- Effect of obesity and serum leptin level on clopidogrel resistance. [Journal Article]
- TKTurk Kardiyol Dern Ars 2016; 44(7):548-553
- CONCLUSIONS: Clopidogrel resistance is more common in obese and hyperleptinemic patients. Dosage should be individualized in these populations.
- Obesity, leptin, and thrombosis: Focus on clopidogrel resistance. [Editorial]
- TKTurk Kardiyol Dern Ars 2016; 44(7):543-544
- Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel. [Journal Article]
- FPFront Pharmacol 2016; 7:366
- Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inac...
Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 μg⋅h/L, p < 0.05) and CAM (10119 vs. 2634 μg⋅h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L⋅h(-1)⋅kg(-1), p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL⋅h(-1)⋅kg(-1)) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver.
- Oral antiplatelet therapy and platelet inhibition: An experience from a tertiary care center. [Journal Article]
- IHIndian Heart J 2016 Sep - Oct; 68(5):624-631
- CONCLUSIONS: Use of ticagrelor as dual therapy along with aspirin in patients with coronary artery disease (CAD) and undergoing PCI was associated with a significantly higher mean percentage platelet inhibition, higher sensitivity, and lower resistance as compared with the usage of clopidogrel or prasugrel.
- Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model. [Journal Article]
- IJInt J Pharm 2016 Nov 20; 513(1-2):332-346
- The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA...
The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.
- Evaluating Blood Loss and the Effect of Antiplatelet Treatment in Foot and Ankle Amputations. [Journal Article]
- JFJ Foot Ankle Surg 2016 Sep 7
- The interrelationship between diabetes mellitus and cardiovascular disease is well-documented, and, secondary to the latter, is the use of antiplatelet therapy. Although diabetes and the associated v...
The interrelationship between diabetes mellitus and cardiovascular disease is well-documented, and, secondary to the latter, is the use of antiplatelet therapy. Although diabetes and the associated vascular manifestations are driving forces behind lower extremity amputations, few data are available on the risks of perioperative antiplatelet therapy with foot and ankle amputations. The goal of the present study was to address the surgical effect of continuing or discontinuing antiplatelet therapy before foot and/or ankle amputation. The following data were retrospectively collected: blood loss, pre- and postoperative hematocrit and hemoglobin, operative time, amputation type, age, diabetic status, antiplatelet treatment, and number of transfusions during the perioperative period. Perioperative antiplatelet therapy was defined as exposure to aspirin or clopidogrel within 3 days before surgery. To compare the outcomes between groups, the following factors were analyzed using bivariate analyses and then multivariate regression models: (1) the need for transfusions, (2) high blood loss (>20 mL), (3) volume of blood loss, and (4) operative time. The noninferiority of continued antiplatelet use was assessed in terms of operative time and blood loss, using a noninferiority margin of 10 minutes or 10 mL, respectively. Antiplatelet therapy was not a statistically significant risk factor for any of the studied outcomes on multivariate analysis. Equivalence testing revealed that continuing antiplatelet therapy is not inferior to discontinuing perioperative therapy in terms of blood loss and operative time. Multivariate analysis of the data suggested that antiplatelet therapy has no statistically significant impact on blood loss, transfusion rate, or operative time.
- Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention. [Journal Article]
- PPharmacogenomics 2016 Oct 21
- CONCLUSIONS: Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.
- Landscape of warfarin and clopidogrel pharmacogenetic variants in Qatari population from whole exome datasets. [Journal Article]
- PPharmacogenomics 2016 Oct 21
- CONCLUSIONS: This is one of the first and most comprehensive pharmacogenetic maps of variants associated with warfarin and clopidogrel for an Arab population, which can help tailor the drug dosage to the population.
- Impact of different antithrombotics on the microcirculation and viability of perforator-based ischaemic skin flaps in a small animal model. [Journal Article]
- SRSci Rep 2016 Oct 21; 6:35833
- The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical is...
The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical ischaemia model was used to evaluate the effects of different perioperatively administered pharmaceutical agents on tissue ischaemia and to assess the potential additional haemorheological or vasodilative effects of antithrombotics on flap microcirculation. Combined laser Doppler flowmetry and remission spectroscopy revealed an increase in certain microcirculation parameters in most groups in comparison with saline controls, and these changes correlated with flap survival. Clopidogrel and hirudin significantly improved the amount of viable flap tissue in comparison with controls, while unfractioned heparin had a negative effect on flap survival. Low molecular weight heparin, aspirin, pentoxifylline, and hydroxyethyl starch had no impact on the amount of viable flap tissue. A higher complication rate was observed in all experimental groups, but only clopidogrel had a negative impact on the flap viability. Our results add to the body of evidence supporting the conclusion that perioperative antithrombotic treatment improves flap survival. Clopidogrel and hirudin are effective pharmacological agents that significantly increased the viability of perforator-based skin flaps in rats, but at a higher risk of postoperative bleeding.
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- Aspirin plus tirofiban inhibit the thrombosis induced by Russell's viper venom. [Journal Article]
- TJThromb J 2016; 14(Suppl 1):38
- CONCLUSIONS: The aspirin + tirofiban group had a better outcome with respect to prevention of tissue ischemia and gangrene. This indicates that the activation and aggregation of platelets is the major cause of thrombosis induced by RVV.