Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study
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
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
Zdroje
1. WhalleyD
McKennaS
De JongZ
Van der HeijdeD
1997
Quality of life in rheumatoid arthritis.
Br J Rheumatol
25
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
36
182
188
3. JainM
RidkerP
2005
Anti-inflammatory effects of statins: clinical evidence and basic mechanisms.
Nat Rev Drug Discov
4
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
98
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
12
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
34
964
968
8. Van DoornumS
McCollG
WicksI
2004
Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis.
Ann Rheum Dis
63
1571
1575
9. HermannF
ForsterA
Chenevard
EnseleitF
HurlimannD
2005
Simvastatin improves endothelial function in patients with rheumatoid arthritis.
J Am Coll Cardiol
45
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
69
85
94
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
20
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
92
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
22
Suppl 3
13
23
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
18
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
25
2936
2957
21. MeyerJ
SchultzJ
O'DonnellJ
PatelP
SasaneR
2005
Patterns and effectiveness of lipid-lowering therapies in a managed care environment.
Value Health
8
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
81
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
75
1124
1132
24. ChengJWM
2004
Rosuvastatin in the management of hyperlipidemia.
Clin Ther
26
1368
1387
25. CoxDR
1972
Regression models and life tables (with discussion).
J R Stat Soc B
32
187
220
26. JickS
ChoiH
LiL
McInnesI
SattarN
2009
Hyperlipidaemia, statin use and the risk of developing rheumatoid arthritis.
Ann Rheum Dis
68
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
95
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
83
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
44
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
25
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
6
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
7
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
60
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
30
2167
2179
43. SunJ
GoochK
SvensonL
BellN
FrankC
2007
Estimating osteoarthritis incidence from population-based administrative health care databases.
Ann Epidemiol
17
51
56
44. EnglundM
JöudA
GeborekP
FelsonD
JacobssonL
2010
Prevalence and incidence of rheumatoid arthritis in southern Sweden 2008 and their relation to prescribed biologics.
Rheumatology
49
1563
1569
45. LazarevicM
ViticJ
MladenovicV
MyonesB
SkoseyJ
1992
Dyslipoproteinemia in the course of active rheumatoid arthritis.
Semin Arthritis Rheum
22
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
68
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
62
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
44
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
30
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
19
403
414
51. NicholsG
KoroC
2007
Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients.
Clin Ther
29
1761
1770
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2010 Číslo 9
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Pleiotropní účinky statinů na kardiovaskulární systém
- Statiny indukovaná myopatie: Jak na diferenciální diagnostiku?
- Zástava srdce u pacienta se střelnými ranami – kazuistika
- Statinová intolerance
Najčítanejšie v tomto čísle
- Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up?
- A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation
- Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study
- Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial