Displaying publications 1 - 20 of 47 in total

Abstract:
Sort:
  1. Fulltext Use of ticagrelor alongside fibrinolytic therapy in patients with ST-segment elevation myocardial infarction: Practical perspectives based on data from the TREAT study
    Berwanger O, Abdelhamid M, Alexander T, Alzubaidi A, Averkov O, Aylward P, et al.
    Clin Cardiol, 2018 Oct;41(10):1322-1327.
    PMID: 30098028 DOI: 10.1002/clc.23043
    Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-segment elevation myocardial infarction (STEMI). In patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive treatment is recommended, comprising immediate fibrinolytic therapy with subsequent coronary angiography and rescue PCI if needed. Improving clinical outcomes following fibrinolysis remains of great importance for the many patients globally for whom rapid treatment with primary PCI is not possible. For patients with acute coronary syndrome who underwent primary PCI, the PLATO trial demonstrated superior efficacy of ticagrelor relative to clopidogrel. Results in the predefined subgroup of patients with STEMI were consistent with the overall PLATO trial. Patients who received fibrinolytic therapy in the 24 hours before randomization were excluded from PLATO, and there is thus a lack of data on the safety of using ticagrelor in conjunction with fibrinolytic therapy in the first 24 hours after STEMI. The TREAT study addresses this knowledge gap; patients with STEMI who had symptom onset within the previous 24 hours and had received fibrinolytic therapy (of whom 89.4% had also received clopidogrel) were randomized to treatment with ticagrelor or clopidogrel (median time between fibrinolysis and randomization: 11.5 hours). At 30 days, ticagrelor was found to be non-inferior to clopidogrel for the primary safety outcome of Thrombolysis in Myocardial Infarction (TIMI)-defined first major bleeding. Considering together the results of the PLATO and TREAT studies, initiating or switching to treatment with ticagrelor within the first 24 hours after STEMI in patients receiving fibrinolysis is reasonable.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  2. Case Report: Ocular Tilt Reaction with Internuclear Ophthalmoplegia and Multiple Cranial Nerve Palsies
    Teo SK, Mohd Khialdin S, Yong MH, Othman O, Ami M
    Optom Vis Sci, 2020 Dec;97(12):1018-1022.
    PMID: 33252541 DOI: 10.1097/OPX.0000000000001607
    SIGNIFICANCE: Ocular tilt reaction (OTR) is an abnormal eye-head postural reaction that consists of skew deviation, head tilt, and bilateral ocular torsion. Understanding of the pathway of the vestibulo-ocular reflex (VOR) is essential because this will help to localize the pathology.

    PURPOSE: The aim of this study was to report a case of OTR with contralateral internuclear ophthalmoplegia (INO) and fifth and seventh cranial nerve palsies.

    CASE REPORT: A 51-year-old gentleman with underlying diabetes mellitus presented with sudden onset of diplopia for 3 days. On examination, his visual acuity was 20/30 bilaterally without a relative afferent pupillary defect. He had a right OTR consisting of a right head tilt, a skew deviation with a left eye hypertropia, and bilateral ocular torsion (right excyclotorsion and left incyclotorsion) with nystagmus. He also had a left adduction deficit and right abduction nystagmus consistent with a left INO. Ocular examination revealed evidence of proliferative diabetic retinopathy bilaterally. Two days after the initial presentation, the patient developed left seventh and fifth cranial nerve palsies. MRI showed left pontine infarction and multiple chronic lacunar infarctions. There was an incidental finding of a vascular loop compression on cisternal portions of the left trigeminal, facial, and vestibulocochlear nerves. Antiplatelet treatment was started on top of a better diabetic control. The diplopia was gradually resolved with improved clinical signs. In this case, the left pontine infarction had likely affected the terminal decussated part of the vestibulocochlear nerve from the right VOR pathway, medial longitudinal fasciculus, and cranial nerve nuclei in the left pons.

    CONCLUSIONS: The OTR can be ipsilateral to the lesion if the lesion is before the decussation of the VOR pathway in the pons, or it can be contralateral to the lesion if the lesion is after the decussation. In case of an OTR that is associated with contralateral INO and other contralateral cranial nerves palsy, a pathology in the pons that is contralateral to the OTR should be considered. Neuroimaging study can hence be targeted to identify the possible cause.

    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  3. 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
  4. Fulltext Invasive and antiplatelet treatment of patients with non-ST-segment elevation myocardial infarction: Understanding and addressing the global risk-treatment paradox
    Ahrens I, Averkov O, Zúñiga EC, Fong AYY, Alhabib KF, Halvorsen S, et al.
    Clin Cardiol, 2019 Oct;42(10):1028-1040.
    PMID: 31317575 DOI: 10.1002/clc.23232
    Clinical guidelines for the treatment of patients with non-ST-segment elevation myocardial infarction (NSTEMI) recommend an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization. However, although patients with NSTEMI have a higher long-term mortality risk than patients with ST-segment elevation myocardial infarction (STEMI), they are often treated less aggressively; with those who have the highest ischemic risk often receiving the least aggressive treatment (the "treatment-risk paradox"). Here, using evidence gathered from across the world, we examine some reasons behind the suboptimal treatment of patients with NSTEMI, and recommend approaches to address this issue in order to improve the standard of healthcare for this group of patients. The challenges for the treatment of patients with NSTEMI can be categorized into four "P" factors that contribute to poor clinical outcomes: patient characteristics being heterogeneous; physicians underestimating the high ischemic risk compared with bleeding risk; procedure availability; and policy within the healthcare system. To address these challenges, potential approaches include: developing guidelines and protocols that incorporate rigorous definitions of NSTEMI; risk assessment and integrated quality assessment measures; providing education to physicians on the management of long-term cardiovascular risk in patients with NSTEMI; and making stents and antiplatelet therapies more accessible to patients.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  5. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease
    Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al.
    N Engl J Med, 2017 10 05;377(14):1319-1330.
    PMID: 28844192 DOI: 10.1056/NEJMoa1709118
    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.

    METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.

    RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.

    CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  6. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial
    Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, et al.
    Lancet, 2018 01 20;391(10117):205-218.
    PMID: 29132879 DOI: 10.1016/S0140-6736(17)32458-3
    BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.

    METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.

    FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).

    INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.

    FUNDING: Bayer AG.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  7. Clinical use of clopidogrel in acute coronary syndrome
    Zambahari R, Kwok OH, Javier S, Mak KH, Piyamitr S, Tri Ho HQ, et al.
    Int J Clin Pract, 2007 Mar;61(3):473-81.
    PMID: 17313616
    Several therapeutic approaches have been developed to improve the outcome among patients with acute coronary syndrome (ACS). However, treatment with antithrombotic therapies such as oral glycoprotein IIb/IIIa inhibitors has been limited by the lack of efficacy and excess bleeding complications. As the publication of the landmark study Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), the clinical benefit of early and intermediate-term use of combined antiplatelet agents--clopidogrel plus aspirin--in non-ST-segment elevation myocardial infarction (NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoing percutaneous coronary intervention (PCI) was further supported by the PCI-CURE trial. Recently, the results of two major trials Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28, Clopidogrel and Metoprolol in Myocardial Infarction Trial established the pivotal role of clopidogrel in the other spectrum of ACS-STEMI. Coupled with the results from previous multicentre trials, these two studies provide a guide for the early and long-term use of clopidogrel in the whole spectrum of ACS. A review summarising the results of the recent clinical trials and a discussion on its implications for the clinical management of ACS is presented.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  8. 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/therapeutic use
  9. Fulltext The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications
    Viecelli AK, Pascoe E, Polkinghorne KR, Hawley C, Paul-Brent PA, Badve SV, et al.
    BMC Nephrol, 2015;16:89.
    PMID: 26116581 DOI: 10.1186/s12882-015-0089-2
    The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  10. Fulltext Evaluation of medication use in Malaysian predialysis patients
    Salman M, Khan AH, Adnan AS, Syed Sulaiman SA, Shehzadi N, Asif N, et al.
    Saudi J Kidney Dis Transpl, 2017 5 26;28(3):517-523.
    PMID: 28540887 DOI: 10.4103/1319-2442.206451
    Chronic kidney disease (CKD) patients suffer from multiple comorbidities and complications as a cause or consequence of kidney disease. Information regarding medication- prescribing patterns in predialysis patients is sparse. We conducted a retrospective study to evaluate the medication prescription patterns among predialysis patients. Medical records (both paper based and computerized) of patients at CKD Resource Centre, Hospital Universiti Sains Malaysia, were reviewed. A total of 615 eligible cases were included in the study. The mean number of medications prescribed per patient was 8.22 ± 2.81, and medication use was correlated to the renal function (stage 3a < stage 3b < stage 4 < stage 5; P <0.001). The top three prescribed medication groups were found to be lipid-lowering agents, calcium channel blockers, and antiplatelet agents. Some medication classes such as nonaluminum/noncalcium phosphate binders, erythropoietin-stimulating agents, and renin-angiotensin-aldosterone system blockers, particularly in advanced stage, were found to be underutilized. In conclusion, predialysis patients are prescribed a large number of medications. Our findings highlight the need for assessing the impact of current medication-prescribing patterns on morbidity and mortality rates in Malaysian predialysis population.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  11. 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 Inhibitors/therapeutic use*
  12. Late stent thrombosis in a patient with CYP2C19*3/*17 genotype and clopidogrel high on-treatment platelet reactivity
    Tan SSN, Koh KT, Tiong LL, Ong TK, Fong AYY
    Pharmacogenomics, 2018 10;19(15):1151-1157.
    PMID: 30191759 DOI: 10.2217/pgs-2018-0082
    AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in patient's post percutaneous coronary intervention (PCI) could be attributed to high on-treatment platelet reactivity.

    METHODS: A 44-year-old male, who had staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI. Platelet function testing and genotyping showed clopidogrel high on-treatment platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced.

    RESULTS & CONCLUSION: This case study is the first reported in Malaysia to document a patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an uncomplicated index PCI procedure.

    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  13. Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment
    Islam MA, Alam F, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(28):4451-69.
    PMID: 27229722
    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear. Therefore, patients are treated with anticoagulant and/or antiplatelet regimens just as in other thrombotic disorders even though the thrombotic pathophysiology is mainly aPLs-mediated. In this review, we provided an update of the cellular, auto-immune and genetic factors known to play important roles in the generation of thrombi. Current successful regimens are also outlined along with potential emerging treatment strategies that may lead to the optimum management of thrombotic APS patients.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  14. Thrombotic management of antiphospholipid syndrome: towards novel targeted therapies
    Islam MA, Alam F, Wong KK, Kamal MA, Gan SH
    Curr Vasc Pharmacol, 2017;15(4):313-326.
    PMID: 28056758 DOI: 10.2174/1570161115666170105120931
    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  15. Fulltext The use of antiplatelet agents for arterial thromboprophylaxis in COVID-19
    Kow CS, Hasan SS
    Rev Esp Cardiol (Engl Ed), 2021 01;74(1):114-115.
    PMID: 32933883 DOI: 10.1016/j.rec.2020.08.009
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  16. 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
  17. 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*
  18. Fulltext The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD)
    Akkaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, et al.
    Molecules, 2021 Apr 01;26(7).
    PMID: 33915807 DOI: 10.3390/molecules26071987
    Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use
  19. Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis
    Biswas M, Kali MSK, Biswas TK, Ibrahim B
    Platelets, 2021 Jul 04;32(5):591-600.
    PMID: 32664772 DOI: 10.1080/09537104.2020.1792871
    The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45-0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25-0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44-0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43-1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38-1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13-2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.28-2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88-1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
  20. 1H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients
    Amin AM, Sheau Chin L, Teh CH, Mostafa H, Mohamed Noor DA, Sk Abdul Kader MA, et al.
    J Pharm Biomed Anal, 2017 Nov 30;146:135-146.
    PMID: 28873361 DOI: 10.1016/j.jpba.2017.08.018
    Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using 1H NMR analysis to phenotype clopidogrel HTPR in urine. Urine samples were collected from 71 coronary artery disease (CAD) patients who were planned for interventional angiographic procedure prior to taking 600mg clopidogrel loading dose (LD) and 6h post LD. Patients' platelets function testing was assessed with the VerifyNow® P2Y12 assay at 6h after LD. Urine samples were analysed using 1H NMR. Multivariate statistical analysis was used to identify metabolites associated with clopidogrel HTPR. In pre-dose samples, 16 metabolites were associated with clopidogrel HTPR. However, 18 metabolites were associated with clopidogrel HTPR in post-dose samples. The pathway analysis of the identified biomarkers reflected that multifactorial conditions are associated with clopidogrel HTPR. It also revealed the implicated role of gut microbiota in clopidogrel HTPR. Pharmacometabolomics not only discovered novel biomarkers of clopidogrel HTPR but also revealed implicated pathways and conditions.
    Matched MeSH terms: Platelet Aggregation Inhibitors/therapeutic use*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links