Kardiovaskulaarisairauksien riski nivelreuman kortisonihoidossa

Kari Puolakka

Näytön aste: C

Kortisonihoito saattaa annoksesta riippuen lisätä sydän- ja verisuonisairauksien riskiä nivelreumapotilailla.

In a population-based cohort study «Aviña-Zubieta JA, Abrahamowicz M, De Vera MA ym. I...»1 8384 incident RA cases (1997–2006, a total of 50 238 person-years) with GC use experienced 298 incident MI events ascertained using hospitalization and vital statistics data. Current GC use was associated with 68 % increased risk of MI (Hazard ratio, HR = 1.68; 95 % CI 1.14–2.47). Similarly, current daily dose (HR = 1.14; 95 % CI 1.05–1.24 per each 5 mg/day increase), cumulative duration of use (HR = 1.14, 95 % CI 1.00–1.29 per year of GC use) and total cumulative dose (HR = 1.06; 95 % CI 1.02–1.10 per gram accumulated in the past) were also associated with increased risk of MI. Furthermore, current dose and cumulative use were independently associated with an increased risk of MI (10 % per additional year on GCs and 13 % per 5 mg/day increase).

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

In a retrospective study «Mazzantini M, Talarico R, Doveri M ym. Incident co...»2 by review of medical records the prevalence of comorbidity in a cohort of 365 patients with rheumatoid arthritis (RA), treated (n = 297, 81.3 %) or not (n = 68, 18.7 %) with low-dose glucocorticoids (GC, 4–6 mg methylprednisolone daily) and who have been followed for at least 10 years.

Fragility fractures occurred in 18.2 % of GC users and in 6.0 % of GC nonusers (p < 0.02); arterial hypertension in 32.3 % of GC users and in 10.4 % of GC nonusers (p < 0.0005); acute myocardial infarction in 13.1 % of GC users and in 1.5 % of the nonusers (p < 0.01). Prevalence of diabetes mellitus, cataract, and infections was comparable. We divided GC users into groups of different duration of GC therapy: < 2, 2–5, and > 5 years; the mean duration of GC treatment was 1.3 + 0.5, 3.6 + 1.1, and 12.1 + 5.1 years, respectively. GC treatment for > 5 years was associated with significantly higher prevalence of fragility fractures (26.6 %; p < 0.001 vs the other groups), arterial hypertension (36.7 %; p < 0.0002 vs nonusers and GC users < 2 years), myocardial infarction (16.1 %; p < 0.01 vs nonusers), and infections (9.7 %; p < 0.005 vs the other groups). GC treatment for 2–5 years was associated with a significantly higher prevalence of arterial hypertension (30.0 %; p < 0.01) compared to nonusers.

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: hyvä

A systematic literature review «Roubille C, Richer V, Starnino T ym. The effects o...»3was performed to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso.

Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Nested in BARFOT Study «Ajeganova S, Svensson B, Hafström I ym. Low-dose p...»4, 223 patients with early RA were included in a 2-year open randomised trial comparing prednisolone 7.5 mg/day in addition to disease-modifying antirheumatic drugs (DMARDs) with DMARD therapy alone. Participants

were followed for 10 years since inclusion into the original prednisolone trial or until occurrence of the studied outcomes. Setting: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations.

The participants had no history of CV events at baseline and incident cases were identified via the Swedish Hospital Discharge and Cause of Death Registries.

Outcomes: Composite CV events, that is, ischaemic coronary and cerebrovascular events, components of the composite CV outcome, and death.

Results: Within 2041 person-years, 17 incident composite CV events occurred in 112 patients (15%) randomised to prednisolone, and 15 events of 111 patients (14%) who were assigned not to receive prednisolone. There were nine deaths (8%) in each group.

There was no difference in the age-adjusted relative hazards (HRs; 95% CI) for the first composite CV event, first coronary event and death in the prednisolone group versus the group not treated with prednisolone were 1.8 (0.9 to 3.6), 0.98 (0.4 to 2.6) and 1.6 (0.6 to 4.1), respectively.

The risk for the first cerebrovascular event showed a 3.7-fold increased relative hazard (95% CI1.2 to 11.4) among prednisolone treated patients.

  • Tutkimuksen laatu: tasokas
  • Sovellettavuus suomalaiseen väestöön: hyvä

Kommentti: Satunnaistettu, kontrolloitu tutkimusasetelma. Valtaosa prednisolonille allokoiduista potilaista lopetti lääkkeen seurannan aikana. Aivovaltimotapahtumien määrä oli vähäinen ja tulos on altis virhelähteille.

In an observation study «del Rincón I, Battafarano DF, Restrepo JF ym. Gluc...»5 779 RA patients from rheumatology clinics were followed up for a total of 7,203 person-years. The glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status were assessed. During the follow-up 237 patients died, yielding a mortality rate of 3.2 per 100 person-years (95% confidence interval [95% CI] 2.8-3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5-2.1). Exposure to glucocorticoids was associated with a dose-dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05-1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all-cause mortality was 8-15 mg, with an adjusted HR of 1.78 (95% CI 1.22-2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all-cause mortality was 40 gm (HR 1.74 [95% CI 1.25-2.44]).

  • Tutkimuksen laatu: kelvollinen
  • Sovellettavuus suomalaiseen väestöön: kohtalainen

A literature review of recent RCTs on the safety of glucocorticoid (GC) treatment RA was performed «Santiago T, da Silva JA. Safety of low- to medium-...»6. The authors conclude that low- to medium-dose glucocorticoid regimens have continued to be evaluated in randomized clinical trials, particularly in early disease, but these studies also have relevant methodological limitations in assessing safety, particularly due to small size and/or short duration. At present, there is no evidence that low-dose GCs are associated with significant toxicity in early RA over 2 years besides weight gain and probably glaucoma. The evidence on which to support clear recommendations about glucocorticoid toxicity remains remarkably weak.

Kommentti: Katsaus tukee käsitystä matala-annoksisen lyhytkestoisen glukokortikoidihoidon turvallisuudesta.


Glukokortikoidien käyttöön näyttää isoissa seuranta-aineistoissa liittyvän sydän- ja verisuonitapahtumien lisääntymistä, mikä voi johtua siitä, että glukokortikoidien käyttäjiksi valikoituu niitä potilaita, joiden tulehdusta ei saada kuriin varsinaisin reumalääkkein «Boers M. Drugs and cardiovascular risk in inflamma...»7.


  1. Aviña-Zubieta JA, Abrahamowicz M, De Vera MA ym. Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocardial infarction in rheumatoid arthritis: a population-based study. Rheumatology (Oxford) 2013;52:68-75 «PMID: 23192907»PubMed
  2. Mazzantini M, Talarico R, Doveri M ym. Incident comorbidity among patients with rheumatoid arthritis treated or not with low-dose glucocorticoids: a retrospective study. J Rheumatol 2010;37:2232-6 «PMID: 20843913»PubMed
  3. Roubille C, Richer V, Starnino T ym. 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;74:480-9 «PMID: 25561362»PubMed
  4. Ajeganova S, Svensson B, Hafström I ym. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ Open 2014;4:e004259 «PMID: 24710131»PubMed
  5. del Rincón I, Battafarano DF, Restrepo JF ym. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol 2014;66:264-72 «PMID: 24504798»PubMed
  6. Santiago T, da Silva JA. Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years. Ann N Y Acad Sci 2014;1318:41-9 «PMID: 24814757»PubMed
  7. Boers M. Drugs and cardiovascular risk in inflammatory arthritis: another case of glucocorticoid-bashing? Ann Rheum Dis 2015;: «PMID: 25714930»PubMed