Download PDF
CC BY 4.0 · TH Open 2020; 04(03): e236-e244
DOI: 10.1055/s-0040-1716734
Original Article

Different Types of Statins and All-Cause Mortality during Anticoagulation for Venous Thromboembolism: Validation Study from RIETE Registry

Carmine Siniscalchi 
1   Department of Internal and Emergency Medicine, Angiology Unit, Parma University Hospital, Parma, Italy
,
José M. Suriñach
2   Department of Internal Medicine, Hospital Universitario Vall d'Hebron, Barcelona, Spain
,
Adriana Visonà
3   Department of Vascular Medicine, Ospedale Castelfranco Veneto, Castelfranco Veneto, Italy
,
José L. Fernández-Reyes
4   Department of Internal Medicine, Complejo Hospitalario de Jaén, Jaén, Spain
,
Covadonga Gómez-Cuervo 
5   Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
,
Peter Verhamme
6   Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium
,
Pablo J. Marchena
7   Department of Internal Medicine and Emergency, Parc Sanitari Sant Joan de Déu-Hospital General, Barcelona, Spain
,
Dominique Farge-Bancel
8   Department of Internal Medicine and Pathology, Hôpital Saint-Louis, Paris, France
,
Jorge Moisés 
9   Department of Pneumonology, Hospital Universitario Clínic de Barcelona, Barcelona, Spain
,
Manuel Monreal
10   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Universidad Católica de Murcia, Spain
,
and the RIETE Investigators › Author Affiliations Funding We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant.
› Further Information
   Permissions and Reprints

Abstract

Introduction We previously reported that during the course of anticoagulation for venous thromboembolism (VTE) patients using statins were at a lower risk to die than nonusers.

Methods We used the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry to validate our previous findings in a subsequent cohort of patients and to compare the risk of death according to the use of different types of statins.

Results From January 2018 to December 2019, 19,557 patients with VTE were recruited in RIETE. Of them, 4,065 (21%) were using statins (simvastatin, 1,406; atorvastatin, 1,328; rosuvastatin, 246; and others, 1,085). During anticoagulation (192 vs.182 days, for statin and no statin users respectively), 500 patients developed a VTE recurrence, 519 suffered major bleeding, and 1,632 died (fatal pulmonary embolism [PE], 88 and fatal bleeding, 78). On multivariable analysis, statin users were at a lower risk to die (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.59–0.79) than nonusers. When separately analyzing the drugs, on multivariable analysis, patients using simvastatin (HR = 0.64; 95% CI: 0.52–0.80), atorvastatin (HR 0.72; 95% CI: 0.58–0.89), or other statins (HR = 0.67; 95% CI: 0.52–0.87) were at a lower risk to die than nonusers. For those using rosuvastatin, difference was not statistically significant (HR = 0.77; 95% CI: 0.50–1.19), maybe due to the sample size.

Conclusion Our data validate previous findings and confirm that VTE patients using statins at baseline are at a lower risk to die than nonusers. No statistically differences were found according to type of statins.

Keywords

atorvastatin - simvastatin - rosuvastatin - venous thromboembolism - death

Note

Coordinator of the RIETE Registry: M.M.


RIETE steering committee members: Paolo Prandoni, Benjamin Brenner, and D.F.-B.


RIETE national coordinators: Raquel Barba (Spain), Pierpaolo Di Micco (Italy), Laurent Bertoletti (France), Sebastian Schellong (Germany), Inna Tzoran (Israel), Abilio Reis (Portugal), Marijan Bosevski (R. Macedonia), Henri Bounameaux (Switzerland), Radovan Malý (Czech Republic), Peter Verhamme (Belgium), Joseph A. Caprini (USA), and Hanh My Bui (Vietnam).


RIETE Registry coordinating center: S&H Medical Science Service.


* A complete list of RIETE investigators is given in the [Supplementary Material].


Supplementary Material



Publication History

Received: 23 March 2020

Accepted: 11 August 2020

Article published online:
17 September 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Hong KS, Lee JS. Statins in acute ischemic stroke: a systematic review. J Stroke 2015; 17 (03) 282-301
    CrossrefPubMedGoogle Scholar
  • 2 Ní Chróinín D, Asplund K, Åsberg S. et al Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials. Stroke 2013; 44 (02) 448-456
    CrossrefPubMedGoogle Scholar
  • 3 Szummer K, Lundman P, Jacobson SH. et al Association between statin treatment and outcome in relation to renal function in survivors of myocardial infarction. Kidney Int 2011; 79 (09) 997-1004
    CrossrefPubMedGoogle Scholar
  • 4 Tonelli M, Moyé L, Sacks FM, Kiberd B, Curhan G. Cholesterol and Recurrent Events (CARE) Trial Investigators. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med 2003; 138 (02) 98-104
    CrossrefPubMedGoogle Scholar
  • 5 Zhang X, Jing J, Zhao X. et al Statin use during hospitalization and short-term mortality in acute ischaemic stroke with chronic kidney disease. Eur Neurol 2018; 79 (5,6): 296-302
    CrossrefPubMedGoogle Scholar
  • 6 Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res 2017; 120 (01) 229-243
    CrossrefPubMedGoogle Scholar
  • 7 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) 1851-1861
    CrossrefPubMedGoogle Scholar
  • 8 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: 223-231
    CrossrefPubMedGoogle Scholar
  • 9 Orsi FA, Biedermann JS, Kruip MJHA. et al Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial. J Thromb Haemost 2019; 17 (02) 319-328
    CrossrefPubMedGoogle Scholar
  • 10 Biere-Rafi S, Hutten BA, Squizzato A. et al Statin treatment and the risk of recurrent pulmonary embolism. Eur Heart J 2013; 34 (24) 1800-1806
    CrossrefPubMedGoogle Scholar
  • 11 Schmidt M, Cannegieter SC, Johannesdottir SA, Dekkers OM, Horváth-Puhó E, Sørensen HT. Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case-control study. J Thromb Haemost 2014; 12 (08) 1207-1215
    CrossrefPubMedGoogle Scholar
  • 12 Siniscalchi C, Quintavalla R, Rocci A. , et al; RIETE Investigators. Statin and all-cause mortality in patients receiving anticoagulant therapy for venous thromboembolism. Data from the RIETE registry. Eur J Intern Med 2019; 68: 30-35
    CrossrefPubMedGoogle Scholar
  • 13 Muriel A, Jiménez D, Aujesky D. , et al; RIETE Investigators. Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk. J Am Coll Cardiol 2014; 63 (16) 1675-1683
    CrossrefPubMedGoogle Scholar
  • 14 Farge D, Trujillo-Santos J, Debourdeau P. , et al; RIETE Investigators. Fatal events in cancer patients receiving anticoagulant therapy for venous thromboembolism. Medicine (Baltimore) 2015; 94 (32) e1235
    CrossrefPubMedGoogle Scholar
  • 15 Jiménez D, de Miguel-Díez J, Guijarro R. , et al; RIETE Investigators. Trends in the management and outcomes of acute pulmonary embolism. Analysis from the RIETE Registry. J Am Coll Cardiol 2016; 67 (02) 162-170
    CrossrefPubMedGoogle Scholar
  • 16 Muñoz-Torrero JFS, Bounameaux H, Pedrajas JM. , et al; Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Investigators. Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis. J Vasc Surg 2011; 54 (6, suppl) 26S-32S
    CrossrefPubMedGoogle Scholar
  • 17 Moustafa F, Pesavento R, di Micco P. , et al; RIETE Investigators. Real-life use of anticoagulants in venous thromboembolism with a focus on patients with exclusion criteria for direct oral anticoagulants. Clin Pharmacol Ther 2018; 103 (04) 684-691
    CrossrefPubMedGoogle Scholar
  • 18 Monreal M, Kakkar AK, Caprini JA. , et al; RIETE Investigators. The outcome after treatment of venous thromboembolism is different in surgical and acutely ill medical patients. Findings from the RIETE registry. J Thromb Haemost 2004; 2 (11) 1892-1898
    CrossrefPubMedGoogle Scholar
  • 19 Bikdeli B, Jimenez D, Hawkins M. , et al; RIETE Investigators. Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 2018; 118 (01) 214-224
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Stone NJ, Robinson JG, Lichtenstein AH. , et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63 (25 pt B): 2889-2934
    CrossrefPubMedGoogle Scholar
  • 21 Biedermann JS, Kruip MJHA, van der Meer FJ. et al Rosuvastatin use improves measures of coagulation in patients with venous thrombosis. Eur Heart J 2018; 39 (19) 1740-1747
    CrossrefPubMedGoogle Scholar
  • 22 Tripodi A, Legnani C, Chantarangkul V, Cosmi B, Palareti G, Mannucci PM. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008; 6 (08) 1327-1333
    CrossrefPubMedGoogle Scholar
  • 23 Szczeklik A, Musiał J, Undas A. et al Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia. J Am Coll Cardiol 1999; 33 (05) 1286-1293
    CrossrefPubMedGoogle Scholar
  • 24 Cortellaro M, Cofrancesco E, Arbustini E. et al Atorvastatin and thrombogenicity of the carotid atherosclerotic plaque: the ATROCAP study. Thromb Haemost 2002; 88 (01) 41-47
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Macchia A, Laffaye N, Comignani PD. et al Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial. PLoS One 2012; 7 (03) e32894
    CrossrefPubMedGoogle Scholar
  • 26 Ural AU, Yilmaz MI, Avcu F, Yalcin A. Treatment with cerivastatin in primary mixed hyperlipidemia induces changes in platelet aggregation and coagulation system components. Int J Hematol 2002; 76 (03) 279-283
    CrossrefPubMedGoogle Scholar
  • 27 Ridker PM, Danielson E, Fonseca FA. , et al; JUPITER Trial Study Group. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373 (9670): 1175-1182
    CrossrefPubMedGoogle Scholar
  • 28 Kessinger CW, Kim JW, Henke PK. et al Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring. PLoS One 2015; 10 (02) e0116621
    CrossrefPubMedGoogle Scholar