Clopidogrel Research Articles

Effects of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after PCI.

To evaluate the effect of individualized antiplatelet therapy based on CYP2C19 genotype and platelet function on the prognosis of patients after percutaneous coronary intervention (PCI) compared with conventional antiplatelet therapy. Patients diagnosed with acute coronary syndromes (ACS) in Shandong Provincial Qianfoshan Hospital from December 2014 to December 2017 were included in this prospective study and randomly divided into conventional (CA) and individualized antiplatelet therapy group (IA) at 1:1 ratio. Patients in the CA group received clopidogrel 75 mg once a day (QD). Group IA was divided into extensive, intermediate, and poor metabolizers according to the results of the CYP2C19 gene test. Three genotypes were given clopidogrel 75 mg QD, 75 mg twice daily (BID) and ticagrelor 90 mg BID respectively. After taking these medicines for a period of time, platelet function was monitored by thromboelastography (TEG) and MAADP values were recorded. MAADP indicates the adenosine diphosphate (ADP) induced platelet function that not inhibited by medicine. High platelet reactivity (HPR) was defined as MAADP > 47mm, indicating a high risk of thrombus, and MAADP ≤ 31 mm indicates a high risk of hemorrhage. For extensive metabolizers (EMs) and intermediate metabolizers (IMs) patients with HPR, the antiplatelet therapy would be changed by the clinician according to the patient's conditions. Major adverse cardiovascular events (MACE) and hemorrhage events were monitored during 1-year follow-up. The patients with MAADP > 47 mm were 89 (28.6%) in the IA group. There were 50 EMs patients with MAADP > 47 mm (33.3%). Of which, there were 2 cases which changed the dosage of clopidogrel to 75 mg BID, 14 cases who changed clopidogrel to ticagrelor. There were 36 IMs patients with MAADP > 47 mm (30.8%). Of which, there were 19 cases who changed clopidogrel to ticagrelor. There was no significant difference in the value of MAADP between EMs and IMs patients. Within 1 year after PCI, the occurrence of MACE in the IA group was significantly lower than that in the CA group (p=0.010). (1) Patients with a CYP2C19 loss-of-function (LOF) gene who take double doses of clopidogrel overcome the decreased efficacy of clopidogrel which partly due to CYP2C19 LOF gene, without increasing the risk of hemorrhage. (2) Individualized antiplatelet therapy based on CYP2C19 genotype and platelet function can significantly reduce the occurrence of MACE (mainly acute non-fatal myocardial infarction) after PCI without increasing the risk of moderate or severe hemorrhage.

One-Step Fabrication of Electrochemical Reduced Graphene Oxide-Carboxyl Functionalized Multiwalled Carbon Nanotubes Film and Its Use as a Platform for Determination of Clopidogrel Bisulfate

In this work, one-step fabrication of electrochemical reduced graphene oxide-carboxyl functionalized multi-walled carbon nanotubes (ErGO-[Formula: see text]MWCNTs) was successfully presented using potentiostatic method (PM). Characteristics of nanocomposite film were studied by using scanning electron microscopic (SEM) and electrochemical experiments. Furthermore, nanocomposite film of ErGO-[Formula: see text]MWCNTs was presented to develop a sensitive voltammetric sensor for detection of clopidogrel bisulphate (CLP). Electrochemical tests showed that nanocomposite film of ErGO-[Formula: see text]MWCNTs modified electrode can effectively increase currents to the oxidation of CLP due to the large accessible surface area as well as its excellent conductivity. Under optimum conditions, response peak currents were linear related to CLP in the range of [Formula: see text] to [Formula: see text] with a lower detection limits of [Formula: see text] ([Formula: see text]). Moreover, the proposed method exhibited an excellent selectivity, stability, reproducibility and was applied successfully for determination of CLP content in tablet dosage form with acceptable recovery values.

Effect of X-Ray Irradiation on Some Analgesics, Anti-Diabetics, PPI’S, Anti-Hypertensives, Heart Failure Drugs in Tablet and Capsule Forms

X-ray is an ionizing-radiation and it has been used in many processes due to the developing technology. For security purposes, X-ray instruments are been using at the entrance of the airports, shopping centers, etc. In this study, potential effects of X-ray were investigated on five different types of drugs: analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), proton pump inhibitors (lansoprazole, pantoprazole sodium sesquihydrate), anti-diabetics (metformin HCl, pioglitazone), heart failure drugs (verapamil HCl, spironolactone) and anti-hypertensives (losartan, clopidogrel hydrogen sulphate) by several different methods.In our previous study these drugs were analyzed by ESR before and after X-ray irradiation (0,24; 1,2; 58 mGy). According to the ESR results, acetylsalicylic acid tablets were affected after 58 mGy irradiation due to coated polymer (HPMC).In conclusion, these drugs were investigated before and after 0,24; 1,2 and 58 mGy X-ray irradiation by UV-spectrophotometry, dissolution test, SEM, FT-IR, DSC/TGA in this article. As a result of this study, X-ray did not cause a significant effect on drugs generally. Only a few significant differences were detected by different studies (for metformin HCl by DSC/TGA, for acetylsalicylic acid by dissolution test, and for acetaminophen and acetylsalicylic acid by UV spectrophotometry were detected significantly difference before and after irradiation).

Preparation and in vitro biorelevant evaluation of clopidogrel bisulfate solid dispersions

Preparation and in vitro biorelevant evaluation of clopidogrel bisulfate solid dispersions

Precision Medicine for Poor Metabolizers of Clopidogrel

Clopidogrel, an inhibitor of the platelet adenosine diphosphate P2Y12 receptor, is a prodrug that needs to be processed into an active metabolite by

Design and Characterization of Bilayered Floating Tablets of Clopidogrel Bisulfate and Aspirin using Natural Gums

Objectives: In present investigation, an attempt was made to develop bilayered floating tablets of clopidogrel bisulfate and aspirin using natural gums as release retarded material. Clopidogrel bisulfate and aspirin are anti-platelet agents. Methodology: Clopidogrel bisulfate is a suitable candidate for formulating as gastro retentive dosage form as it has absorption window in stomach and solubility in the acidic pH. Sodium bicarbonate and citric acid were used to get desired floating properties. The effect of formulation variables on floating properties and drug release were investigated. Results: The tablets so designed were evaluated and found to have acceptable physicochemical properties, floating lag time, floating time and drug release. Among all the bilayered formulations, CBXA with susutained.release layer containing xanthan gum (2 ratio with drug), sodium bicarbonate (15% w/w) and citric acid (1.2% w/w) and immediate release layer containing sodium bicarbonate (10% w/w) and guar gum (4% w/w) has shown optimum results. Sustained release layer has shown dissolution of 99.03±0.42 % in 12 hrs whereas immediate release layer has shown 99.4±0.44 % in 30mins.CBXA has shown optimum floating properties with in vitro floating lag time of 4 min and floating time of >12 hr. In vivo buoyancy study revealed that the floating time of CBXA was greater than 6 hr. The in vitro release data of optimized formulation was treated with mathematical equations and was evident that drug release followed zero order kinetics with case II transport mechanism. Conclusion: Based on the results it can be found that bilayered floating tablets of clopidogrel bisulfate and aspirin containing xanthan gum provides a better approach for sustained release and improved bioavailability. Key words: Clopidogrel bisulfate, Bilayered floating tablets, Susutained. release layer, Immediate release layer and Bioavailability.

Enhancement of Solubility And Dissolution Profile of Clopidogrel By Various Solid Dispersion Formulations

The present research is aimed at enhancing solubility and drug dissolution of clopidogrel (CPG) used as oral antiplatelet agent by employing solid dispersion (SD) technique. Total 40 SDs formulated with drug: polymers (pluronic F127, poloxamer 407, labrafil PG, PEG 6000, gelucire 50/13), in varying ratios (1:0.5, 1:1, 1:2, 1:3, 1:4) of which CPG1 to CPG20 and CPG21 to CPG40 prepared by adopting solvent evaporation method fusion (melt) method respectively. The formulation CPG40 containing pluronic F127 as polymer showed highest solubility of 6.57±0.04 mg/ml) that is 45 folds than pure drug. Similar results reflected in the dissolution studies where CPG40 containing CPG: pluronic F127 in 1:4 ratio showed maximum % drug content, % practical yield and drug dissolution of 99.14% in 60 minutes when compared with other formulations and pure drug (32.76%) obtained by fusion melt method. From FTIR studies the optimized formulation CPG40 showed the compatibility between drug and polymers. XRD and SEM studies showed CPG40 exists in amorphous form that fetched in better drug release from the SD formulation in comparison to pure drug.

Liquid chromatographic and potentiometric methods for deteminations of clopidogrel

Two different techniques are developed for the determination of clopidogrel in pharmaceutical preparations. HPLC method has been developed where chromatographic analysis is performed on Nova-Pak(superscript ®) C18 column (3.9 mm×150 mm, 5 μm) with an ammonium formate buffer adjusted with formic acid to pH 4.0, acetonitrile (40:60, v/v) as mobile phase, and detection at 225 nm. Good linearity (0.9993, r), accuracy (≥99.20%) and precision (≤0.6 RSD) were obtained. Potentiometric measurments are based on tetrakis (p-chlorophenyl) borate-clopidogrel ion-pair as an electroactive material incorporating a plasticized PVC membrane with o-nitrophenyl octyl ether or dioctyl phthalate. The sensor is conditioned for at least two days in 0.1 M drug solution before use. It exhibits fast and stable Nernstian response for clopidogrel over the concentration range of 1.0×10^(-5)~1.0×10^(-2) M and pH range of 1.5-4.0. Results with an average recovery of 100.6% and a mean standard deviation of 0.86% of the nominal were obtained. The sensor shows reasonable selectivity towards clopidogrel hydrogen sulphate in presence of many cations. No significant interferences are caused by drug excipients and diluents.

In Vitro Dissolution Study of Acetylsalicylic Acid and Clopidogrel Bisulfate Solid Dispersions: Validation of the RP-HPLC Method for Simultaneous Analysis

Solid dispersions were prepared via a solvent evaporation method, employing ethanol (96%, v/v) as solvent, with three different polymers as carrier: povidone, copovidone, and poloxamer 407. Previously developed reversed-phase HPLC (RP-HPLC) methods were modified and used for the simultaneous determination of acetylsalicylic acid and clopidogrel bisulfate and after release from solid dispersions. Chromatography was carried out on a C-18 column, with a mobile phase of acetonitrile–methanol–phosphate buffer pH 3.0, UV detection at 240 nm, and a run time of 6 min. The method was validated according to International Conference of Harmonisation guidelines and validation included specificity, accuracy, precision, linearity, robustness, limit of detection (LOD), and limit of quantification (LOQ). The method is specific for determination of acetylsalicylic acid and clopidogrel bisulfate. The linearity was provided in the concentration range 0.0275–0.1375 mg/mL for acetylsalicylic acid and 0.0200–0.1000 mg/mL for clopidogrel bisulfate, with a correlation coefficient (R2 value) of 0.9999 for both active pharmaceutical ingredients (APIs). Accuracy was confirmed by calculated recoveries for acetylsalicylic acid (98.6–101.0%) and clopidogrel bisulfate (100.0–101.6%). The intra-day and the inter-day precision-calculated relative standard deviations are less than 1%, which indicates high precision of the method. The limits of detection and quantification for acetylsalicylic acid were 0.0004 and 0.0012 mg/mL, and for clopidogrel bisulfate 0.0002 mg/mL and 0.0007 mg/mL, respectively. Small variations in chromatographic conditions did not significantly affect qualitative and quantitative system responses, which proved robustness of method. The proposed RP-HPLC method was applied for simultaneous determination of clopidogrel bisulfate and acetylsalicylic acid from solid dispersions.

Anterior wall myocardial infarction in a 16-year-old man caused by coronary artery aneurysm during the outbreak of COVID-19

BackgroundCoronary artery aneurysm (CAA) is a potential cause of infarction. During the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability. Here, we report a case of sudden acute myocardial infarction caused by large CAA during the home isolation.Case presentationDuring the outbreak of coronavirus disease 2019 (COVID-19),a 16-year-old man with no cardiac history was admitted to CCU of Tang du hospital because of severe chest pain for 8 h. The patient reached the hospital its own, his electrocardiogram showed typical features of anterior wall infarction, echocardiography was performed and revealed local anterior wall dysfunction, but left ventricle ejection fraction was normal, initial high-sensitivity troponin level was 7.51 ng/mL (<1.0 ng/mL). The patient received loading dose of aspirin and clopidogrel bisulfate and a total occlusion of the LAD was observed in the emergency coronary angiography (CAG). After repeated aspiration of the thrombus, TIMI blood flow reached level 3. Coronary artery aneurysm was visualized in the last angiography. No stent was implanted. Intravascular ultrasound (IVUS) was performed and the diagnosis of coronary artery aneurysm was further confirmed. The patient was discharged with a better health condition.ConclusionsCoronary artery aneurysm is a potential reason of infarction, CAG and IVUS are valuable tools in diagnosis in such cases, during the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability, and activities at home should be increased in the high-risk patients.

Study on clinical characteristics of Danshen Chuanxiongqin Injection in treatment of cerebral infarction in real world

In this study, the clinical characteristics and drug combination rules of Danshen Chuanxiongqin Injection in the treatment of patients with cerebral infarction were analyzed. The inpatient information of 2 857 patients of cerebral infarction treated with Danshen Chuanxiongqin Injection in HIS database of 20 grade Ⅲ class A hospitals in China was collected, and a model was established by description analysis and Apriori algorithm, in order to explore the clinical characteristics and drug combination rules of Danshen Chuan-xiongqin Injection in the treatment of cerebral infarction. The results showed that among patients of cerebral infarction treated with Danshen Chuanxiongqin Injection, 1 727 patients were older than 65 years old, accounting for 69.61%, and 1 610 were males, accounting for 63.59%. Commonly used drugs included lipid-lowering agents, anticoagulant thrombolytic agents, antiplatelet agents, stimulants of brain metabolism, vasodilators and other Western drugs, as well as traditional Chinese medicines, such as blood-activating agents, heat-clearing agents and expectorant agents. The Western medicine with the highest use frequency in combination with Danshen Chuan-xiongqin Injection was aspirin enteric-coated tablets(1 528 cases, 53.48%). The traditional Chinese medicine with the highest use frequency in combination with Danshen Chuanxiongqin Injection was Xingnaojing Injection, with a total of 378 cases, accounting for 13.23%. Among them, the most commonly used Western drugs combined with Danshen Chuanxiongqin Injection were anticoagulant thrombolytic and antiplatelet drugs, with a usage rate as high as 83.48%. In order to further explore the drug combination rules of Danshen Chuanxiongqin Injection, the association analysis of drug combination in patients of cerebral infarction treated with Danshen Chuanxiongqin Injection was carried out. In clinical combination of two Western drugs, Atorvastatin Calcium Capsules+Cerebral Proteolytic Injection were the most common combination, with a support of 27.10%. In clinical combination with 3 Western drugs, Clopidogrel Bisulfate Tablets+Atorvastatin Calcium Capsules+Cerebral Proteolytic Injection were most commonly used, with a support of 15.90%. The results showed that the patients of cerebral infarction treated with Danshen Chuanxiongqin Injection were mainly elderly males, and often complicated with hypertension, coronary heart disease, diabetes and other basic diseases. The clinical application of Danshen Chuanxiongqin Injection was principally in line with the guidelines. In the treatment of cerebral infarction, it was often combined with Western medicine anticoagulant thrombolysis, antiplatelet drugs, traditional Chinese medicine blood-activating and stasis-dissolving prescription and other drugs with similar pharmacological effects, with an auxiliary therapeutic effect on patients of cerebral infarction complicated with other diseases, and can provide guidance for clinical medication.

STABILITY-INDICATING METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF ROSUVASTATIN CALCIUM AND CLOPIDOGREL BISULFATE IN PHARMACEUTICAL DOSAGE FORM BY REVERSE-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: The present work was focused on the development and validation of reversed-phase high-performance liquid chromatography (RP-HPLC) method which is simple, rapid, precise, accurate, sensitive, economical, and stability-indicating for the quantification of rosuvastatin (RSV) calcium and clopidogrel bisulfate (CLO) in bulk and tablet formulation.&#x0D; Methods: The separation was attained on RP Princeton (C18) column with dimensions (250 mm × 4.6 mm, 5 μ) employing buffer which is a mixture of water (pH 3.0, adjusted with orthophosphoric acid), and methanol in the ratio (20:80) v/v as mobile phase, at flow rate 1.0 ml/min and detection was carried out at wavelength 240 nm. The retention time under the optimized condition of RSV calcium and CLO was found to be 2.844 min and 4.388 min, respectively.&#x0D; Results: The linearity of the method was demonstrated in the concentration range of 6–16 µg/ml and 45–120 µg/ml for RSV calcium and CLO with a correlation coefficient (r2) of 0.9999 and 0.9996, respectively. The percentage relative standard deviation was ˂2% and percentage recovery was found to be 100.12–101.37% and 99.72–101.09% for RSV calcium and CLO, respectively. Assay of marketed tablet formulation was found to be 98.99% and 99.92%, respectively.&#x0D; Conclusion: The developed RP-HPLC method was found to be simple, specific, sensitive, rapid, linear, accurate, precise, and economical and could be used for regular quality control of RSV calcium and CLO in bulk and tablet formulations.

SLRP1 (Soluble Low-Density Lipoprotein Receptor-Related Protein 1): A Novel Biomarker for P2Y12 (P2Y Purinoceptor 12) Receptor Expression in Atherosclerotic Plaques.

Recent studies suggest that the P2Y12 (P2Y purinoceptor 12) receptor of vascular smooth muscle cells in atherosclerotic plaques aggravates atherosclerosis, and P2Y12 receptor inhibitors such as CDL (clopidogrel) may effectively treat atherosclerosis. It is imperative to identify an effective biomarker for reflecting the P2Y12 receptor expression on vascular smooth muscle cells in plaques. Approach and Results: We found that there was a positive correlation between the level of circulating sLRP1 (soluble low-density lipoprotein receptor-related protein 1) and the number of LRP1+ α-SMA+ (α-smooth muscle actin), P2Y12+, or P2Y12+ LRP1+ cells in plaques from apoE-/- mice fed a high-fat diet. Furthermore, activation of the P2Y12 receptor increased the expression and shedding of LRP1 in vascular smooth muscle cells by inhibiting cAMP (3'-5'-cyclic adenosine monophosphate)/PKA (protein kinase A)/SREBP-2 (sterol regulatory element binding transcription factor 2). Conversely, genetic knockdown or pharmacological inhibition of the P2Y12 receptor had the opposite effects. Additionally, CDL decreased the number of lesional LRP1+ α-SMA+ cells and the levels of circulating sLRP1 by activating cAMP/PKA/SREBP-2 in apoE-/- mice fed a high-fat diet. Our study suggests that sLRP1 may be a biomarker that reflects the P2Y12 receptor level in plaques and has the potential to be an indicator for administering P2Y12 receptor inhibitors for patients with atherosclerosis.

ESR INVESTIGATIONS of X-RAY EXPOSED DRUGS

X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres, etc. for security purposes. Therefore, human beings and belongings are frequently exposed to X-ray by transiting these checkpoints at various sites such as airports, shopping centres etc. This study aims is to investigate the X-rays potential effects (arising from security machines) on different groups of medicines which are analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), anti-diabetics (metformin HCl, pioglitazone), PPI’s (lansoprazole, pantoprazole sesquihydrate), anti-hypertensives (losartan, clopidogrel hydrogen sulphate), heart failure medicines (verapamil HCl, spironolactone) used frequently and daily, by using ESR analysis. Coated acetylsalicylic acid tablets showed different intensities of ESR signals after 58 mGy irradiation. It thought to be the result of the coating polymer (Hydroxypropylmethylcellulose (HPMC)). According to the ESR results which were obtained for 0,24-58 mGy irradiated drugs- 1 hour after irradiation (refrigerated during this period) X-ray did not affect those medicines except the acetylsalicylic acid tablets significantly. The meaningful differences were only obtained between the non-irradiated, and 58 mGy irradiated acetylsalicylic acid tablets. Therefore, it can be concluded that X-ray exposed medicines, except coated acetylsalicylic acid tablets (after 58 mGy irradiation), can be used safely for the irradiation levels used in this study (0.24 mGy-0.58 mGy). In addition those data, ESR analyses were followed by other analysis such as FT-IR, DSC/TGA, dissolution, SEM, etc., and they are planned to be published soon.

Freeze-Dried Clopidogrel Loaded Lyotropic Liquid Crystal: Box-Behnken Optimization, In-Vitro and In-Vivo Evaluation.

Clopidogrel (CLP) suffers from extensive first pass metabolism results in a negative impact on its oral systemic bioavailability. Cubosomes are Lyotropic Liquid Crystalline (LLC) nano-systems comprising monoolein, a steric stabilizer and an aqueous system, it considered a promising carrier for different pharmaceutical compounds. Box-Behnken Design (BBD) is an efficient tool for process analysis and optimization skipping forceful treatment combinations. The study was designed to develop freeze-dried clopidogrel loaded LLC (cubosomes) for enhancement of its oral bioavailability. A 33 BBD was adopted, the studied independent factors were glyceryl monooleate (GMO lipid phase), Pluronic F127 (PL F127steric stabilizer) and polyvinyl alcohol powder (stabilizer). Particle Size (PS), Polydispersity Index (PDI) and Zeta Potential (ZP) were set as independent response variables. Seventeen formulae were prepared in accordance with the bottom up approach and in-vitro evaluated regarding PS, PDI and ZP. Statistical analysis and optimization were achieved using design expert software®, then the optimum suggested formula was prepared, in-vitro revaluated, freeze-dried with 3% mannitol (cryoprotectant), solid state characterized and finally packed in hard gelatin capsule for comparative in-vitro release and in-vivo evaluation to Plavix®. Results of statistical analysis of each individual response revealed a quadratic model for PS and PDI where a linear model for ZP. The optimum suggested formula with desirability factor equal 0.990 consisting of (200 mg GMO, 78.15 mg PL F127 and 2% PVA). LC/MS/MS study confirmed significant higher Cmax, AUC0-24h and AUC0-∞ than that of Plavix®. The results confirm the capability of developed carrier to overcome the low oral bioavailability.

Solubility Measurement and Data Correlation of Clopidogrel Hydrogen Sulfate (Form I) in Four Binary Solvents Systems at Temperature from 278.15 to 318.15 K

Experimental solubility data of clopidogrel hydrogen sulfate (form I) in four binary solvents (1-propanol + isopropyl acetate, 2-propanol + isopropyl acetate, 1-butanol + isopropyl acetate, and 2-b...

Clopidogrel response in ischemic stroke patients: Is polymorphism or gender more important? Results of the CRISP study

Clopidogrel (CLP) is a second generation thienopyridine drug commonly used in secondary prevention of ischemic stroke (IS). Its antiplatelet response maybe variable due to genetic and non-genetic factors. Adipokines may affect platelet aggregation through ADP mediated platelet signalling. However, the combined effect of CYP genetic variants and adipokines on antiplatelet response of clopidogrel is unclear. Patients of IS/Transient ischemic attack (TIAs) within 3 months were prospectively screened following clopidogrel treatment. Major exclusions were cardioembolic and non atherosclerotic strokes. Antiplatelet effect of clopidogrel along with adipokine (Leptin and adiponectin) levels and genotyping of CYP, P2Y12 gene were investigated. Rare genetic variants were confirmed by DNA sequencing. 204 patients with ischemic stroke/TIAs were screened and 163 were recruited. 85 (52.1%) patients were poor responders to clopidogrel. Antiplatelet response to clopidogrel was weaker in females [Median 8.0 (IQR: 3.0–14.0)] compared to males [Median 5.0 (IQR: 2.0–10.0)]. In female subgroup analysis, association was found among high leptin levels and PPI (+) usage in poor responders. None of the genetic variants (CYP2C19*2,*3,*4*, CYP2C9*3, CYP2B6 and P2Y12) were found to influence the antiplatelet effects (p > 0.05). On multivariable logistic regression, a poor clopidogrel response was associated with female gender (Adjusted OR 2.55, 95% CI: 1.05–6.18) and PPI usage (Adjusted OR 2.42, 95% CI: 1.09–5.34). Despite a high prevalence of clopidogrel resistance in the North Indian stroke patients, female gender rather than genetic polymorphisms of CYP and P2Y12 genes may influence its antiplatelet effect. Further research may ascertain the role of gender on clopidogrel response.

Ticagrelor-Induced complete heart block: A rare entity

Ticagrelor, a purinergic P2Y12 receptor blocker, is a potent platelet antagonist and an important component in the treatment for acute coronary syndromes identified to have a potential risk to cause bradyarrhythmias. Here, we report the case of a diabetic patient of unstable angina with left bundle branch block who was prescribed ticagrelor post angioplasty. Electrocardiogram (ECG) revealed a complete heart block after about 1 week. Ticagrelor was stopped and replaced by clopidogrel. The patient became asymptomatic and ECG showed baseline rhythm after 1 week of stoppage of ticagrelor.

Should Clopidogrel Be Added to Anticoagulation After TAVI

The POPular TAVI trial (NCT02247128) is a randomized, open-label European trial of oral anticoagulation (OAC) with a vitamin K antagonist (VKA) or

Nucleation kinetics of clopidogrel hydrogen sulfate polymorphs in reactive crystallization: Induction period and interfacial tension measurements

Nucleation kinetics of clopidogrel hydrogen sulfate polymorphs has been investigated in the mixture of 2-butanol and ethyl acetate by reactive crystallization. The effect of supersaturation and temperature on the nucleation rate was researched by measuring the induction period. The results show that the induction period decreases with the increase of supersaturation and temperature. After identifying the form of nuclei, the results disclose the metastable form seems to favor generating at a high supersaturation level. The reasons have been explained from the view of critical nucleation size. The interfacial energy of two polymorphs (20 °C, γslI = 4.49 mJ/m2, γslII = 4.94 mJ/m2; 25 °C, γslI = 5.60 mJ/m2, γslII = 6.27 mJ/m2) was also determined from induction time. The value calculated of Form II at 25 °C was close to the ones obtained from directly methods: by contact angle measurement (6.85 mJ/m2). The effect of different contents of ethyl acetate on the induction period at 20 °C was also explored. The results reveal the addition of a small amount of ethyl acetate can significantly promote nucleating.