Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Review Article

Cardiovascular Risk of Synthetic, Non-Biologic Disease-Modifying Anti- Rheumatic Drugs (DMARDs)

Author(s): Iordanis S. Mourouzis*, Antonis S. Manolis and Constantinos Pantos

Volume 18, Issue 5, 2020

Page: [455 - 462] Pages: 8

DOI: 10.2174/1570161117666190930113837

Price: $65

conference banner
Abstract

Patients with rheumatoid diseases have an increased risk of cardiovascular disease (CVD) and CVD-related death compared with the general population. Both the traditional cardiovascular risk factors and systemic inflammation are contributors to this phenomenon. This review examines the available evidence about the effects of synthetic, non-biologic disease-modifying antirheumatic drugs (DMARDs) on CVD risk. This is an important issue for clinicians when deciding on individual treatment plans in patients with rheumatic diseases. Evidence suggests that synthetic, non-biologic DMARDs such as methotrexate, sulfasalazine, hydroxychloroquine, leflunomide and tofacitinib show decreased CVD morbidity and mortality. However, the strongest data in favour of a reduction in CVD events in rheumatoid patients are shown with methotrexate, which has been the focus of most studies. Adequate proof for a favourable effect also exists for hydroxychloroquine. Larger, prospective studies and randomized clinical trials are needed to better characterize the effect of synthetic, non-biologic DMARDs on CVD outcomes in these patients. Design of future studies should include areas with lack of evidence, such as the risk for heart failure, arrhythmias and valvular heart disease. The clinically relevant question whether synthetic, non-biologic DMARDs are inferior to biologic DMARDs in terms of CVD outcomes remains not adequately addressed.

Keywords: Cardiovascular risk, rheumatoid diseases, disease-modifying antirheumatic drugs, methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, tofacitinib.

Graphical Abstract
[1]
Meune C, Touzé E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a system-atic review and meta-analysis of cohort studies. Rheumatology (Oxford) 2009; 48(10): 1309-13.
[http://dx.doi.org/10.1093/rheumatology/kep252] [PMID: 19696061]
[2]
Peters MJ, Symmons DP, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69(2): 325-31.
[http://dx.doi.org/10.1136/ard.2009.113696] [PMID: 19773290]
[3]
Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59(12): 1690-7.
[http://dx.doi.org/10.1002/art.24092] [PMID: 19035419]
[4]
Corrao S, Messina S, Pistone G, Calvo L, Scaglione R, Licata G. Heart involvement in rheumatoid arthritis: systematic review and meta-analysis. Int J Cardiol 2013; 167(5): 2031-8.
[http://dx.doi.org/10.1016/j.ijcard.2012.05.057] [PMID: 22703938]
[5]
Lindhardsen J, Ahlehoff O, Gislason GH, et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis 2011; 70(6): 929-34.
[http://dx.doi.org/10.1136/ard.2010.143396] [PMID: 21389043]
[6]
Semb AG, Kvien TK, Aastveit AH, et al. Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study. Ann Rheum Dis 2010; 69(11): 1996-2001.
[http://dx.doi.org/10.1136/ard.2009.126128] [PMID: 20551156]
[7]
Choy E, Ganeshalingam K, Semb AG, Szekanecz Z, Nurmohamed M. Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology (Oxford) 2014; 53(12): 2143-54.
[http://dx.doi.org/10.1093/rheumatology/keu224] [PMID: 24907149]
[8]
Van Doornum S, Brand C, King B, Sundararajan V. Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54(7): 2061-8.
[http://dx.doi.org/10.1002/art.21932] [PMID: 16802340]
[9]
Løgstrup BB, Ellingsen T, Pedersen AB, Kjaersgaard A, Bøtker HE, Maeng M. Development of heart failure in patients with rheumatoid arthritis: A Danish population-based study. Eur J Clin Invest 2018; 48(5)e12915
[http://dx.doi.org/10.1111/eci.12915] [PMID: 29464714]
[10]
Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years. Arthritis Rheum 2005; 52(2): 412-20.
[http://dx.doi.org/10.1002/art.20855] [PMID: 15692992]
[11]
Wolfe F, Michaud K. Heart failure in rheumatoid arthritis: rates, predictors, and the effect of anti-tumor necrosis factor therapy. Am J Med 2004; 116(5): 305-11.
[http://dx.doi.org/10.1016/j.amjmed.2003.09.039] [PMID: 14984815]
[12]
Crowson CS, Nicola PJ, Kremers HM, et al. How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease? Arthritis Rheum 2005; 52(10): 3039-44.
[http://dx.doi.org/10.1002/art.21349] [PMID: 16200583]
[13]
Roldan CA, DeLong C, Qualls CR, Crawford MH. Characterization of valvular heart disease in rheumatoid arthritis by transesophageal echo-cardiography and clinical correlates. Am J Cardiol 2007; 100(3): 496-502.
[http://dx.doi.org/10.1016/j.amjcard.2007.03.048] [PMID: 17659935]
[14]
Miller AM, McInnes IB. Cytokines as therapeutic targets to reduce cardiovascular risk in chronic inflammation. Curr Pharm Des 2011; 17(1): 1-8.
[http://dx.doi.org/10.2174/138161211795049796] [PMID: 21222645]
[15]
Waehre T, Yndestad A, Smith C, et al. Increased expression of interleukin-1 in coronary artery disease with downregulatory effects of HMG-CoA reductase inhibitors. Circulation 2004; 109(16): 1966-72.
[http://dx.doi.org/10.1161/01.CIR.0000125700.33637.B1] [PMID: 15051633]
[16]
Rho YH, Chung CP, Oeser A, et al. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2009; 61(11): 1580-5.
[http://dx.doi.org/10.1002/art.25009] [PMID: 19877084]
[17]
Ntari L, Sakkou M, Chouvardas P, et al. Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis. Ann Rheum Dis 2018; 77(6): 926-34.
[http://dx.doi.org/10.1136/annrheumdis-2017-212597] [PMID: 29475857]
[18]
Lazúrová I, Tomáš Ľ. Cardiac impairment in rheumatoid arthritis and influence of anti-TNFα treatment. Clin Rev Allergy Immunol 2017; 52(3): 323-32.
[http://dx.doi.org/10.1007/s12016-016-8566-3] [PMID: 27342458]
[19]
Lacaille D, Avina-Zubieta JA, Sayre EC, Abrahamowicz M. Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population-closing the mortality gap. Ann Rheum Dis 2017; 76(6): 1057-63.
[http://dx.doi.org/10.1136/annrheumdis-2016-209562] [PMID: 28031164]
[20]
Arts EE, Fransen J, Den Broeder AA, van Riel PLCM, Popa CD. Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study. Ann Rheum Dis 2017; 76(10): 1693-9.
[http://dx.doi.org/10.1136/annrheumdis-2016-210997] [PMID: 28606965]
[21]
Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74(3): 480-9.
[http://dx.doi.org/10.1136/annrheumdis-2014-206624] [PMID: 25561362]
[22]
Brown PM, Pratt AG, Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat Rev Rheumatol 2016; 12(12): 731-42.
[http://dx.doi.org/10.1038/nrrheum.2016.175] [PMID: 27784891]
[23]
Brody M, Böhm I, Bauer R. Mechanism of action of methotrexate: experimental evidence that methotrexate blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target cells. Eur J Clin Chem Clin Biochem 1993; 31(10): 667-74.
[http://dx.doi.org/10.1515/cclm.1993.31.10.667] [PMID: 8292668]
[24]
Methotrexate Side Effects in Detail. https://www.drugs.com/sfx/methotrexate-side-effects.html
[25]
Yoshino T, Nishida H, Takita T, et al. A report of 2 cases of disseminated invasive aspergillosis with myocarditis in immunocompromised patients. Open J Pathol 2013; 3: 166-9.
[http://dx.doi.org/10.4236/ojpathology.2013.34030]
[26]
Choi HK, Hernán MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359(9313): 1173-7.
[http://dx.doi.org/10.1016/S0140-6736(02)08213-2] [PMID: 11955534]
[27]
Westlake SL, Colebatch AN, Baird J, et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford) 2010; 49(2): 295-307.
[http://dx.doi.org/10.1093/rheumatology/kep366] [PMID: 19946022]
[28]
van Halm VP, Nurmohamed MT, Twisk JW, Dijkmans BA, Voskuyl AE. Disease-modifying antirheumatic drugs are associated with a re-duced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study. Arthritis Res Ther 2006; 8(5): R151.
[http://dx.doi.org/10.1186/ar2045] [PMID: 16984661]
[29]
Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 2005; 52(2): 262-7.
[http://dx.doi.org/10.1016/j.jaad.2004.06.017] [PMID: 15692471]
[30]
Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 2011; 108(9): 1362-70.
[http://dx.doi.org/10.1016/j.amjcard.2011.06.054] [PMID: 21855836]
[31]
Suissa S, Bernatsky S, Hudson M. Antirheumatic drug use and the risk of acute myocardial infarction. Arthritis Rheum 2006; 55(4): 531-6.
[http://dx.doi.org/10.1002/art.22094] [PMID: 16874796]
[32]
Bernatsky S, Hudson M, Suissa S. Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis. Rheumatology (Oxford) 2005; 44(5): 677-80.
[http://dx.doi.org/10.1093/rheumatology/keh610] [PMID: 15784627]
[33]
Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum 2008; 38(2): 67-70.
[http://dx.doi.org/10.1016/j.semarthrit.2008.02.001] [PMID: 18395772]
[34]
Reiss AB, Carsons SE, Anwar K, et al. Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 2008; 58(12): 3675-83.
[http://dx.doi.org/10.1002/art.24040] [PMID: 19035488]
[35]
Ronda N, Greco D, Adorni MP, et al. Newly identified antiatherosclerotic activity of methotrexate and adalimumab: complementary effects on lipoprotein function and macrophage cholesterol metabolism. Arthritis Rheumatol 2015; 67(5): 1155-64.
[http://dx.doi.org/10.1002/art.39039] [PMID: 25605003]
[36]
Ridker PM, Everett BM, Pradhan A, et al. CIRT investigators. Low-Dose methotrexate for the prevention of atherosclerotic events. N Engl J Med 2019; 380(8): 752-62.
[http://dx.doi.org/10.1056/NEJMoa1809798] [PMID: 30415610]
[37]
Mangoni AA, Tommasi S, Zinellu A, et al. Repurposing existing drugs for cardiovascular risk management: a focus on methotrexate. Drugs Context 2018; 7212557
[http://dx.doi.org/10.7573/dic.212557] [PMID: 30459819]
[38]
Mangoni AA, Baghdadi LR, Shanahan EM, et al. Methotrexate, blood pressure and markers of arterial function in patients with rheumatoid arthritis: a repeated cross-sectional study. Ther Adv Musculoskelet Dis 2017; 9(9): 213-29.
[http://dx.doi.org/10.1177/1759720X17719850] [PMID: 28932292]
[39]
Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis 2006; 65(12): 1608-12.
[http://dx.doi.org/10.1136/ard.2005.050377] [PMID: 16793844]
[40]
Atzeni F, Turiel M, Caporali R, et al. The effect of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases. Autoimmun Rev 2010; 9(12): 835-9.
[http://dx.doi.org/10.1016/j.autrev.2010.07.018] [PMID: 20678592]
[41]
Widdifield J, Abrahamowicz M, Paterson JM, et al. Associations between methotrexate use and the risk of cardiovascular events in patients with elderly-onset rheumatoid arthritis. J Rheumatol 2019; 46(5): 467-74.
[http://dx.doi.org/10.3899/jrheum.180427] [PMID: 30504508]
[42]
Naranjo A, Sokka T, Descalzo MA, et al. QUEST-RA Group. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther 2008; 10(2): R30.
[http://dx.doi.org/10.1186/ar2383] [PMID: 18325087]
[43]
Tam HW, Yeo KJ, Leong PY, et al. Sulfasalazine might reduce risk of cardiovascular diseases in patients with ankylosing spondylitis: A nationwide population-based retrospective cohort study. Int J Rheum Dis 2017; 20(3): 363-70.
[http://dx.doi.org/10.1111/1756-185X.12986] [PMID: 27943609]
[44]
Gasparyan AY, Ayvazyan L, Cocco G, Kitas GD. Adverse cardiovascular effects of antirheumatic drugs: implications for clinical practice and research. Curr Pharm Des 2012; 18(11): 1543-55.
[http://dx.doi.org/10.2174/138161212799504759] [PMID: 22364138]
[45]
Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 1993; 23(2)(Suppl. 1): 82-91.
[http://dx.doi.org/10.1016/S0049-0172(10)80012-5] [PMID: 8278823]
[46]
Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ. Hydroxychloroquine directly reduces the binding of antiphospholipid an-tibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood 2008; 112(5): 1687-95.
[http://dx.doi.org/10.1182/blood-2008-03-144204] [PMID: 18577708]
[47]
Kerr G, Aujero M, Richards J, et al. Associations of hydroxychloroquine use with lipid profiles in rheumatoid arthritis: pharmacologic implications. Arthritis Care Res (Hoboken) 2014; 66(11): 1619-26.
[http://dx.doi.org/10.1002/acr.22341] [PMID: 24692402]
[48]
Lange Y, Duan H, Mazzone T. Cholesterol homeostasis is modulated by amphiphiles at transcriptional and post-transcriptional loci. J Lipid Res 1996; 37(3): 534-9.
[PMID: 8728316]
[49]
Schneider JG, Finck BN, Ren J, et al. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab 2006; 4(5): 377-89.
[http://dx.doi.org/10.1016/j.cmet.2006.10.002] [PMID: 17084711]
[50]
Munro R, Morrison E, McDonald AG, Hunter JA, Madhok R, Capell HA. Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis 1997; 56(6): 374-7.
[http://dx.doi.org/10.1136/ard.56.6.374] [PMID: 9227167]
[51]
Bili A, Sartorius JA, Kirchner HL, et al. Hydroxychloroquine use and decreased risk of diabetes in rheumatoid arthritis patients. J Clin Rheumatol 2011; 17(3): 115-20.
[http://dx.doi.org/10.1097/RHU.0b013e318214b6b5] [PMID: 21441823]
[52]
Wasko MC, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007; 298(2): 187-93.
[http://dx.doi.org/10.1001/jama.298.2.187] [PMID: 17622600]
[53]
Jung H, Bobba R, Su J, et al. The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus. Arthritis Rheum 2010; 62(3): 863-8.
[http://dx.doi.org/10.1002/art.27289] [PMID: 20131232]
[54]
Penn SK, Kao AH, Schott LL, et al. Hydroxychloroquine and glycemia in women with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 2010; 37(6): 1136-42.
[http://dx.doi.org/10.3899/jrheum.090994] [PMID: 20436082]
[55]
Rekedal LR, Massarotti E, Garg R, et al. Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases. Arthritis Rheum 2010; 62(12): 3569-73.
[http://dx.doi.org/10.1002/art.27703] [PMID: 20722019]
[56]
Gerstein HC, Thorpe KE, Taylor DW, Haynes RB. The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial. Diabetes Res Clin Pract 2002; 55(3): 209-19.
[http://dx.doi.org/10.1016/S0168-8227(01)00325-4] [PMID: 11850097]
[57]
Bevan AP, Christensen JR, Tikerpae J, Smith GD. Chloroquine augments the binding of insulin to its receptor. Biochem J 1995; 311(Pt 3): 787-95.
[http://dx.doi.org/10.1042/bj3110787] [PMID: 7487933]
[58]
Kalia S, Dutz JP. New concepts in antimalarial use and mode of action in dermatology. Dermatol Ther 2007; 20(4): 160-74.
[http://dx.doi.org/10.1111/j.1529-8019.2007.00131.x] [PMID: 17970883]
[59]
Sharma TS, Wasko MC, Tang X, et al. Hydroxychloroquine use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients. J Am Heart Assoc 2016; 5(1)e002867
[http://dx.doi.org/10.1161/JAHA.115.002867] [PMID: 26727968]
[60]
Li C, Wang XR, Ji HJ, et al. Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China. Clin Rheumatol 2017; 36(5): 1023-9.
[http://dx.doi.org/10.1007/s10067-017-3596-7] [PMID: 28342151]
[61]
Liu D, Li X, Zhang Y, et al. Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis. Drug Des Devel Ther 2018; 12: 1685-95.
[http://dx.doi.org/10.2147/DDDT.S166893] [PMID: 29928112]
[62]
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus er-ythematosus: a systematic review. Ann Rheum Dis 2010; 69(1): 20-8.
[http://dx.doi.org/10.1136/ard.2008.101766] [PMID: 19103632]
[63]
Costedoat-Chalumeau N, Hulot JS, Amoura Z, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardio-grams in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford) 2007; 46(5): 808-10.
[http://dx.doi.org/10.1093/rheumatology/kel402] [PMID: 17202178]
[64]
Cotroneo J, Sleik KM, Rene Rodriguez E, Klein AL. Hydroxychloroquine-induced restrictive cardiomyopathy. Eur J Echocardiogr 2007; 8(4): 247-51.
[http://dx.doi.org/10.1016/j.euje.2006.02.002] [PMID: 16600690]
[65]
Naqvi TZ, Luthringer D, Marchevsky A, Saouf R, Gul K, Buchbinder NA. Chloroquine-induced cardiomyopathy-echocardiographic features. J Am Soc Echocardiogr 2005; 18(4): 383-7.
[http://dx.doi.org/10.1016/j.echo.2004.09.029] [PMID: 15846170]
[66]
Hung YM, Lin L, Wang YH, Wei JC, Wang PY, Chiou JY. Combination effect of anti-rheumatic medications for coronary artery diseases risk in rheumatoid arthritis: a nationwide population-based cohort study. Curr Med Res Opin 2019; 35(2): 313-20.
[http://dx.doi.org/10.1080/03007995.2018.1492910] [PMID: 29939099]
[67]
Minoretti P, Bruno A, Di Vito C, Emanuele E. Leflunomide as an antiatherogenic drug. Med Hypotheses 2007; 68(5): 1175-6.
[http://dx.doi.org/10.1016/j.mehy.2006.10.036] [PMID: 17134845]
[68]
Nurmohamed MT, van Halm VP, Dijkmans BA. Cardiovascular risk profile of antirheumatic agents in patients with osteoarthritis and rheumatoid arthritis. Drugs 2002; 62(11): 1599-609.
[http://dx.doi.org/10.2165/00003495-200262110-00003] [PMID: 12109923]
[69]
Rozman B, Praprotnik S, Logar D, et al. Leflunomide and hypertension. Ann Rheum Dis 2002; 61(6): 567-9.
[http://dx.doi.org/10.1136/ard.61.6.567] [PMID: 12006342]
[70]
Yamaoka K. Tofacitinib for the treatment of rheumatoid arthritis: an update. Expert Rev Clin Immunol 2019; 15(6): 577-88.
[http://dx.doi.org/10.1080/1744666X.2019.1607298] [PMID: 30998415]
[71]
van Vollenhoven RF, Fleischmann R, Cohen S, et al. ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012; 367(6): 508-19.
[http://dx.doi.org/10.1056/NEJMoa1112072] [PMID: 22873531]
[72]
McInnes IB, Kim HY, Lee SH, et al. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis 2014; 73(1): 124-31.
[http://dx.doi.org/10.1136/annrheumdis-2012-202442] [PMID: 23482473]
[73]
Charles-Schoeman C, Wicker P, Sechtem U, et al. Cardiovascular safety findings in rheumatoid arthritis patients treated with tofacitinib (CP-690,550), a novel oral JAK inhibitor. Ann Rheum Dis 2012; 71: 201.
[74]
Charles-Schoeman C, Wicker P, Gonzalez-Gay MA, et al. Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor. Semin Arthritis Rheum 2016; 46(3): 261-71.
[http://dx.doi.org/10.1016/j.semarthrit.2016.05.014] [PMID: 27443588]
[75]
Gasparyan AY, Stavropoulos-Kalinoglou A, Mikhailidis DP, Douglas KM, Kitas GD. Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications. Rheumatol Int 2011; 31(2): 153-64.
[http://dx.doi.org/10.1007/s00296-010-1446-x] [PMID: 20390282]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy