Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study

English version České info

Background:
The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA.

Methods and Findings:
The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins.

A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52–0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81–0.88) compared to nonadherent patients.

Conclusions:
The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.

: Please see later in the article for the Editors' Summary

Vyšlo v časopise: Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study. PLoS Med 7(9): e32767. doi:10.1371/journal.pmed.1000336
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000336

Souhrn

Zdroje

1. WhalleyD

McKennaS

De JongZ

Van der HeijdeD

1997

Quality of life in rheumatoid arthritis.

Br J Rheumatol

773

777

2. AlamanosY

VoulgariP

DrososA

2006

Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review.

Semin Arthritis Rheum

182

188

3. JainM

RidkerP

2005

Anti-inflammatory effects of statins: clinical evidence and basic mechanisms.

Nat Rev Drug Discov

977

987

4. RidkerP

BuringJ

ShihJ

MatiasM

HennekensC

1998

Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.

Circulation

731

733

5. Abud-MendozaC

de la FuenteH

Cuevas-OrtaE

BarandaL

Cruz-RizoJ

2003

Therapy with statins in patients with refractory rheumatic diseases: a preliminary study.

Lupus

607

611

6. McCareyD

McInnesI

MadhokR

HampsonR

ScherbakovO

2004

Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.

Lancet

363

2015

2021

7. OkamotoH

KoizumiK

KamitsujiS

InoueE

HaraM

2007

Beneficial action of statins in patients with rheumatoid arthritis in a large observational cohort.

J Rheumatol

964

968

8. Van DoornumS

McCollG

WicksI

2004

Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis.

Ann Rheum Dis

1571

1575

9. HermannF

ForsterA

Chenevard

EnseleitF

HurlimannD

2005

Simvastatin improves endothelial function in patients with rheumatoid arthritis.

J Am Coll Cardiol

461

464

10. LodiS

EvansS

EggerP

CarpenterJ

2010

Is there an anti-inflammatory effect of statins in rheumatoid arthritis? Analysis of a large routinely collected claims database.

Br J Clin Pharmacol

11. ShalevV

ChodickG

SilberH

KokiaE

JanJ

2009

Continuation of statin treatment and all-cause mortality: a population-based cohort study.

Arch Intern Med

169

260

268

12. ChodickG

HeymannA

FlashS

KokiaE

ShalevV

2010

Persistence with statins and incident cataract: a population-based historical cohort study.

Ann Epidemiol

136

142

13. BendelacJ

2009

Membership in sick funds 2008

Jerusalem

Israel National Insurance Institute

14. Li Wan PoA

1998

Dictionary of evidence-based medicine

Oxford

Radcliffe Medical Press

15. KopjarB

SalesA

PinerosS

SunH

LiY

2003

Adherence with statin therapy in secondary prevention of coronary heart disease in veterans administration male population.

Am J Cardiol

1106

1108

16. AvornJ

MonetteJ

LacourA

BohnR

MonaneM

1998

Persistence of use of lipid-lowering medications: a cross-national study.

JAMA

279

1458

1462

17. BennerJ

TierceJ

BallantyneC

PrasadC

BullanoM

2004

Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy.

Pharmacoeconomics

Suppl 3

18. Israel Central Bureau of Statistics

1998

1995 census of population and housing

Jerusalem

Israel Central Bureau of Statistics

19. ChodickG

HeymannAD

ShalevV

KookiaE

2003

The epidemiology of diabetes in a large Israeli HMO.

Eur J Epidemiol

1143

1146

20. ValuckR

WilliamsS

MacArthurM

SaseenJ

NairK

2003

A retrospective cohort study of correlates of response to pharmacologic therapy for hyperlipidemia in members of a managed care organization.

Clin Ther

2936

2957

21. MeyerJ

SchultzJ

O'DonnellJ

PatelP

SasaneR

2005

Patterns and effectiveness of lipid-lowering therapies in a managed care environment.

Value Health

601

612

22. JonesP

KafonekS

LauroraI

HunninghakeD

1998

Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study).

Am J Cardiol

582

587

23. DujovneC

KnoppR

KwiterovichP

HunninghakeD

McBrideT

2000

Randomized comparison of the efficacy and safety of cerivastatin and pravastatin in 1030 hypercholesterolemic patients; the Cerivastatin Study Group.

May Clin Proc

1124

1132

24. ChengJWM

2004

Rosuvastatin in the management of hyperlipidemia.

Clin Ther

1368

1387

25. CoxDR

1972

Regression models and life tables (with discussion).

J R Stat Soc B

187

220

26. JickS

ChoiH

LiL

McInnesI

SattarN

2009

Hyperlipidaemia, statin use and the risk of developing rheumatoid arthritis.

Ann Rheum Dis

546

551

27. EndresM

LaufsU

HuangZ

NakamuraT

HuangP

1998

Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase.

Proc Natl Acad Sci U S A

8880

8885

28. EssigM

NguyenG

PrieD

EscoubetB

SraerJ

1998

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells: role of geranylgeranylation and Rho proteins.

Circ Res

683

690

29. del RincónI

WilliamsK

SternM

FreemanG

EscalanteA

2001

High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors.

Arthritis Rheum

2737

2745

30. ArnaudC

BurgerF

SteffensS

VeillardNR

NguyenTHT

2005

Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins.

Arterioscler Thromb Vasc Biol

1231

1236

31. KobashigawaJA

KatznelsonS

LaksHJJ

YeatmanL

WangXM

1995

Effect of pravastatin on outcomes after cardiac transplantation.

N Engl J Med

333

621

627

32. KwakB

MulhauptF

MyitS

MachF

2000

Statins as a newly recognized type of immunomodulator.

Nat Med

1399

1402

33. Weitz-SchmidtG

WelzenbachK

BrinkmannV

KamataT

KallenJ

2001

Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.

Nat Med

687

692

34. ShimadaK

MiyauchiK

DaidaH

2004

Early intervention with atorvastatin modulates TH1/TH2 imbalance in patients with acute coronary syndrome: from bedside to bench.

Circulation

109

e213

e214

35. RidkerP

DanielsonE

FonsecaF

GenestJ

GottoAJ

2008

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

N Engl J Med

359

2195

2207

36. RayK

SeshasaiS

ErqouS

SeverP

JukemaJ

2010

Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants.

Arch Intern Med

170

1024

1031

37. RidkerP

SolomonD

2009

Should patients with rheumatoid arthritis receive statin therapy?

Arthritis Rheum

1205

1209

38. LaupacisA

MamdaniM

2004

Observational studies of treatment effectiveness: some cautions.

Ann Intern Med

140

923

924

39. Hippisley-CoxJ

CouplandC

2010

Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.

BMJ

340

C1297

40. GrangerB

SwedbergK

EkmanI

GrangerC

OlofssonB

2005

Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial.

Lancet

366

2005

2011

41. DormuthC

PatrickA

ShrankW

WrightJ

GlynnR

2009

Statin adherence and risk of accidents: a cautionary tale.

Circulation

119

2051

2057

42. ChodickG

ShalevV

GerberY

HeymannA

SilberH

2008

Long-term persistence with statin treatment in a not-for-profit health maintenance organization: a population-based retrospective cohort study in Israel.

Clin Ther

2167

2179

43. SunJ

GoochK

SvensonL

BellN

FrankC

2007

Estimating osteoarthritis incidence from population-based administrative health care databases.

Ann Epidemiol

44. EnglundM

JöudA

GeborekP

FelsonD

JacobssonL

2010

Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics.

Rheumatology

1563

1569

45. LazarevicM

ViticJ

MladenovicV

MyonesB

SkoseyJ

1992

Dyslipoproteinemia in the course of active rheumatoid arthritis.

Semin Arthritis Rheum

172

178

46. ChoyE

SattarN

2009

Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions.

Ann Rheum Dis

460

469

47. BoersM

NurmohamedM

DoelmanC

LardL

VerhoevenA

2003

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.

Ann Rheum Dis

842

845

48. Hurt-CamejoE

ParedesS

MasanaL

CamejoG

SartipyP

2001

Elevated levels of small, low density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis. Possible contribution of phospholipase A2 to this atherogenic profile.

Arthritis Rheum

2761

2767

49. ChodickG

ShalevV

GerberY

HeymannA

SilberH

2008

Long-term persistence with statin treatment in a not-for-profit health maintenance organization: a population-based retrospective cohort study in Israel.

Clin Ther

2167

2179

50. BruckertE

HayemG

DejagerS

YauC

Be'gaudB

2005

Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients-the PRIMO study.

Cardiovasc Drugs Ther

403