients with NVAF, treated with VKA and followed in the Blood Transfusion Institute of Nis, Serbia, from January to December 2017. Laboratory control of the INR was done from capillary blood of patients on Thrombotrack Solo (Axis Shield, Norway) and Thrombostat (Behnk Elektronik, Germany). Targeted therapeutic INR was between 2.0 and 3.0. For each patient all available INR values were evaluated to calculate the individual TTR according to the Rosendaal method. Results. The study included a total of 725 patients with NVAF which had 6,105 INR measurements, what was 8.13 ? 2.47 INR measurements per patient. The mean value of TTR and was 60.15 ? 17.52%, but 49.72% of patients had TTR less than 60%. Patients were at high risk of thrombosis in 6.15% of time (INR &lt; 1.5) and high risk of bleeding in 2.2% of time (INR &gt; 4.5). The most significant independent factors affecting the quality of VKA therapy were gender, arterial hypertension, diabetes mellitus and the use of amiodarone and antiplatelet drugs (aspirin, clopidogrel). Conclusion. The TTR is undoubtedly useful indicator of the VKA treatment effectiveness. The most important predictors of poorer efficacy of VKA therapy are: arterial hypertension, diabetes mellitus, patients' gender and the use of amiodarone and antiplatelet drugs (aspirin, clopidogrel). To improve the quality of VKA therapy, education of patients and better collaboration with them, as well as a successful teamwork of clinicians are also imperative.

Modified bedside twist drill craniostomy for evacuation of chronic subdural haematoma.

IntroductionStandard craniotomy (SC) and burr hole craniostomy (BHC) are regarded as the standard approaches to chronic subdural haematoma (CSDH). Bedside twist drill craniostomy (TDC), performed at the patient’s bedside, was introduced as an alternative to the standard methods. However, clinical and radiological features of patients treated with TDC and BHC/SC have not been compared.AimTo demonstrate the specific features of CSDH that affect the surgeons’ preferences when selecting patients for TDC.Material and methodsA retrospective analysis of 32 patients treated due to CSDH in the year 2017 at a single institution was performed. Baseline radiological characteristics, clinical status at admission, complication rate and clinical outcomes were compared between BHC/SC and TDC.ResultsOf the 32 patients, 5 (15.6%) were treated using TDC and 27 (84.4%) by SC or BHC. The duration of the TDC procedure was significantly shorter than the time of standard therapies (p < 0.01). There were no differences between TDC and BHC/SC in terms of baseline clinical characteristics, including age, gender, head trauma history, diabetes, hypertension, antiplatelet drug use, clinical manifestation and the Glasgow Coma Scale score (all p > 0.05). Patients treated with TDC had a significantly thicker haematoma (TDC vs. BHC/SC: mean 25.3 mm vs. 14.6 mm) (p < 0.01) and demonstrated a smaller midline shift (TDC vs. BHC/SC: mean 0.5 mm vs. 4.0 mm) (p = 0.01) compared to those treated with BHC/SC.ConclusionsTwist drill craniostomy is a more effective method for CSDH evacuation compared to SC and BHC. This procedure is considered as the first line treatment for patients with a thicker and non-septated haematoma, and with a smaller midline shift.

Abstract TP514: The Effect of Statin Adherence on Cardiovascular Outcomes After Ischemic Stroke in Statin Benefit Group: A Nested Case-Control Study

Backgrounds: Irrespective of the indication for statin, statin adherence after ischemic stroke was associated with better clinical outcome. We studied the association between statin adherence and recurrent cardiovascular (CV) events among the patients with acute ischemic stroke and statin benefit. Methods: Using Comprehensive Registry Collaboration for Stroke in Korea (CRCS-K), patients with acute ischemic stroke were identified. Statin benefit was defined using the secondary prevention guidelines of American Stroke Association in 2014. The data for statin prescription after discharge were obtained from National Health Insurance Services (NHIS) claim data by matching with CRCS-K. Statin adherence was measured by the medication possession ratio (MPR), which was dichotomized, setting a threshold of MPR (&lt;80%) to identify patients who were nonadherent. A nested case-control design was used to evaluate the occurrence of recurrent stroke, myocardial infarction, and all-cause mortality for 1 year after discharge. Each case was matched to 4 controls by age, sex, initial stroke severity and registry entry time. Adjusted conditional logistic regression models were used to estimate the odds ratio (OR) of CV events. Results: Among 11,768 patients in NHIS-CRCS-K matching database, 5,504 patients were the statin benefit group and prescribed with statin on discharge. Overall MPR for 1 year after discharge was 73.1%. Overall CV events for 1 year were 569, which was more prevalent in low adherence group. (MPR &lt;80%, 18.0% vs. ≥80%, 6.5%, p&lt;0.0001) In nested case-control data set, lower adherence to statin was associated with a higher risk of CV events compared with higher adherence (adjusted OR 1.496 [1.174-1.904]) after adjusting hypertension, diabetes mellitus, atrial fibrillation, history of stroke, history of antiplatelet drug use and discharge modified Rankin Scale score. Statin discontinuation was associated with higher risk compared with adequate statin prescription. (adjusted OR 2.075[1.622-2.655]) Conclusion: Adequate statin adherence in the patients with acute ischemic stroke and statin benefit was significantly associated with recurrent CV events.

The Risk of Symptomatic Intracranial Hemorrhage after Thrombolysis for Acute Stroke: Current Concepts and Perspectives.

Background:Thrombolysis is the standard of treatment for acute ischemic stroke, with a time window of up to 4½ h from stroke onset. Despite the long experience with the use of recombinant tissue plasminogen activator and the adherence to protocols symptomatic intracranial hemorrhage (SICH) may occur in around 6% of cases, with high-mortality rate and poor-functional outcomes. Many patients are excluded from thrombolysis on the basis of an evaluation of known risk factors, but there are other less known factors involved.Objective:The purpose of this work is to analyze the less known risk factors for SICH after thrombolysis. A search of articles related with this field has been undertaken in PubMed with the keywords (brain hemorrhage, thrombolysis, and acute ischemic stroke). Some risk factors for SICH have emerged such as previous microbleeds on brain magnetic resonance imaging, leukoaraiosis, and previous antiplatelet drug use or statin use. Serum matrix metalloproteinases have emerged as a promising biomarker for better selection of patients, but further research is needed.Conclusions:In addition to the already known risk factors considered in the standard protocols, an individualized evaluation of risks is needed to minimize the risk of brain hemorrhage after thrombolysis for ischemic stroke.

Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use.

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y12 inhibitors. Cangrelor is an intravenous P2Y12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.