Thrombosis

New Oral Anticoagulants in the Treatment of Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring

Kelly M. Rudd and Elizabeth (Lisa) M. Phillips — Wed, 10 Apr 2013 15:41:08 +0000

Anticoagulation therapy is mandatory in patients with pulmonary embolism to prevent significant morbidity and mortality. The mainstay of therapy has been vitamin-K antagonist therapy bridged with parenteral anticoagulants. The recent approval of new oral anticoagulants (NOACs: apixaban, dabigatran, and rivaroxaban) has generated significant interest in their role in managing venous thromboembolism, especially pulmonary embolism due to their improved pharmacokinetic and pharmacodynamic profiles, predictable anticoagulant response, and lack of required efficacy monitoring. This paper addresses the available literature, on-going clinical trials, highlights critical points, and discusses potential advantages and disadvantages of the new oral anticoagulants in patients with pulmonary embolism.

Prevention and Treatment of Venous Thromboembolism with New Oral Anticoagulants: A Practical Update for Clinicians

Nay Min Tun and Thein Hlaing Oo — Thu, 21 Feb 2013 14:51:43 +0000

Traditional anticoagulants, such as warfarin and enoxaparin, have several limitations, including parenteral administration, need for laboratory monitoring, and ongoing dose adjustment, which may limit optimal patient care. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks, and thereby improve patient care. Several of these agents have been approved for use in the prevention and treatment of venous and/or systemic thromboembolism. The objective of this paper is to provide an overview of the available clinical trial data for these new oral anticoagulants in the prevention and treatment of venous thromboembolism and a practical update for clinicians.

The Efficacy and Safety of Rivaroxaban for Venous Thromboembolism Prophylaxis after Total Hip and Total Knee Arthroplasty

Robert D. Russell, William R. Hotchkiss, Justin R. Knight, and Michael H. Huo — Thu, 21 Feb 2013 11:57:17 +0000

Venous thromboembolism (VTE) is a common complication after total hip and total knee arthroplasty. Currently used methods of VTE prophylaxis after these procedures have important limitations, including parenteral administration, and unpredictable plasma levels requiring frequent monitoring and dose adjustment leading to decreased patient compliance with recommended guidelines. New oral anticoagulants have been demonstrated in clinical trials to be equally efficacious to enoxaparin and allow for fixed dosing without the need for monitoring. Rivaroxaban is one of the new oral anticoagulants and is a direct factor Xa inhibitor that has demonstrated superior efficacy to that of enoxaparin. However, the data also suggest that rivaroxaban has an increased risk of bleeding compared to enoxaparin. This paper reviews the available data on the efficacy and safety of rivaroxaban for VTE prophylaxis after total hip and total knee arthroplasty.

Towards Personalized Medicine Based on Platelet Function Testing for Stent Thrombosis Patients

Tue, 25 Dec 2012 14:22:34 +0000

Stent thrombosis (ST) is a severe and feared complication of coronary stenting. Patients who have suffered from ST are usually treated according to the “one-size-fits-all” dosing regimen of aspirin and clopidogrel. Many ST patients show high on-treatment platelet reactivity (HPR) despite this antiplatelet therapy (APT). It has been shown that HPR is a risk factor for major adverse cardiac events. Therefore, ST patients with HPR are at a high risk for recurrent atherothrombotic events. New insights into the variable response to clopidogrel and the advent of stronger P2Y12 inhibitors prasugrel and ticagrelor have changed the attention from a fixed APT treatment strategy towards “personalized APT strategies.” Strategies can be based on platelet function testing, which gives insight into the overall response of a patient to APT. At our outpatient ST clinic, we practice personalized APT based on platelet function testing to guide the cardiologist to a presumed optimal antiplatelet treatment of ST patients. Beside results of platelet function testing, comedication, clinical characteristics, and genetics have to be considered to decide on personalized APT. Ongoing studies have yet to reveal the optimal personalized APT strategy for cardiologists to prevent their patients from atherothrombotic and bleeding events.

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement

Wed, 21 Nov 2012 10:12:03 +0000

Several randomized and observational studies have reported steady increase in cumulative incidence of late and very late ST (LST/VLST) following first-generation drug-eluting stents (DES: sirolimus-(SES) and paclitaxel-(PES)) up to 5 years. Pathologic studies have identified uncovered struts as the primary substrate responsible for LST/VLST following DES, where delayed arterial healing is associated with stent struts penetrating into the necrotic core, long/overlapping stents, and bifurcation stenting especially in flow divider region. Grade V stent fracture also induces LST/VLST and restenosis. Hypersensitivity reaction is exclusive to SES as an etiology of LST/VLST, whereas malapposition secondary to excessive fibrin deposition is associated with PES. Uncovered struts can be identified in SES and PES with duration of implant beyond 12 months, particularly in stents placed for “off-label” indications. Neoatherosclerosis is another important contributing factor for VLST in DES and bare metal stents (BMS); however, DES shows rapid and more frequent development of neoatherosclerosis than BMS. Future pathologic studies should address the long-term safety of newer generation DES including zotarolimus- and everolimus-eluting stents in terms of the improvement in reendothelialization, decreased inflammation and fibrin deposition as well as a lower incidence of stent fracture-related adverse events, and reduced neoatherosclerosis, which likely contribute to the decreased risk of LST/VLST and better patient outcomes.

Anti-Phospholipid Antibodies in Patients Undergoing Total Joint Replacement Surgery

Wed, 31 Oct 2012 10:05:56 +0000

Background. Patients undergoing joint replacement remain at increased risk for venous thromboembolism (VTE) compared to other types of surgery, regardless of thromboprophylactic regimen. The pathophysiologic processes rendering this group of patients at risk for VTE are multifactorial. Procedure-specific and patient-specific exposures play a role in the postoperative development of VTE, including the development of anti-phospholipid antibodies (aPL). Methods. We measured three aPL (anti-cardiolipin, anti- glycoprotein, and lupus anticoagulant) in 123 subjects undergoing total knee or hip arthroplasty to describe the presence of these antibodies preoperatively and to describe the rate of postoperative seroconversion among those people who were negative preoperatively. Postoperative antibodies were measured at day 7, 14, and 21. Results. The prevalence of aPL antibodies in the preoperative period was 44%, positive subjects were more likely to be smokers () and were less likely to have undergone a previous arthroplasty procedure (). Subjects seroconverted in a 21 day postoperative period at a rate of 79%. Conclusions. These pilot data suggest that the prevalence of aPL in this population both preoperatively and postoperatively is higher than previously expected. Further studies are needed to describe aPL in a larger population and to establish their clinical significance in populations undergoing joint replacement surgeries.

Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin

Christian Doutremepuich — Sun, 21 Oct 2012 11:22:16 +0000

The Role of Anticoagulation Clinics in the Era of New Oral Anticoagulants

Sun, 14 Oct 2012 16:32:45 +0000

Anticoagulation Clinics (ACs) are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs), but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs) have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.

Thromboembolic Prophylaxis in Total Joint Arthroplasty

David Knesek, Todd C. Peterson, and David C. Markel — Sun, 16 Sep 2012 08:56:00 +0000

Approximately 775,000 hip and knee arthroplasties are performed yearly in the United States, with a dramatic increase expected. Patients having hip and knee arthroplasties are at high risk of developing a venous thromboembolism. The American College of Chest Physicians (ACCP) and the American Academy of Orthopedic Surgeons (AAOS) have updated guidelines, which outline new prophylactic strategies. Factor Xa inhibitor rivaroxaban has a new recommendation by ACCP and is gradually being adopted by the joint arthroplasty community as an effective oral agent. Other more well-known agents including warfarin, low-molecular-weight heparin, aspirin, and fondaparinux continue to be options for prophylaxis. While the goal of prophylaxis continues to be the prevention of venous thromboemboli and pulmonary emboli, it is important to consider the increased bleeding risk associated with their use. The most recent ACCP and AAOS guidelines give clinicians a greater autonomy in choosing a prophylactic agent with greater emphasis placed on dialogue between the surgeon and patient as to the choice of prophylaxis.

Management of Venous Thromboembolism in Patients with Advanced Gastrointestinal Cancers: What Is the Role of Novel Oral Anticoagulants?

Ludmila Katherine Martin and Tanios Bekaii-Saab — Tue, 11 Sep 2012 15:50:29 +0000

Venous thromboembolism (VTE) is a frequent complication of gastrointestinal cancers that increases morbidity and may impact mortality. Low-molecular-weight heparins (LMWHs) and vitamin K antagonists (VKAs) are standard anticoagulation options for the ambulatory gastrointestinal cancer patient with VTE, but both of these agents are challenging to use for various reasons. Novel oral anticoagulants (NOAs) are new, orally available anticoagulants designed to be easier to administer with more reliable pharmacokinetics that eliminate the need for frequent monitoring of various laboratory parameters. This paper reviews the existing efficacy and safety data for the use of NOAs dabigatran etexilate, rivaroxaban, and apixaban and discusses the potential role of these agents in the management of gastrointestinal cancer-related VTE.

Stroke Prevention in Atrial Fibrillation: Understanding the New Oral Anticoagulants Dabigatran, Rivaroxaban, and Apixaban

Mon, 10 Sep 2012 15:10:24 +0000

Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)—direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban—do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)—the RE-LY, ROCKET AF, and ARISTOTLE trials—demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.

Reversible Crystallization of Argatroban after Subcutaneous Application in Pigs

Mercedes Lopez and Goetz Nowak — Mon, 03 Sep 2012 08:49:32 +0000

Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin-induced thrombocytopenia. It is usually administered as an intravenous bolus followed by infusion. Nevertheless, its pharmacokinetics after subcutaneous administration is unknown. The aim of this study was to assess the pharmacokinetics of two different formulations of argatroban in pigs after subcutaneous administration. Antithrombotic activity in plasma was determined by ecarin chromogenic assay. To visualize the formation of crystals, argatroban was administered to rats into the subcutaneous tissue exposed after removing the skin, and the injection site was photographed at different times. After subcutaneous administration of a sorbitol/ethanol formulation of argatroban in pigs was observed a slow absorption phase was followed by long-lasting levels of this inhibitor. 𝐶max and AUC(0−24) showed dose-dependent increases, while elimination half-life and 𝑡max value did not change significantly with dose. In contrast, saline-dissolved argatroban showed a faster absorption phase followed by a shorter elimination half-life. Argatroban dissolved in sorbitol/ethanol leads to long-lasting plasma levels due to the formation and permanent dissolution of a crystalline depot at the injection place. This represents a simple way to deliver argatroban continuously over an extended period which can be beneficial for prophylaxis or treatment of chronic coagulations disorders.

Actual Situation of Thromboembolic Prophylaxis in Obesity Surgery: Data of Quality Assurance in Bariatric Surgery in Germany

Mon, 09 Jul 2012 18:18:37 +0000

Background. Evidence-based data on optimal approach for prophylaxis of deep venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is discussed. Using antithrombotic prophylaxis weight adjusted the risk of VTE and its complications have to be balanced with the increased bleeding risk. Methods. Since 2005 the current situation for bariatric surgery has been examined by quality assurance study in Germany. As a prospective multicenter observational study, data on the type, regimen, and time course of VTE prophylaxis were documented. The incidences of clinically diagnosed VTE or PE were derived during the in-hospital course and follow up. Results. Overall, 11,835 bariatric procedures were performed between January 2005 and December 2010. Most performed procedures were 2730 gastric banding (GB); 4901 Roux-en-Y-gastric bypass (RYGBP) procedures, and 3026 sleeve gastrectomies (SG). Study collective includes 72.5% (mean BMI 48.1 kg/m2) female and 27.5% (mean BMI 50.5 kg/m2) male patients. Incidence of VTE was 0.06% and of PE 0.08%. Conclusion. VTE prophylaxis regimen depends on BMI and the type of procedure. Despite the low incidence of VTE and PE there is a lack of evidence. Therefore, prospective randomized studies are necessary to determine the optimal VTE prophylaxis for bariatric surgical patients.

Factor V-Leiden Mutation: A Common Risk Factor for Venous Thrombosis among Lebanese Patients

Raghid Kreidy — Tue, 12 Jun 2012 11:06:39 +0000

Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous thrombosis. Material and Methods. From January 2003 to January 2011, 283 consecutive Lebanese patients, diagnosed with deep venous thrombosis (DVT) by duplex scan, were retrospectively reviewed. FVL mutation was tested among patients with conditions highly suggestive of hypercoagulation states (65 patients). Results. FVL mutation was detected among 56.9% of patients, 68.6% of patients younger than 50 years, and 43.4% of patients older than 50 years (𝑃=0.041). FVL mutation was commonly reported in young adults, in patients with pregnancy, estrogen drugs, recurrent DVT, and resistance to anticoagulation. Conclusion. The high rate of FVL mutation observed among Lebanese patients with venous thrombosis is related to the high prevalence of this mutation in the Lebanese population. Thrombophilia screening should be tailored to accommodate a population's risk factor. In countries with high prevalence of FVL, this mutation should be screened among patients younger than 50 years and patients with situations highly suggestive of hypercoagulation states.

Pathological Perspective of Drug-Eluting Stent Thrombosis

Katsumi Inoue — Mon, 14 May 2012 13:34:11 +0000

Although very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation remains a major concern, the precise mechanisms have not been clarified. An association between late acquired incomplete stent apposition (ISA) and VLST of DES has been suggested by several intravascular ultrasound studies demonstrating very high prevalence of ISA in the setting of VLST. To clarify the pathological mechanisms of VLST, we investigated vascular responses of coronary arteries of VLST cases after DES implantation.

Factor V Leiden and Inflammation

Silvia Perez-Pujol, Omer Aras, and Gines Escolar — Mon, 14 May 2012 08:36:35 +0000

Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation.

Everolimus-Eluting versus Paclitaxel-Eluting Stents in Percutaneous Coronary Intervention: Meta-Analysis of Randomized Trials

Ashraf Alazzoni, Ayman Al-Saleh, and Sanjit S. Jolly — Wed, 09 May 2012 10:40:48 +0000

Background. Individual randomized trials have suggested that everolimus-eluting stents may have improved clinical outcomes compared to paclitaxel-eluting stents, but individual trials are underpowered to examine outcomes such as mortality and very late stent thrombosis. Methods. Medline, Cochrane, and conference proceedings were searched for randomized trials comparing everolimus versus paclitaxel-eluting stents for percutaneous coronary intervention. Results. 6792 patients were included from 4 randomized controlled trials. Stent thrombosis was reduced with everolimus stents versus paclitaxel stents (0.7% versus 2.3%; OR: 0.32; CI: 0.20–0.51; 𝑃<0.00001). The reductions in stent thrombosis were observed in (i) early stent thrombosis (within 30 days) (0.2% versus 0.9%; OR: 0.24; 𝑃=0.0005), (ii) late (day 31–365) (0.2% versus 0.6%; OR: 0.32; 𝑃=0.01), and (iii) very late stent thrombosis (>365 days) (0.2% versus 0.8%; OR: 0.34; 𝑃=0.009). The rates of cardiovascular mortality were 1.2% in everolimus group and 1.6% in paclitaxel group (OR: 0.85; 𝑃=0.43). Patients receiving everolimus-eluting stents had significantly lower myocardial infarction events and target vessel revascularization as compared to paclitaxel-eluting stents. Interpretation. Everolimus compared to paclitaxel-eluting stents reduced the incidence of early, late, and very late stent thrombosis as well as target vessel revascularization.

Dabigatran for Stroke Prevention in Nonvalvular Atrial Fibrillation: Answers to Challenging “Real-World” Questions

Mon, 07 May 2012 15:01:37 +0000

Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.

Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

Karl Mischke, Christian Knackstedt, and Nikolaus Marx — Mon, 23 Apr 2012 09:43:32 +0000

Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation.

Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients

Wed, 11 Apr 2012 09:22:53 +0000

Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases) and 206 healthy multiparous women (controls) in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs) markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population.

Experimental Validation of Methods for Prophylaxis against Deep Venous Thrombosis: A Review and Proposal

Paul S. Agutter, P. Colm Malone, and Ian A. Silver — Tue, 10 Apr 2012 12:47:56 +0000

The experimental procedure by which the valve cusp hypoxia (VCH) hypothesis of the etiology of deep venous thrombosis (DVT) was confirmed lends itself to testing of methods of prophylaxis. Similar animal experiments could end the present exclusive reliance on statistical analysis of data from large patient cohorts to evaluate prophylactic regimes. The reduction of need for such (usually retrospective) analyses could enable rationally-based clinical trials of prophylactic methods to be conducted more rapidly, and the success of such trials would lead to decreased incidences of DVT-related mortality and morbidity. This paper reviews the VCH hypothesis (“VCH thesis”, following its corroboration) and its implications for understanding DVT and its sequelae, and outlines the experimental protocol for testing prophylactic methods. The advantages and limitations of the protocol are briefly discussed.

Cerebral Vein Thrombosis Misdiagnosed and Mismanaged

P. K. Sasidharan — Thu, 05 Apr 2012 15:55:32 +0000

Cerebral venous thrombosis (CVT) should be considered in the differential diagnosis of all unexplained CNS disorders of sudden onset. Etiological factors are often subclinical forms of several common thrombophilic states occurring together, rather than the typical inherited and rare causes. Diagnosis is missed because of the heterogeneity in clinical presentation and etiological factors. In several patients with the so called idiopathic CVT nutritional deficiencies and lifestyle issues are more important factors in pathogenesis, rather than single rarer causes. High index of suspicion is the key to diagnosis. Clinical skill has to be fine tuned to diagnose the problem and to identify all the etiological factors. Radiology is essential for diagnosis but relying on radiology alone will lead to missing several cases and even erroneous diagnosis. It is inappropriate to proceed prematurely to laboratory investigations, forgetting proper clinical evaluation by studying diet, lifestyle, and environment of the patients. Success in managing lies in identifying all the contributory causes and correcting all of them giving excellent outcome almost always. Clinical observations based on case series and sharing of such information alone are the means to arrive at a consensus in diagnosis and management.

Evaluation of RANKL/OPG Serum Concentration Ratio as a New Biomarker for Coronary Artery Calcification: A Pilot Study

Wed, 28 Mar 2012 14:21:53 +0000

Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG) protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-𝜅B ligand (RANKL) and preventing it from binding to its receptor, receptor activator of nuclear factor-𝜅B. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD). Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC) in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (𝑃=0.01). Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease.

Stent Thrombosis: Incidence, Predictors and New Technologies

Gill Louise Buchanan, Sandeep Basavarajaiah, and Alaide Chieffo — Sun, 11 Mar 2012 15:39:31 +0000

Some concerns have been raised regarding the risk of late and very late stent thrombosis (ST) following drug-eluting stent implantation. Despite remaining an uncommon complication of percutaneous coronary intervention, when ST occurs, it can be catastrophic to the individual, commonly presenting as acute ST elevation myocardial infarction or sudden cardiac death. The incidence and predictors of ST have been reported in the literature and the role of dual antiplatelet therapies in the avoidance of such a complication remains vital. Ongoing studies are assessing the role of these therapies including platelet reactivity testing, genetic testing and optimum duration of therapy. In addition, newer polymer-free and bioabsorbable stents are under investigation in the quest to potentially minimise the risk of ST.

The Avantgarde Carbostent in Patients Scheduled for Undelayable Noncardiac Surgery

Carlo Briguori, Gabriella Visconti, Francesca De Micco, and Amelia Focaccio — Sun, 19 Feb 2012 11:38:31 +0000

Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the AvantgardeTM Carbostent (CID, Italy) in patients undergoing PCI before undelayable non-cardiac surgery. The Multiplate analyzer point-of-care was used to assess residual platelet reactivity. One major cardiac events (MACE, defined as death, myocardial infarction, and stent thrombosis and major bleeding) were assessed. Results. 42 consecutive patients were analyzed. Total stent length ≥25 mm was observed in 16 (37%) patients. Multivessel stenting was performed in 11 (31.5%) patients. Clopidogrel was interrupted 5 days before surgery in 35 patients, whereas it was stopped the day of the surgery in 7 patients. Surgery was performed after 27±9 (7–42) days from PCI. MACE occurred in one patient (2.4%; 95% confidence interval: 0.01–13%), who had fatal acute myocardial infarction 3 days after abdominal aortic aneurysm surgery and 12 days after stent implantation. No case of major bleeding in the postoperative phase was observed. Conclusions. The present pilot study suggests that, although at least 10–14 days of dual antiplatelet therapy remain mandatory, the AvantgardeTM stent seems to have a role in patients requiring undelayable surgery.

Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations

Gundu H. R. Rao and Jawad Fareed — Tue, 07 Feb 2012 12:29:49 +0000

Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies.

The Role of Dermcidin Isoform 2: A Two-Faceted Atherosclerotic Risk Factor for Coronary Artery Disease and the Effect of Acetyl Salicylic Acid on It

Rajeshwary Ghosh, Uttam K. Maji, Rabindra Bhattacharya, and Asru K. Sinha — Mon, 06 Feb 2012 15:39:38 +0000

Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 μM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.

Evaluating the Role of Compression Stockings in Preventing Post thrombotic Syndrome: A Review of the Literature

Abir O. Kanaan, Jayne E. Lepage, Shabdis Djazayeri, and Jennifer L. Donovan — Tue, 17 Jan 2012 08:27:30 +0000

Background. Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT). Up to 50% of patients with DVT will develop the disease within two years following the diagnosis of acute DVT. Various risk factors for developing PTS have been identified and different modalities have been used to prevent its development. Compression stockings have been studied for the prevention of PTS in patients diagnosed with proximal DVT. Methods. MEDLINE and EMBASE databases were searched to identify relevant original articles. Results. Several trials including two metaanalyses have examined the role of compression stockings for the prevention of PTS. Although most trials showed significant reduction in the development of PTS with the use of compression stockings, limitations in study design prevent the generalizability of the data. Two studies supported an individualized tailored duration especially in patients at low risk for developing the syndrome. A randomized double-blind placebo-controlled trial involving 800 patients is currently ongoing and may confirm the results of older studies. Conclusions. Clinical trials support the use of compression stockings in patients diagnosed with proximal DVT for the prevention of PTS.

Paradoxical Effect of Aspirin

Sun, 15 Jan 2012 13:25:58 +0000

Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, basedon its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This paper provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke. In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, being hemorrhagic stroke. Regarding these clinical facts, normal, COX 1 −/−, and COX 2 −/− mice were treated with a wide range of doses of aspirin and studied by induced hemorrhagic time. The results outlined three major conclusions: high doses of aspirin induce hemorrhage, while low doses of aspirin do not. In the absence of COX 1, ultra low doses of aspirin produce an antihemorrhagic effect not observed with intermediate doses. The absence of COX 2 induced a hemorrhagic effect that needs further research, probably originated in compensatory phenomena.

Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms

Bianca Rocca and Giovanna Petrucci — Wed, 11 Jan 2012 16:09:36 +0000

The main pharmacological aspects of pharmacodynamics (PD) and pharmacokinetics (PK) of aspirin as antiplatelet agent were unravelled between the late sixties and the eighties, and low-dose aspirin given once daily has been shown to be a mainstay in the current treatment and prevention of cardiovascular disorders. Nevertheless, several PD and PK aspects of aspirin in selected clinical conditions have recently emerged and deserve future clinical attention. In 1994, the term “aspirin resistance” was used for the first time, but, until now, no consensus exists on definition, standardized assay, underlying mechanisms, clinical impact, and possible efficacy of alternative therapeutic interventions. At variance with an undefined aspirin-resistant status, in the last 5 years, the concept of variability in response to aspirin due to specific pathophysiological mechanisms and based on PK and/or PD of the drug has emerged. This growing evidence highlights the existence and possible clinical relevance of an interindividual variability of pharmacological aspirin response and calls for new, large studies to test new low-dose aspirin-based regimens which may ameliorate platelet acetylation, reduce variability in drug responsiveness, and improve clinical efficacy on selected populations.