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Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.

What is known and objective: The aim of this study was to clarify the low‐density lipoprotein (LDL)‐C level achievement rate and detect factors affecting the failed LDL‐C achievement rate in patients treated with statins and anti‐platelet agents using a large insurance claim database and health check‐up data. Methods: Access to a large health insurance claims database, and health check‐up data were obtained from Japan Medical Data Center (JMDC) Co. Ltd., Tokyo. The database was searched to identify employed working‐age male patients who had started treatment with statin and anti‐platelet drugs for the secondary prevention of cardiovascular events. These patients were enrolled in the retrospective cohort study, which included screening at 3 months and observation for 3 years. LDL‐C levels were obtained from the annual health check‐up data. The achievement rate for LDL‐C < 100 was assessed for three consecutive years. Adherence was assessed using the proportion of days covered (PDC) for the statin, which was calculated from prescription data over a 3‐year period. Results and discussion: Overall, 294 patients (male/female, 294/0; age, 47.8 ± 6.0 years; body mass index, 24.8 ± 4.2 kg/m2; hypertension, 76.2%; and diabetes mellitus, 20.4%) were included. The LDL‐C achievement rate for three consecutive years after starting treatment with statin and aspirin was 49.7%, 51.4% and 45.9%, respectively. Factors affecting failed LDL‐C on adjusted odds were lower adherence to PDC [0.96 (0.94‐0.99), P < 0.001, 1% increase] and higher baseline LDL‐C [1.01 (1.00‐1.02), P = 0.037, 1 mg/dL increase]. What is new and conclusion: Our results suggest that in the working‐age male population need to improve statin adherence, especially those with higher baseline LDL‐C levels. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of aspirin therapy discontinuation on intraoperative blood loss in spinal surgery. We searched Medline and Google Scholar 1946 to January 2017 inclusive for case-control studies, cohort studies, and controlled trials reporting intraoperative blood loss during spinal surgery in patients on pre-operative aspirin. Other outcome measures reported in the eligible studies were collected as secondary outcomes. Two reviewers independently screened and extracted data from each study. Five retrospective cohort and two case-control studies were eligible for inclusion. Of the 1173 patients identified, 587 patients were never on aspirin (Ax), 416 patients had aspirin discontinued before surgery (Ad), ranging from 3 to 10 days, and 170 patients had aspirin continued until surgery (Ac). Six out of seven studies reported no statistically significant difference in intraoperative blood loss irrespective of aspirin discontinuation. Meta-analysis was not possible due to high risk of bias. Of the secondary outcome measures, operative time and postoperative complications were most commonly reported. One of six studies evaluating operative time reported a significantly longer operative time in the Ad group compared with the Ac group. The overall risk of postoperative haematoma in Ax, Ad, and Ac groups is 0.2% (n/N = 1/587), 0.2% (n/N = 1/416), and 1.2% (n/N = 2/170), respectively. No study reported a statistically significant difference in postoperative complications. There is no strong evidence demonstrating a difference in intraoperative blood loss, operation time, and postoperative complications, irrespective of aspirin discontinuation. This is, however, based on a limited number of studies and higher-quality research is required to answer this question with a higher degree of confidence. [ABSTRACT FROM AUTHOR]

Abstract BackgroundIt is sometimes difficult to choose anti‐thrombotic agents for secondary prevention in stroke patients at high bleeding risk. Recently, Eicosapentaenoic Acid (EPA) was reported to reduce the recurrence of stroke in hypercholesterolemic patients without increasing hemorrhagic risk. In this study, we investigated the features of recurrent stroke patients during EPA medication as secondary stroke prevention. MethodsFollowing the approval of the ethical committee, stroke patients in the outpatient clinic were consecutively screened and patients who continuously take EPA were enrolled in this study (n = 71, average age 69.7 yo). Blood sample data was adopted from the latest visit or the admission at the stroke recurrence. According to the previous stroke history, all patients were classified into the hemorrhagic stroke (HS) group (n = 10) and the ischemic stroke, including asymptomatic infarction, (IS) group (n = 61). ResultAny stroke recurrence was not observed in the HS group. Whereas, ischemic stroke recurrence was observed in 6 patients in the IS group, although there was no hemorrhagic stroke recurrence. Recurrent stroke patients showed the higher serum level of cholesterol or the renal dysfunction. The stroke subtype of patients were 2 embolic strokes, 3 atherothrombotic infarctions (two were compromised with renal failure and one had insufficient amount of EPA) and one lacunar infarction (who showed high triglyceride level). ConclusionHemorrhagic stroke was not occurred in our observation of EPA prescribed patients. The clinical features of recurrent stroke patients were the existing complications of dyslipidemia and renal dysfunction.

The modalities to treat bleeding polyps include electrocautery snare polypectomy, adrenaline injection, clipping, argon plasma coagulation and surgery. We hereby describe an endoscopic banding ligation method for the management of bleeding gastric polyp in a patient receiving antiplatelet therapy. A 66-year-old man presented with a five month-history of intermittent tarry stool passage, nausea and fatigue. He had a past history of peripheral arterial occlusive disease and non-insulin dependent diabetes mellitus with end stage renal disease, and regularly took antiplatelet agent (ticlopidine 100 mg thrice daily) for cardiovascular prophylaxis. On examination, the patient was grossly pale, ill in appearance, with a pulse of 110/min and blood pressure of 108/76 mmHg. Laboratory examination revealed hemoglobin of 7.8 g/dl. Endoscopic examination revealed a bleeding sessile polyp over the posterior wall of the antrum. Endoscopic banding ligation was carried out by a pneumoactivated esophageal variceal ligation device set. Bleeding stopped immediately following the procedure, and the patient recovered uneventfully. It is suggested that endoscopic banding ligation is a safe and effective technique for the treatment of bleeding gastrointestinal polyps in patients receiving antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Surgeons commonly need to treat patients receiving anticoagulant and anti-platelet therapy. This requires risk assessment and management to balance minimization of bleeding complications and avoidance of further ischaemic or thrombotic events. This review considers the evidence available to guide management of patients on anti-platelet and anticoagulant therapy, including some of the new classes of anti-platelets and anticoagulants which clinicians may be less familiar with. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Low-dose aspirin for the prevention of cardiovascular disease is recommended to be discontinued at least 7 days before spinal surgery. Purpose: To determine the effect of stopping low-dose aspirin at least 7 days before surgery on the level of the perioperative blood loss or complications related to hemorrhage. Study design: Retrospective case study. Patient sample: Patients who underwent spinal fusion surgery for degenerative lumbar disease. Outcome measure: Clinical outcome was measured by the Oswestry Disability Index. Methods: The aspirin group included 38 patients who had taken 100 mg aspirin for an average of 40.3 months. They stopped aspirin for at least 7 days before surgery (mean, 9.0 days). The control group included 38 patients who had not taken aspirin. Both groups were matched in terms of age, gender, number of fused segments, and surgical procedures. The diagnosis in all patients was degenerative spinal disease. Results: The mean age in the aspirin and control groups was 68.5 and 69.1 years, respectively. The mean number of levels fused was 2.0 segments in both groups. During surgery, the estimated blood loss was 855.3 cc in the aspirin group and 840.8 cc in the control group with no significant difference (p=.84). However, there was a significant difference in blood drainage after surgery. The hemovac blood drainage after surgery was 864.4 cc in the aspirin group but only 458.4 cc in the control group (p<.001). Therefore, the transfusion requirement after surgery was significantly greater in the aspirin group than in the control group (p=.03). The rate of complications related to hemorrhage was higher in the aspirin group than in the control group. Conclusions: The intraoperative blood loss during spinal fusion surgery was similar in both groups. However, the blood drainage after surgery was significantly higher in the aspirin group despite stopping aspirin 7 days before surgery. Hence, surgeons should pay careful attention to postoperative blood loss and complications related to hemorrhage in patients who have been taking low-dose aspirin. [Copyright &y& Elsevier]

Abstract: Background: Endoscopic submucosal dissection is a novel technique that is expected to be a curative treatment for early gastric cancers. Anti-coagulants and anti-platelet agents are widely used, especially in elderly patients, to prevent thromboembolic disease. However, the feasibility of endoscopic submucosal dissection for such patients has not been investigated. Aims: To determine the feasibility of endoscopic submucosal dissection for patients using anti-coagulant and anti-platelet agents via retrospective investigation of clinical outcomes. Methods: Of 408 patients with 444 early gastric cancers consecutively treated by endoscopic submucosal dissection from January 2000 to December 2007 in our hospital, 47 patients with 56 early gastric cancers were receiving anti-coagulants or anti-platelet agents. All patients were classified into groups for high and low risk of thromboembolism. In 44 low-risk patients, these agents were stopped for 1 week before and after treatment. Only three high-risk patients underwent intravenous heparin replacement during the cessation period. Results: Comparison with other patients showed no significant differences in complete en-bloc resection (96.4%) or perforation (1.8%). Postoperative bleeding requiring endoscopic treatment occurred for six early gastric cancers (10.7%) in the anti-coagulant and anti-platelet group; this frequency was slightly higher than that observed for other patients (5.2%). The healing of endoscopic submucosal dissection ulcers was not delayed by anti-coagulant and anti-platelet treatment (91% in the scarring stage) when checked at the 8th week after endoscopic submucosal dissection. Conclusion: The clinical outcomes of endoscopic submucosal dissection for early gastric cancers in patients receiving anti-coagulants or anti-platelet agents indicated that endoscopic submucosal dissection for low-risk patients could be a reliable technique with equivalent efficacy and risk in comparison with that for other early gastric cancer patients. [Copyright &y& Elsevier]

Abstract: K-134 ((–)-6-[3-[3-cyclopropyl-3-[(1R, 2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2(1H)-quinolinone) is a novel anti-platelet agent with anti-hyperplastic activities. We found previously that K-134 is a potent phosphodiesterase-3 (PDE3) inhibitor. In the present study, we found other K-134-binding proteins by Drug-Western method. We isolated two clones that can bind directly to K-134, cofilin-2, and CD36 in vitro. Comparison of their amino acid sequences showed similarity over a short stretch [KxxxxVxIxWxxE] in part in the collagen-binding region of CD36. K-134 inhibited binding between CD36 and collagen type-I; however, other PDE3 inhibitors, cilostazol, amrinone, and an inactive derivative of K-134, 4S-OH-K-134, showed little or no effect on binding. It was strongly suggested that the direct binding between K-134 and CD36 is a characteristic effect of K-134, and the homologous stretch may be necessary for binding to K-134. These results also suggested that these interactions are involved in the mechanisms of the anti-platelet and anti-hyperplastic effects of K-134. [Copyright &y& Elsevier]

Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs. [ABSTRACT FROM AUTHOR]

The ADMIRAL (Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up) study is a multicentre, double-blind trial in 300 patients presenting with myocardial infarction. They were randomised to treatment with abciximab or placebo, followed by stenting. Abciximab treatment in diabetic and non-diabetic patients improved outcomes at 30 days and 6 months, with these improvements being related to a higher frequency of normal coronary blood flow at 24 hours and 6 months after intervention. [ABSTRACT FROM PUBLISHER]