Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography

Objectives:

To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients.

Methods:

This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA) after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as ≤15% platelet inhibition or >213 P2Y12 reaction units (PRU).

Results:

Three hundred and four patients were included in the study. The mean age was 60.3 ± 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%), 600 mg (27%), and 75 mg (16%). All patients used aspirin (81 mg in 94%). Approximately 66% (200/304) showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005) and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002) remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014) remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated.

Conclusion:

Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography.Platelets play a critical role in the pathogenesis of atherothrombotic diseases such as coronary artery disease (CAD). The rupture of atherosclerotic plaques initiates a complex process of platelet adhesion, activation, and aggregation.1 Recently, clopidogrel and aspirin were the cornerstones of oral antiplatelet therapy for preventing ischemic events of atherothrombotic disease such as myocardial infarction and stroke.2,3 Clopidogrel was shown to be even more effective than aspirin in preventing such events of atherothrombotic disease.4 Clopidogrel is a prodrug and the active metabolite is generated by the cytochrome P450 system.5 The active metabolite acts by inhibiting platelet aggregation in response to adenosine diphosphate (ADP) through binding and blocking the platelet P2Y12 receptors.5 Variability in individual responsiveness to the antiplatelet effects of clopidogrel may lead to the occurrence of thromboembolic events despite regular antiplatelet therapy.6,7 This may be clinically translated into poor procedural and long-term morbidity and mortality outcomes.8,9 The prevalence of clopidogrel non-response (resistance) is highly variable in different studies and populations. A review10 estimated the non-response rate to range from 4-30%. This variability is partly caused by the lack of standard definition and the different assessment methods of clopidogrel non-response.11,12 A number of studies examined the patients characteristics associated with clopidogrel non-response but failed to identify any, probably due to small sample sizes and the presence of multiple confounding factors.13-15 Although, approximately 84% of Saudi patients admitted with acute coronary syndrome are treated with clopidogrel,16 there is lack of estimates of clopidogrel non-response and the associated risk factors in this population. The objective of the current study was to estimate the prevalence of clopidogrel non-response and to identify its risk factors among Saudi patients undergoing coronary angiography at a specialized cardiac center in Kingdom of Saudi Arabia (KSA).     

Microbiologic spectrum and visual outcome of posttraumatic endophthalmitis

PURPOSE: To identify the microbiologic spectrum and visual outcome of infectious endophthalmitis after open globe injuries. METHODS: We reviewed the medical records of all patients with culture-positive endophthalmitis after open globe injuries who were treated at King Khaled Eye Specialist Hospital and King Abdulaziz University Hospital (Riyadh, Saudi Arabia) between January 1, 1993, and December 31, 2003. RESULTS: Sixty-seven patients were identified. There were 55 males and 12 females (mean age +/- SD, 23.3 +/- 18.3 years; range, 2-65 years). The mean follow-up +/- SD was 18.8 +/- 23.9 months (range, 1-120 months). Twenty-nine eyes (43%) had intraocular foreign bodies (IOFBs). A single species was isolated from 59 eyes, and multiple organisms were isolated from 8 eyes (total number of infecting organisms, 78). The most common isolates were coagulase-negative staphylococci and Streptococcus species (26.9% of isolates each). Gram-negative organisms and fungi comprised 12.8% and 3.8% of isolates, respectively. Staphylococcus epidermidis comprised 37.1% of isolates in the group with IOFBs and 16.3% of isolates in the group without IOFBs (P = 0.0358). Streptococcus species comprised 41.8% of isolates in the group without IOFBs and 8.6% of isolates in the group with IOFBs (P = 0.0024). Final visual acuity was 20/200 or better in 30 eyes (47.6%). Visual acuity of 20/200 or better at presentation (P = 0.0474) and time from injury to presentation to our institutes of <1 day (P = 0.0348) were significantly associated with better visual acuity outcome. Final visual acuity of 20/200 or better was achieved in 61.9% of patients infected with nonvirulent organisms compared with 40.5% of patients infected with virulent organisms. CONCLUSIONS: The most common organisms identified were coagulase-negative staphylococci and Streptococcus species. Clinical features associated with better visual acuity outcomes included better presenting visual acuity, early presentation to our institutes, and isolation of a nonvirulent organism. Posttraumatic endophthalmitis is associated with a poor visual prognosis.     

Synthesis and anti‐inflammatory activity of diversified heterocyclic systems

In continuation with our research program on the development of novel bioactive molecules, we report herein the design and synthesis of a series of diversified heterocycles ( 4 – 22 ). The synthesized compounds were evaluated for their anti‐inflammatory activity. The chemical structures of the newly synthesized compounds have been confirmed by NMR, FTIR, and microanalysis.     

Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-Mycobacterium tuberculosis activity

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generated in situ from indenoquinoxaline and l-tryptophan and reacts with various substituted β-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C–C and three C–N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for their in vitro activity against Mycobacterium tuberculosis H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 μg mL⁻¹) to ethambutol against Mycobacterium tuberculosis H37Rv.

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel spiropyrrolidine tethered indole hybrids in excellent yields employing a one-pot multicomponent 1,3-dipolar cycloaddition strategy.     

Recent advances in syntheses,properties and applications of TiO2 nanostructures

TiO₂ is a compound of great importance due to its remarkable catalytic and distinctive semiconducting properties. It is also a chemically stable, non-toxic and biocompatible material. Nano TiO₂ is strong oxidizing agent with a large surface area and, hence, high photo-catalytic activities. With low production cost and a high dielectric constant, it is an inexpensive material. It can be prepared by diverse procedures such as solution and gas phase procedures. Nowadays, TiO₂ is being used frequently for photo degradation of organic molecules and water splitting for hydrogen generation. Most important applications include purification, disinfection of waste water, self-cleaning coatings for buildings in urban areas and the production of the green currency of energy (hydrogen) by splitting water. The review describes the advances in the syntheses, properties and applications of TiO₂ nano structures. Besides, efforts are also made to discuss the working mechanism and future challenges and perspectives.

TiO₂ is a compound of great importance due to its remarkable catalytic and distinctive semiconducting properties.     

Molecular docking,pharmacophore based virtual screening and molecular dynamics studies towards the identification of potential leads for the management of H. pylori

The enzyme pantothenate synthetase panC is one of the potential new antimicrobial drug targets, but it is poorly characterized in H. pylori. H. pylori infection can cause gastric cancer and the management of H. pylori infection is crucial in various gastric ulcers and gastric cancer. The current study describes the use of innovative drug discovery and design approaches like comparative metabolic pathway analysis (Metacyc), exploration of database of essential genes (DEG), homology modelling, pharmacophore based virtual screening, ADMET studies and molecular dynamics simulations in identifying potential lead compounds for the H. pylori specific panC. The top ranked virtual hits STOCK1N-60270, STOCK1N-63040, STOCK1N-44424 and STOCK1N-63231 can act as templates for synthesis of new H. pylori inhibitors and they hold a promise in the management of gastric cancers caused by H. pylori.

Computational approaches such as pharmacophore modeling, virtual screening and MD simulations were explored to find the potential hits as H. pylori specific panC inhibitors for the management of gastric ulcers and gastric cancers.