Statins and Venous Thromboembolic Disease – Where are we Now?

Page: [297 - 300] Pages: 4

  • * (Excluding Mailing and Handling)

Abstract

Classical risk factors for atherosclerosis also play a role in the pathogenesis of venous thromboembolism (VTE). Low-density lipoprotein cholesterol has prothrombotic and endothelium- deteriorating effects which are not limited to the arterial system. The association between hypercholesterolemia and VTE has been established, but the benefits of statins in the prevention of VTE assessed by observation studies seemed equivocal. The large, randomized trial Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) recorded the occurrence of VTE as a protocol-specified endpoint and reported a reduced incidence of VTE among subjects taking 20 mg of rosuvastatin daily vs placebo (hazard ratio 0.57; 95% confidence interval 0.37-0.86; p=0.007). Similar results were confirmed by meta-analyses of observation studies and randomized trials. Recently, a Mendelian randomization study that took the presence of gene variants coding for less efficient hydroxymethyl-glutaryl coenzyme A reductase activity as a proxy for statin treatment, confirmed a small, but significant negative association between the score of selected genetic polymorphisms and the incidence of VTE. However, since the protective effects of statins are limited, they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment.

[1]
Bagot CN, Arya R. Virchow and his triad: A question of attribution. Br J Haematol 2008; 143(2): 180-90.
[http://dx.doi.org/10.1111/j.1365-2141.2008.07323.x] [PMID: 18783400]
[2]
Goldhaber SZ. Venous thromboembolism prophylaxis: Quality, location (hospital vs. home), and duration. Thromb Haemost 2009; 102(7): 01-2.
[http://dx.doi.org/10.1160/TH09-05-0292] [PMID: 19572058]
[3]
Piazza G. Beyond virchow’s triad: Does cardiovascular inflammation explain the recurrent nature of venous thromboembolism? Vasc Med 2015; 20(2): 102-4.
[http://dx.doi.org/10.1177/1358863X14568706] [PMID: 25832597]
[4]
Prandoni P, Bilora F, Marchiori A, et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003; 348(15): 1435-41.
[http://dx.doi.org/10.1056/NEJMoa022157] [PMID: 12686699]
[5]
Poredos P, Jezovnik MK. Dyslipidemia, statins, and venous thromboembolism. Semin Thromb Hemost 2011; 37(8): 897-902.
[http://dx.doi.org/10.1055/s-0031-1297368] [PMID: 22198854]
[6]
Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: A meta-analysis. Circulation 2008; 117(1): 93-102.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.709204] [PMID: 18086925]
[7]
Anand SS. Smoking. Circulation 2017; 135(1): 17-20.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025024] [PMID: 28028060]
[8]
Kawasaki T, Kambayashi J, Ariyoshi H, Sakon M, Suehisa E, Monden M. Hypercholesterolemia as a risk factor for deep-vein thrombosis. Thromb Res 1997; 88(1): 67-73.
[http://dx.doi.org/10.1016/S0049-3848(97)00192-8] [PMID: 9336875]
[9]
Ferroni P, Basili S, Davi G. Platelet activation, inflammatory mediators and hypercholesterolemia. Curr Vasc Pharmacol 2003; 1(2): 157-69.
[http://dx.doi.org/10.2174/1570161033476772] [PMID: 15320841]
[10]
Wang N, Tall AR. Cholesterol in platelet biogenesis and activation. Blood 2016; 127(16): 1949-53.
[http://dx.doi.org/10.1182/blood-2016-01-631259] [PMID: 26929273]
[11]
Higashi Y. Endothelial function in dyslipidemia: Roles of LDL-cholesterol, HDL-cholesterol and triglycerides. Cells 2023; 12(9): 1293.
[http://dx.doi.org/10.3390/cells12091293] [PMID: 37174693]
[12]
Poredos P, Jezovnik MK. Endothelial dysfunction and venous thrombosis. Angiology 2018; 69(7): 564-7.
[http://dx.doi.org/10.1177/0003319717732238] [PMID: 28954526]
[13]
Sofi F, Marcucci R, Abbate R, Gensini GF, Prisco D. Lipoprotein (a) and venous thromboembolism in adults: A meta-analysis. Am J Med 2007; 120(8): 728-33.
[http://dx.doi.org/10.1016/j.amjmed.2007.01.029] [PMID: 17679133]
[14]
Vaseghi G, Ghahdarijani HK, Taheri M, et al. Hematological inflammatory markers in patients with clinically confirmed familial hypercholesterolemia. BioMed Res Int 2022; 2022: 1-6.
[http://dx.doi.org/10.1155/2022/5051434] [PMID: 35083330]
[15]
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41(1): 111-88.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[16]
Herrington DM, Vittinghoff E, Lin F, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation 2002; 105(25): 2962-7.
[http://dx.doi.org/10.1161/01.CIR.0000019406.74017.B2] [PMID: 12081988]
[17]
Davis JW, Weller SC, Porterfield L, Chen L, Wilkinson GS. Statin use and the risk of venous thromboembolism in women taking hormone therapy. JAMA Netw Open 2023; 6(12): e2348213.
[http://dx.doi.org/10.1001/jamanetworkopen.2023.48213] [PMID: 38100102]
[18]
Zaccardi F, Kunutsor SK, Seidu S, Davies MJ, Khunti K. Is the lower risk of venous thromboembolism with statins related to low-density-lipoprotein reduction? A network meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis 2018; 271: 223-31.
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.02.035] [PMID: 29524865]
[19]
Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360(18): 1851-61.
[http://dx.doi.org/10.1056/NEJMoa0900241] [PMID: 19329822]
[20]
Agarwal V, Phung OJ, Tongbram V, Bhardwaj A, Coleman CI. Statin use and the prevention of venous thromboembolism: A meta-analysis. Int J Clin Pract 2010; 64(10): 1375-83.
[http://dx.doi.org/10.1111/j.1742-1241.2010.02439.x] [PMID: 20716146]
[21]
Li R, Yuan M, Yu S, et al. Effect of statins on the risk of recurrent venous thromboembolism: A systematic review and meta-analysis. Pharmacol Res 2021; 165: 105413.
[http://dx.doi.org/10.1016/j.phrs.2020.105413] [PMID: 33412275]
[22]
Rodriguez AL, Wojcik BM, Wrobleski SK, Myers DD Jr, Wakefield TW, Diaz JA. Statins, inflammation and deep vein thrombosis: A systematic review. J Thromb Thrombolysis 2012; 33(4): 371-82.
[http://dx.doi.org/10.1007/s11239-012-0687-9] [PMID: 22278047]
[23]
Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S. Effect of statins on a wide range of health outcomes: A cohort study validated by comparison with randomized trials. Br J Clin Pharmacol 2009; 67(1): 99-109.
[http://dx.doi.org/10.1111/j.1365-2125.2008.03308.x] [PMID: 19006546]
[24]
Doggen CJM, Lemaitre RN, Smith NL, Heckbert SR, Psaty BM. HMG CoA reductase inhibitors and the risk of venous thrombosis among postmenopausal women. J Thromb Haemost 2004; 2(5): 700-1.
[http://dx.doi.org/10.1111/j.1538-7836.2004.00696.x] [PMID: 15099273]
[25]
Yang CC, Jick SS, Jick H. Statins and the risk of idiopathic venous thromboembolism. Br J Clin Pharmacol 2002; 53(1): 101-5.
[http://dx.doi.org/10.1046/j.0306-5251.2001.01523.x] [PMID: 11849201]
[26]
Wells PS, Gebel M, Prins MH, Davidson BL, Lensing AWA. Influence of statin use on the incidence of recurrent venous thromboembolism and major bleeding in patients receiving rivaroxaban or standard anticoagulant therapy. Thromb J 2014; 12(1): 26.
[http://dx.doi.org/10.1186/1477-9560-12-26] [PMID: 25698905]
[27]
Delluc A, Tromeur C, Le Moigne E, et al. Lipid lowering drugs and the risk of recurrent venous thromboembolism. Thromb Res 2012; 130(6): 859-63.
[http://dx.doi.org/10.1016/j.thromres.2012.08.296] [PMID: 22939687]
[28]
Brækkan SK, Deelder CC, Siegerink B, et al. Statin use and risk of recurrent venous thrombosis: Results from the MEGA follow‐up study. Res Pract Thromb Haemost 2017; 1(1): 112-9.
[http://dx.doi.org/10.1002/rth2.12003] [PMID: 30046679]
[29]
Siniscalchi C, Quintavalla R, Rocci A, et al. Statin and all-cause mortality in patients receiving anticoagulant therapy for venous thromboembolism. Data from the RIETE registry. Eur J Intern Med 2019; 68: 30-5.
[http://dx.doi.org/10.1016/j.ejim.2019.07.028] [PMID: 31427187]
[30]
Albertsen IE, Søgaard M, Goldhaber SZ, et al. Development of sex-stratified prediction models for recurrent venous thromboembolism: A danish nationwide cohort study. Thromb Haemost 2020; 120(5): 805-14.
[http://dx.doi.org/10.1055/s-0040-1708877] [PMID: 32369851]
[31]
Marston NA, Gurmu Y, Melloni GEM, et al. The effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of venous thromboembolism. Circulation 2020; 141(20): 1600-7.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046397] [PMID: 32223429]
[32]
Wallace A, Albadawi H, Hoang P, et al. Statins as a preventative therapy for venous thromboembolism. Cardiovasc Diagn Ther 2017; 7(S3): S207-18.
[http://dx.doi.org/10.21037/cdt.2017.09.12] [PMID: 29399524]
[33]
Arslan F, Pasterkamp G, de Kleijn DP. Unraveling pleiotropic effects of statins: Bit by bit, a slow case with perspective. Circ Res 2008; 103(4): 334-6.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.182220] [PMID: 18703784]
[34]
Sen-Banerjee S, Mir S, Lin Z, et al. Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation 2005; 112(5): 720-6.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.525774] [PMID: 16043642]
[35]
Kunutsor SK, Seidu S, Khunti K. Statins and primary prevention of venous thromboembolism: A systematic review and meta-analysis. Lancet Haematol 2017; 4(2): e83-93.
[http://dx.doi.org/10.1016/S2352-3026(16)30184-3] [PMID: 28089655]
[36]
Liu G, Shi M, Mosley JD, et al. A mendelian randomization approach using 3-HMG-Coenzyme-A reductase gene variation to evaluate the association of statin-induced low-density lipoprotein cholesterol lowering with noncardiovascular disease phenotypes. JAMA Netw Open 2021; 4(6): e2112820.
[http://dx.doi.org/10.1001/jamanetworkopen.2021.12820] [PMID: 34097045]
[37]
Ma XS, Sun J, Geng R, et al. Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study. Nutr Metab Cardiovasc Dis 2023; 33(5): 1087-92.
[http://dx.doi.org/10.1016/j.numecd.2023.02.023] [PMID: 36958971]
[38]
Li L, Zhang P, Tian JH, Yang K. Statins for primary prevention of venous thromboembolism. Cochrane Libr 2014; (12): CD008203.
[http://dx.doi.org/10.1002/14651858.CD008203.pub3] [PMID: 25518837]
[39]
Langenecker KS, Eriksen FC, Thienpont E, Barauskas G. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35(2): 116-22.
[http://dx.doi.org/10.1097/EJA.0000000000000705] [PMID: 28901992]
[40]
Mukherjee D, Nissen SE. Lipoprotein (a) as a biomarker for cardiovascular diseases and potential new therapies to mitigate risk. Curr Vasc Pharmacol 2023; 22
[http://dx.doi.org/10.2174/0115701611267835231210054909] [PMID: 38141196]