Genomes and Genes
platelet aggregation inhibitors
Summary: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
- Roberts J, Wells G, Le May M, Labinaz M, Glover C, Froeschl M, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet. 2012;379:1705-11 pubmed publisher..Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity. Spartan Biosciences. ..
- Lip G, Ponikowski P, Andreotti F, Anker S, Filippatos G, Homma S, et al. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm. A joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Eur J Heart Fail. 2012;14:681-95 pubmed publisher..New oral anticoagulants that offer a different risk-benefit profile compared with warfarin may appear as an attractive therapeutic option, but this would need to be confirmed in clinical trials. ..
- Nikolic E, Janzon M, Hauch O, Wallentin L, Henriksson M. Cost-effectiveness of treating acute coronary syndrome patients with ticagrelor for 12 months: results from the PLATO study. Eur Heart J. 2013;34:220-8 pubmed publisher..ClinicalTrials.gov Identifier: NCT00391872. ..
- Grove E, Storey R, Würtz M. Platelet function testing in atherothrombotic disease. Curr Pharm Des. 2012;18:5379-91 pubmed
- Liao Y, Leu Y, Chan Y, Kuo P, Wu T. Anti-platelet aggregation and vasorelaxing effects of the constituents of the rhizomes of Zingiber officinale. Molecules. 2012;17:8928-37 pubmed publisher..According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism. ..
- Kennedy F, Lanfranconi S, Hicks C, Reid J, Gompertz P, Price C, et al. Antiplatelets vs anticoagulation for dissection: CADISS nonrandomized arm and meta-analysis. Neurology. 2012;79:686-9 pubmed publisher..The nonrandomized CADISS data show a lower rate of recurrent stroke than reported in some previous studies. www.dissection.co.uk, ISRNCTN44555237. ..
- Lordkipanidzé M. Advances in monitoring of aspirin therapy. Platelets. 2012;23:526-36 pubmed
- Součková L, Opatrilova R, Suk P, Cundrle I, Pavlik M, Zvonicek V, et al. Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). Eur J Clin Pharmacol. 2013;69:309-17 pubmed publisher..Therefore, other drugs, preferentially administered intravenously, should be considered. ..
- Dansette P, Rosi J, Debernardi J, Bertho G, Mansuy D. Metabolic activation of prasugrel: nature of the two competitive pathways resulting in the opening of its thiophene ring. Chem Res Toxicol. 2012;25:1058-65 pubmed publisher..Chemical experiments have confirmed that hydrolytic opening of thiolactone 2c exclusively leads to derivatives of the endo thiol isomer 3c endo. ..
- Endale M, Lee W, Kamruzzaman S, Kim S, Park J, Park M, et al. Ginsenoside-Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation. Br J Pharmacol. 2012;167:109-27 pubmed publisher..These data suggest that G-Rp1 may have therapeutic potential for the treatment of cardiovascular diseases involving aberrant platelet activation. ..
- Roe M, Armstrong P, Fox K, White H, Prabhakaran D, Goodman S, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367:1297-309 pubmed publisher..Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.). ..
- Langer H, Choi E, Zhou H, Schleicher R, Chung K, Tang Z, et al. Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis. Circ Res. 2012;110:1202-10 pubmed publisher..Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment. ..
- Sadanandan S, Singh I. Clopidogrel: the data, the experience, and the controversies. Am J Cardiovasc Drugs. 2012;12:361-74 pubmed publisher..This review discusses these ongoing controversies regarding the optimal use of dual antiplatelet therapy with aspirin and clopidogrel in patients with ACS or those undergoing PCI. ..
- Bhatt D, Pare G, Eikelboom J, Simonsen K, Emison E, Fox K, et al. The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study. Eur Heart J. 2012;33:2143-50 pubmed..This study is registered with ClinicalTrials.gov number, NCT00050817. ..
- Al Azzam S, Alzoubi K, Khabour O, Alowidi A, Tawalbeh D. The prevalence and factors associated with aspirin resistance in patients premedicated with aspirin. Acta Cardiol. 2012;67:445-8 pubmed..05). The incidence of aspirin resistance is high in the Jordanian population. Aspirin resistance is associated with female gender and diabetes. On the other hand, the use of statins improves response to aspirin. ..
- Lewis J, Horenstein R, Ryan K, O Connell J, Gibson Q, Mitchell B, et al. The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genomics. 2013;23:1-8 pubmed publisher..Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel. ..
- Brighton T, Eikelboom J, Mann K, Mister R, Gallus A, Ockelford P, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367:1979-87 pubmed publisher..Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism...
- Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation. 2012;125:2015-26 pubmed publisher..URL: http://www.clinicaltrials.gov. Unique identifier: NCT00611286. ..
- Sambu N, Radhakrishnan A, Dent H, Calver A, Corbett S, Gray H, et al. Personalised antiplatelet therapy in stent thrombosis: observations from the Clopidogrel Resistance in Stent Thrombosis (CREST) registry. Heart. 2012;98:706-11 pubmed publisher..Improved APT efficacy can be achieved by tailored therapy. Short TEG is a plausible platelet function test that can be used to deliver point of care personalised APT. ..
- Alexopoulos D, Xanthopoulou I, Gkizas V, Kassimis G, Theodoropoulos K, Makris G, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2012;5:797-804 pubmed publisher..Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment-elevation myocardial infarction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163. ..
- Bhatt D, Stone G, Mahaffey K, Gibson C, Steg P, Hamm C, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303-13 pubmed publisher..Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.). ..
- Andersson T, Morrison D, Nagy P, Pisupati J, Schettler J, Warner T. Evaluation of the pharmacodynamics of acetylsalicylic acid 81 mg with or without esomeprazole 20 mg in healthy volunteers. Am J Cardiovasc Drugs. 2012;12:217-24 pubmed publisher..88, 1.29). The combination of ASA and esomeprazole was well tolerated. No pharmacodynamic interaction between low-dose ASA and esomeprazole was found with regard to platelet function. Registered at ClinicalTrials. gov as NCT01199328. ..
- Price M, Murray S, Angiolillo D, Lillie E, Smith E, Tisch R, et al. Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012;59:1928-37 pubmed publisher..Genotype Information and Functional Testing Study [GIFT]; NCT00992420). ..
- Siller Matula J, Trenk D, Schror K, Gawaz M, Kristensen S, Storey R, et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013;6:1111-28 pubmed publisher..Moreover, this paper discusses randomized trials, which so far have failed to show that tailored antiplatelet therapy improves clinical outcome, and treatment options for patients with high on-treatment platelet reactivity. ..
- Tobin W, Kinsella J, Coughlan T, Collins D, O NEILL D, Murphy R, et al. High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study. Eur J Neurol. 2013;20:344-52 pubmed publisher..The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain...
- Sharma R, Voelker D, Sharma R, Reddy H, Dod H, Marsh J. Evolving role of platelet function testing in coronary artery interventions. Vasc Health Risk Manag. 2012;8:65-75 pubmed publisher..While we wait for definitive trials, a predictive prognostic algorithm is necessary to individualize antiplatelet therapy with P2Y12 inhibitors based on platelet function assays and genetic testing. ..
- Collet J, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012;367:2100-9 pubmed publisher..Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.). ..
- Freynhofer M, Bruno V, Wojta J, Huber K. The role of platelets in athero-thrombotic events. Curr Pharm Des. 2012;18:5197-214 pubmed
- Azmoon S, Angiolillo D. Switching antiplatelet regimens: alternatives to clopidogrel in patients with acute coronary syndrome undergoing PCI: a review of the literature and practical considerations for the interventional cardiologist. Catheter Cardiovasc Interv. 2013;81:232-42 pubmed publisher..This article provides an overview of the literature on switching antiplatelet treatment strategies and practical considerations for the interventional cardiologist. ..
- Stone G, Maehara A, Witzenbichler B, Godlewski J, Parise H, Dambrink J, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA. 2012;307:1817-26 pubmed publisher..Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy...
- Haraguchi K, Miyachi S, Izumi T, Matsubara N, Naito T, Asai T, et al. [Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention]. No Shinkei Geka. 2012;40:399-406 pubmed..With aneurysmal transarterial embolization, thromboembolic events tended to occur among clopidogrel low-responders. Addition of cilostazol may offer one method of overcoming clopidogrel resistance. ..
- Reese E, Daniel Mullins C, Beitelshees A, Onukwugha E. Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of antiplatelet therapy with clopidogrel or prasugrel. Pharmacotherapy. 2012;32:323-32 pubmed publisher..Genotype-guided antiplatelet therapy selection may be more cost-effective and may provide more clinical value due to fewer adverse outcomes. ..
- Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor. Clin Pharmacokinet. 2012;51:305-18 pubmed publisher..This article summarizes our current knowledge regarding the pharmacokinetic, pharmacodynamic and pharmacogenetic profile of ticagrelor. ..
- Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366:1959-67 pubmed publisher..Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown...
- Saucedo J. Antiplatelet therapy for patients with diabetes mellitus and acute coronary syndrome. Prim Care Diabetes. 2012;6:167-77 pubmed publisher..Similar clinical benefits are seen with ticagrelor versus clopidogrel in patients with and without diabetes. Evidence suggests that prasugrel/aspirin may provide particular advantages for patients with diabetes mellitus. ..
- Valgimigli M, Tebaldi M, Campo G, Gambetti S, Bristot L, Monti M, et al. Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By dr. JACC Cardiovasc Interv. 2012;5:268-77 pubmed publisher..Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse [The FABOLUS PRO trial]; NCT01336348). ..
- Morrow D, Braunwald E, Bonaca M, Ameriso S, Dalby A, Fish M, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404-13 pubmed publisher..However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.). ..
- Dans A, Connolly S, Wallentin L, Yang S, Nakamya J, Brueckmann M, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127:634-40 pubmed publisher..URL: http://clinicaltrials.gov. Unique identifier: NCT00262600. ..
- Reny J, Combescure C, Daali Y, Fontana P. Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis. J Thromb Haemost. 2012;10:1242-51 pubmed publisher..This meta-analysis suggests that the PON1-Q192R polymorphism has no major impact on the risk of MACE and does not alter the biological response to clopidogrel in clopidogrel-treated patients. ..
- Gurbel P, Bliden K, Logan D, Kereiakes D, Lasseter K, White A, et al. The influence of smoking status on the pharmacokinetics and pharmacodynamics of clopidogrel and prasugrel: the PARADOX study. J Am Coll Cardiol. 2013;62:505-12 pubmed publisher..The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease; NCT01260584). ..
- Würtz M, Grove E. Interindividual variability in the efficacy of oral antiplatelet drugs: definitions, mechanisms and clinical importance. Curr Pharm Des. 2012;18:5344-61 pubmed..This article provides an integrated review of interindividual variability in the efficacy of aspirin and clopidogrel with particular emphasis on possible effect-modifying mechanisms and clinical implications. ..
- Hankey G, Eikelboom J, Yi Q, Lees K, Chen C, Xavier D, et al. Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial. Lancet Neurol. 2012;11:512-20 pubmed publisher..Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, and Singapore National Medical Research Council. ..
- Alexopoulos D, Galati A, Xanthopoulou I, Mavronasiou E, Kassimis G, Theodoropoulos K, et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: a pharmacodynamic study. J Am Coll Cardiol. 2012;60:193-9 pubmed publisher..Ticagrelor Versus Prasugrel in Acute Coronary Syndromes After Percutaneous Coronary Intervention; NCT01360437). ..
- Trenk D, Stone G, Gawaz M, Kastrati A, Angiolillo D, Müller U, et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet React. J Am Coll Cardiol. 2012;59:2159-64 pubmed publisher..However, given the low rate of adverse ischemic events after PCI with contemporary DES in stable CAD, the clinical utility of this strategy could not be demonstrated. ..
- Burness C, Scott L. Acetylsalicylic acid/esomeprazole fixed-dose combination. Drugs Aging. 2012;29:233-242 pubmed publisher..Low-dose ASA plus esomeprazole treatment was generally well tolerated, with a similar adverse event profile to that seen with low-dose ASA plus placebo. ..
- Zinkstok S, Roos Y. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet. 2012;380:731-7 pubmed publisher..The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase. The Dutch Heart Foundation. ..
- Casado Arroyo R, Polo Tomas M, Roncalés M, Scheiman J, Lanas A. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart. 2012;98:718-23 pubmed publisher..This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population. ..
- Andersson C, Lyngbæk S, Nguyen C, Nielsen M, Gislason G, Køber L, et al. Association of clopidogrel treatment with risk of mortality and cardiovascular events following myocardial infarction in patients with and without diabetes. JAMA. 2012;308:882-9 pubmed publisher..Among patients with diabetes compared with patients without diabetes, the use of conventional clopidogrel treatment after MI was associated with lower reduction in the risk of all-cause death and cardiovascular death. ..
- Brener S, Cristea E, Kirtane A, McEntegart M, Xu K, Mehran R, et al. Intra-procedural stent thrombosis: a new risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention for acute coronary syndromes. JACC Cardiovasc Interv. 2013;6:36-43 pubmed publisher..Intra-procedural ST should be considered as a distinct category of ST and routinely reported, particularly for ACS patients. ..
- Maggioni A, Anker S, Dahlstrom U, Filippatos G, Ponikowski P, Zannad F, et al. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2013;15:1173-84 pubmed publisher..Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. ..
- Roe M, White J, Kaul P, Tricoci P, Lokhnygina Y, Miller C, et al. Regional patterns of use of a medical management strategy for patients with non-ST-segment elevation acute coronary syndromes: insights from the EARLY ACS Trial. Circ Cardiovasc Qual Outcomes. 2012;5:205-13 pubmed publisher..These findings have important implications for the conduct of future clinical trials, and highlight global similarities in the profile and prognosis of medically managed NSTE ACS patients. ..
- Armstrong P, Peter K. GPIIb/IIIa inhibitors: from bench to bedside and back to bench again. Thromb Haemost. 2012;107:808-14 pubmed publisher..This overview will review the physiology behind the inherent problems of a ligand-based integrin inhibitor design and discuss novel promising approaches for GPIIb/IIIa inhibition. ..
- Mangiacapra F, Patti G, Barbato E, Peace A, Ricottini E, Vizzi V, et al. A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome . JACC Cardiovasc Interv. 2012;5:281-9 pubmed publisher..Adjunctive measures may be beneficial in patients with higher or lower platelet reactivity in order to improve clinical outcomes after PCI. ..
- Dreischulte T, Grant A, Donnan P, McCowan C, Davey P, Petrie D, et al. A cluster randomised stepped wedge trial to evaluate the effectiveness of a multifaceted information technology-based intervention in reducing high-risk prescribing of non-steroidal anti-inflammatory drugs and antiplatelets in primary medical care: t. Implement Sci. 2012;7:24 pubmed publisher..ClinicalTrials.gov, dossier number: NCT01425502. ..
- Cornel J, Becker R, Goodman S, Husted S, Katus H, Santoso A, et al. Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2012;164:334-342.e1 pubmed publisher..The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits. ..
- Focks J, Brouwer M, van Oijen M, Lanas A, Bhatt D, Verheugt F. Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review. Heart. 2013;99:520-7 pubmed publisher..This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data. ..
- Naka H, Nomura E, Kitamura J, Imamura E, Wakabayashi S, Matsumoto M. Antiplatelet therapy as a risk factor for microbleeds in intracerebral hemorrhage patients: analysis using specific antiplatelet agents. J Stroke Cerebrovasc Dis. 2013;22:834-40 pubmed publisher..986; 95% CI 1.000-3.946; P = .0501). Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results. ..
- Kalantzi K, Tsoumani M, Goudevenos I, Tselepis A. Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives. Expert Rev Clin Pharmacol. 2012;5:319-36 pubmed publisher..Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects. ..
- Pulley J, Denny J, Peterson J, Bernard G, Vnencak Jones C, Ramirez A, et al. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012;92:87-95 pubmed publisher..The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine. ..