Displaying publications 1 - 20 of 114 in total

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  1. Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis
    Lim ST, Thijs V, Murphy SJX, Fernandez-Cadenas I, Montaner J, Offiah C, et al.
    J Neurol, 2020 Oct;267(10):3021-3037.
    PMID: 32518978 DOI: 10.1007/s00415-020-09932-y
    BACKGROUND: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear.

    METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up.

    RESULTS: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01).

    DISCUSSION: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  2. Fulltext Use of antiplatelet drugs and the risk of mortality in patients with COVID-19: a meta-analysis
    Kow CS, Hasan SS
    J Thromb Thrombolysis, 2021 Jul;52(1):124-129.
    PMID: 33813716 DOI: 10.1007/s11239-021-02436-0
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  3. Prasugrel over ticagrelor in non-ST-elevation acute coronary syndromes: is it justified?
    Kow CS, Zaihan AF, Hasan SS
    Eur Heart J, 2021 07 08;42(26):2609-2610.
    PMID: 33205147 DOI: 10.1093/eurheartj/ehaa880
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  4. Inhibitory activities of compounds from the twigs of Garcinia hombroniana Pierre on human low-density lipoprotein (LDL) oxidation and platelet aggregation
    Saputri FC, Jantan I
    Phytother Res, 2012 Dec;26(12):1845-50.
    PMID: 22422639 DOI: 10.1002/ptr.4667
    The methanol extract of the twigs of Garcinia hombroniana, which showed strong LDL antioxidation and antiplatelet aggregation activities, was subjected to column chromatography to obtain 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone, 1,7-dihydroxyxanthone and eight triterpenoids, garcihombronane B, D, E and F, friedelin, glutin-5-en-3β-ol, stigmasterol and lupeol. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit copper-mediated LDL oxidation and arachidonic acid (AA)-, adenosine diphosphate (ADP)-, collagen-induced platelet aggregation in vitro. Among the compounds tested, 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone and 1,7-dihydroxyxanthone showed strong inhibitory activity on LDL oxidation with half-maximal inhibitory concentration (IC(50)) values of 6.6 and 1.7 µM, respectively. 3,5,3',5'-Tetrahydroxy-4-methoxybenzophenone exhibited strong activity on AA-, ADP- and collagen-induced platelet aggregation with IC(50) values of 53.6, 125.7 and 178.6 µM, respectively, while 1,7 dihydroxyxanthone showed significant and selective inhibitory activity against ADP-induced aggregation with IC(50) value of 5.7 µM. Of the triterpenoids tested, garcihombronane B showed moderate activity against LDL oxidation and garcihombronane D and F showed selective inhibition on ADP-induced platelet aggregation.
    Matched MeSH terms: Platelet Aggregation/drug effects*; Platelet Aggregation Inhibitors/pharmacology*
  5. Antiplatelet activity of aporphine and phenanthrenoid alkaloids from Aromadendron elegans Blume
    Jantan I, Raweh SM, Yasin YH, Murad S
    Phytother Res, 2006 Jun;20(6):493-6.
    PMID: 16619347
    Six aporphine and one phenanthrenoid alkaloids isolated from Aromadendron elegans Blume were investigated for their ability to inhibit arachidonic acid (AA), collagen and ADP induced platelet aggregation in human whole blood. The antiplatelet activity of the compounds was measured in vitro by the Chrono Log whole blood aggregometer using an electrical impedance method. Of the compounds tested, (-)-N-acetylnornuciferine, (-)-N-acetylanonaine and 1-(N-acetyl-N-methylamino)ethyl-3,4,6-trimethoxy-7-hydroxyphenanthrene showed strong inhibition on platelet aggregation caused by all three inducers. (-)-N-acetylanonaine was the most effective antiplatelet compound as it inhibited both arachidonic acid, collagen and ADP-induced platelet aggregation with IC(50) values of 66.1, 95.1 and 80.6 microm, respectively.
    Matched MeSH terms: Platelet Aggregation/drug effects*; Platelet Aggregation Inhibitors/isolation & purification*
  6. Fulltext Impact of specific functional groups in flavonoids on the modulation of platelet activation
    Ravishankar D, Salamah M, Akimbaev A, Williams HF, Albadawi DAI, Vaiyapuri R, et al.
    Sci Rep, 2018 Jun 22;8(1):9528.
    PMID: 29934595 DOI: 10.1038/s41598-018-27809-z
    Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
    Matched MeSH terms: Platelet Aggregation/drug effects; Platelet Aggregation Inhibitors/pharmacology*; Platelet Aggregation Inhibitors/chemistry*
  7. Benzophenones and xanthones from Garcinia cantleyana var. cantleyana and their inhibitory activities on human low-density lipoprotein oxidation and platelet aggregation
    Jantan I, Saputri FC
    Phytochemistry, 2012 Aug;80:58-63.
    PMID: 22640928 DOI: 10.1016/j.phytochem.2012.05.003
    Three benzophenones, 2,6,3',5'-tetrahydroxybenzophenone (1), 3,4,5,3',5'-pentahydroxybenzophenone (3) and 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'-enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var. cantleyana. Eight known compounds, 3,4,5,3'-tetrahydroxy benzophenone (2), 1,3,5-trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3β-ol and friedelin were also isolated. The structures of the compounds were elucidated by spectroscopic methods. The compounds were investigated for their ability to inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human whole blood in vitro. Most of the compounds showed strong antioxidant activity with compound 8 showing the highest inhibition with an IC₅₀ value of 0.5 μM, comparable to that of probucol. Among the compounds tested, only compound 4 exhibited strong inhibitory activity against platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5 and 8 showed selective inhibitory activity on platelet aggregation induced by ADP.
    Matched MeSH terms: Platelet Aggregation/drug effects*; Platelet Aggregation Inhibitors/isolation & purification; Platelet Aggregation Inhibitors/pharmacology; Platelet Aggregation Inhibitors/chemistry
  8. Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants
    Jantan I, Rafi IA, Jalil J
    Phytomedicine, 2005 Jan;12(1-2):88-92.
    PMID: 15693713
    Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).
    Matched MeSH terms: Platelet Aggregation/drug effects*; Platelet Aggregation Inhibitors/administration & dosage; Platelet Aggregation Inhibitors/pharmacology*; Platelet Aggregation Inhibitors/therapeutic use
  9. Fulltext Update on the management of peripheral arterial disease (PAD)
    Liew NC, Moissinac K, Lee L, Gee T, Zezeman RB
    Med J Malaysia, 2011 Oct;66(4):386-8; quiz 389.
    PMID: 22299571 MyJurnal
    There has been much progress made in the management of peripheral arterial disease (PAD) in the past two decades. Progress in the understanding of the endothelial-platelet interaction during health and disease state have resulted in better antiplatelet drugs that can prevent platelet aggregation, activation and thrombosis during angioplasty and stenting. Collaborative effort by different international societies has resulted in a consensus guideline that recommends the modality of intervention in certain disease states. Progress in perioperative care has reduced the morbidity and mortality associated with peripheral vascular reconstruction surgery. Nevertheless, the advances in percutaneous peripheral intervention (PPI) have made a paradigm shift in the current management of patients. The procedure is safe and effective and is emerging as the first choice revascularization procedure.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  10. CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects
    Chan MY, Tan K, Tan HC, Huan PT, Li B, Phua QH, et al.
    Pharmacogenomics, 2012 Apr;13(5):533-42.
    PMID: 22462746 DOI: 10.2217/pgs.12.24
    AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians.
    Matched MeSH terms: Platelet Aggregation/drug effects; Platelet Aggregation/genetics; Platelet Aggregation Inhibitors/administration & dosage; Platelet Aggregation Inhibitors/pharmacokinetics*; Platelet Aggregation Inhibitors/pharmacology; Platelet Aggregation Inhibitors/therapeutic use
  11. Clopidogrel Vs Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis
    Tan BE, Wong PY, Baibhav B, Thakkar S, Azhar AZ, Rao M, et al.
    Curr Probl Cardiol, 2023 Aug;48(8):101174.
    PMID: 35341798 DOI: 10.1016/j.cpcardiol.2022.101174
    Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by aspirin monotherapy indefinitely. We aimed to assess the efficacy and safety of clopidogrel vs aspirin in the post-PCI population after completing DAPT. We systematically searched 5 electronic databases to identify studies comparing clopidogrel with aspirin following completion of DAPT after PCI. We pooled outcomes for major adverse cardiac events (MACE), cardiac death, all-cause death, major bleeding, myocardial infarction (MI), and stroke. We included 5 studies with 13,850 patients, of whom 5601 (40.4%) received clopidogrel. Mean follow-up was 12-36 months. All patients received drug-eluting stents. Duration of DAPT before antiplatelet monotherapy was 1-18 months. Clopidogrel was associated with reductions in MACE (Risk ratio [RR] 0.77, 95% confidence interval [CI] 0.65-0.91), any stroke (RR 0.51; 95% confidence interval [CI] 0.35-0.76), ischemic stroke (RR 0.55; 95% CI 0.32-0.94), and hemorrhagic stroke (RR 0.24; 95% CI 0.09-0.68) when compared with aspirin. Cardiac death (RR 0.87; 95% CI 0.53-1.41), all-cause death (RR 1.06; 95% CI 0.81-1.39), major bleeding (RR 0.74; 95% CI 0.43-1.29), MI (RR 1.01; 95% CI 0.64-1.60), repeat revascularization (RR 0.88; 95% CI 0.71-1.09), target vessel revascularization (RR 0.76; 95% CI 0.52-1.13), and stent thrombosis (RR 0.96; 95% CI 0.35-2.59) were not significantly different among groups. Compared with aspirin, clopidogrel was associated with reductions in MACE and stroke (ischemic and hemorrhagic) following DAPT completion after PCI. There were no significant differences in mortality, major bleeding, MI, and repeat revascularization between groups.
    Matched MeSH terms: Platelet Aggregation Inhibitors/adverse effects
  12. Fulltext Antiplatelet treatment for acute secondary prevention of non-cardioembolic minor stroke / transient ischaemic attack: an update for the acute physician
    Krishnan K, Law ZK, Minhas JS, Bath PM, Robinson TG, Sprigg N, et al.
    Clin Med (Lond), 2022 Sep;22(5):449-454.
    PMID: 36507812 DOI: 10.7861/clinmed.2021-0597
    Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  13. Fulltext Anti-inflammatory and antiplatelet activities of plasma are conserved across twelve mammalian species
    Ahmed S, Gul S, Idris F, Hussain A, Zia-Ul-Haq M, Jaafar HZ, et al.
    Molecules, 2014;19(8):11385-94.
    PMID: 25090125 DOI: 10.3390/molecules190811385
    Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.
    Matched MeSH terms: Platelet Aggregation/drug effects; Platelet Aggregation Inhibitors/pharmacology*
  14. CYP2C19 Genotype-Guided Antiplatelet Therapy Among Asian Patients with Ischaemic Stroke
    Kow CS, Zaihan AF, Hasan SS
    Clin Drug Investig, 2021 01;41(1):115-116.
    PMID: 33237558 DOI: 10.1007/s40261-020-00985-5
    Matched MeSH terms: Platelet Aggregation Inhibitors
  15. Fulltext Effect of pyridostigmine (Mestinon) on human platelet aggregation
    Leong CF, Aini-Ardena M, Cheong SK, Norris N
    Malays J Pathol, 2009 Jun;31(1):45-52.
    PMID: 19694313 MyJurnal
    Normal platelet functions are critical for achieving primary haemostasis. Numerous medications have been shown to affect platelet functions. Pyridostigmine (Mestinon), an orally active cholinesterase inhibitor that is commonly used to treat myasthenia gravis has been documented to cause epistaxis and prolonged bleeding after a cut in anectodal reports. This study was initiated after a patient diagnosed to have myasthenia gravis, developed multiple bruises a week after being started on Mestinon. The objective of this study was to investigate the effect of Mestinon on platelet aggregation stimulated with various agonists in vitro.
    Matched MeSH terms: Platelet Aggregation/drug effects*; Platelet Aggregation/physiology
  16. CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention
    Mejin M, Tiong WN, Lai LY, Tiong LL, Bujang AM, Hwang SS, et al.
    Int J Clin Pharm, 2013 Aug;35(4):621-8.
    PMID: 23661171 DOI: 10.1007/s11096-013-9783-y
    BACKGROUND: Cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms are more common in Asian populations and have been associated with diminished antiplatelet response to clopidogrel. In this era of 'personalised medicine', combining genotyping and phenotyping as a strategy to personalise antiplatelet therapy warrants further exploration.

    OBJECTIVE: This study aimed to investigate the prevalence and impact of CYP2C19*2, *3 and *17 genotypes on clopidogrel responsiveness in a multiethnic Malaysian population planned for percutaneous coronary intervention.

    SETTING: Between October 2010 and March 2011, a total of 118 consecutive patients planned for percutaneous coronary intervention were enrolled in Sarawak General Hospital, Borneo. All patients received at least 75 mg aspirin daily for at least 2 days and 75 mg clopidogrel daily for at least 4 days prior to angiography.

    METHOD: Genotyping for CYP2C19*2 (rs4244285, 681G > A), *3 (rs4986893, 636G > A) and *17 (rs11188072, -3402C > T) alleles were performed by polymerase chain reaction-restriction fragment linked polymorphism method. Whole blood ADP-induced platelet aggregation was assessed with multiple electrode platelet aggregometry (MEA) using the Multiplate Analyzer.

    MAIN OUTCOME MEASURES: The distribution of CYP2C19*2, *3 and *17 among different ethnic groups and the association between genotype, clopidogrel responsiveness and clinical outcome were the main outcome measures.

    RESULTS: The highest prevalence of poor metabolisers (carriers of at least one copy of the *2 or *3 allele) was among the Chinese (53.7 %), followed by the Malays (26.9 %), Ibans (16.4 %) and other races (3.0 %). Poor metabolisers (PMs) had the highest mean MEA (303.6 AU*min), followed by normal metabolisers (NMs) with 270.5 AU*min and extensive metabolisers (EMs) with 264.1 AU*min (p = 0.518). Among poor responders to clopidogrel, 65.2 % were PMs and NMs, respectively, whereas none were EMs (p = 0.350). Two cardiac-related deaths were reported.

    CONCLUSION: There was a diverse inter-ethnic difference in the distribution of CYP2C19 polymorphism. The findings of this study echo that of other studies where genotype appears to have a limited impact on clopidogrel responsiveness and clinical outcome in low-risk patients.

    Matched MeSH terms: Platelet Aggregation/drug effects; Platelet Aggregation Inhibitors/administration & dosage; Platelet Aggregation Inhibitors/pharmacology; Platelet Aggregation Inhibitors/therapeutic use*
  17. Fulltext Glycoprotein IIb/IIIa and P2Y12 induction by oligochitosan accelerates platelet aggregation
    Periayah MH, Halim AS, Yaacob NS, Saad AZ, Hussein AR, Rashid AH, et al.
    Biomed Res Int, 2014;2014:653149.
    PMID: 25247182 DOI: 10.1155/2014/653149
    Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro.
    Matched MeSH terms: Platelet Aggregation/drug effects; Platelet Aggregation/physiology*
  18. Classical and pleiotropic actions of dipyridamole: Not enough light to illuminate the dark tunnel?
    Balakumar P, Nyo YH, Renushia R, Raaginey D, Oh AN, Varatharajan R, et al.
    Pharmacol Res, 2014 Sep;87:144-50.
    PMID: 24861566 DOI: 10.1016/j.phrs.2014.05.008
    Dipyridamole is a platelet inhibitor indicated for the secondary prevention of transient ischemic attack. It inhibits the enzyme phosphodiesterase, elevates cAMP and cGMP levels and prevents platelet aggregation. Dipyridamole inhibits the cellular uptake of adenosine into red blood cells, platelets and endothelial cells that results in increased extracellular availability of adenosine, leading to modulation of cardiovascular function. The antiplatelet action of dipyridamole might offer therapeutic benefits in secondary stroke prevention in combination with aspirin. Inflammation and oxidative stress play an important role in atherosclerosis and thrombosis development, leading to stroke progression. Studies demonstrated anti-inflammatory, anti-oxidant and anti-proliferative actions of dipyridamole. These pleiotropic potentials of dipyridamole might contribute to improved therapeutic outcomes when used with aspirin in preventing secondary stroke. Dipyridamole was documented as a coronary vasodilator 5 decades ago. The therapeutic failure of dipyridamole as a coronary vasodilator is linked with induction of 'coronary steal' phenomenon in which by dilating resistance vessels in non-ischemic zone, dipyridamole diverts the already reduced blood flow away from the area of ischemic myocardium. Dipyridamole at high-dose could cause a marked 'coronary steal' effect. Dipyridamole, however, at low-dose could have a minimal hemodynamic effect. Low-dose dipyridamole treatment has a therapeutic potential in partially preventing diabetes mellitus-induced experimental vascular endothelial and renal abnormalities by enhancing endothelial nitric oxide signals and inducing renovascular reduction of oxidative stress. In spite of plenteous research on dipyridamole's use in clinics, its precise clinical application is still obscure. This review sheds lights on pleiotropic pharmacological actions and therapeutic potentials of dipyridamole.
    Matched MeSH terms: Platelet Aggregation Inhibitors/pharmacology; Platelet Aggregation Inhibitors/therapeutic use
  19. Genetic polymorphisms and drug interactions leading to clopidogrel resistance: why the Asian population requires special attention
    Hasan MS, Basri HB, Hin LP, Stanslas J
    Int J Neurosci, 2013 Mar;123(3):143-54.
    PMID: 23110469 DOI: 10.3109/00207454.2012.744308
    Ischemic heart disease and stroke are the two leading causes of death worldwide. Antiplatelet therapy plays the most significant role in the management of these cardiovascular and cerebrovascular occlusive events to prevent recurrent ischemic attack. Clopidogrel, an antiplatelet drug, is widely prescribed either alone or in combination with aspirin as dual antiplatelet therapy for the prevention of vascular occlusive events. The antiplatelet response to clopidogrel varies widely. Hyporesponders and nonresponders are likely to have adverse cardiovascular events during follow-up. Some drugs, such as proton pump inhibitors (omeprazole), calcium channel blockers, selective serotonin reuptake inhibitors (nefazadone), coumarin derivatives (phenprocoumon), benzodiazepines, sulfonylurea, erythromycin, and itraconazole, decrease the antiplatelet effect of clopidogrel when administered concomitantly. Decreased response to clopidogrel is common among Asians due to genetic polymorphisms associated with clopidogrel resistance, and it is nearly 70% in some of the Asian communities. It is necessary to study Asian populations, because there are a large number of Asians throughout the world due to increased migration. Current guidelines do not make genetic testing or platelet response testing mandatory prior to clopidogrel prescription. Therefore, it is important for clinicians treating Asian patients to keep in mind the interindividual variability in response to clopidogrel when prescribing the drug.
    Matched MeSH terms: Platelet Aggregation Inhibitors/metabolism*; Platelet Aggregation Inhibitors/pharmacology
  20. Statements of the Malaysian Society of Gastroenterology & Hepatology and the National Heart Association of Malaysia task force 2012 working party on the use of antiplatelet therapy and proton pump inhibitors in the prevention of gastrointestinal bleeding
    Tan HJ, Mahadeva S, Menon J, Ng WK, Zainal Abidin I, Chan FK, et al.
    J Dig Dis, 2013 Jan;14(1):1-10.
    PMID: 23134105 DOI: 10.1111/1751-2980.12000
    The working party statements aim to provide evidence and guidelines to practising doctors on the use of antiplatelet therapy and proton pump inhibitors (PPIs) in patients with cardiovascular risk as well as those at risk of gastrointestinal (GI) bleeding. Balancing the GI and cardiovascular risk and benefits of antiplatelet therapy and PPIs may sometimes pose a significant challenge to doctors. Concomitant use of anti-secretory medications has been shown to reduce the risk of GI bleeding but concerns have been raised on the potential interaction of PPIs and clopidogrel. Many new data have emerged on this topic but some can be confusing and at times controversial. These statements examined the supporting evidence in four main areas: rationale for antiplatelet therapy, risk factors of GI bleeding, PPI-clopidogrel interactions and timing for recommencing antiplatelet therapy after GI bleeding, and made appropriate recommendations.
    Matched MeSH terms: Platelet Aggregation Inhibitors/adverse effects; Platelet Aggregation Inhibitors/therapeutic use*
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