The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review

Rheumatology (Oxford). 2010 Feb;49(2):295-307. doi: 10.1093/rheumatology/kep366. Epub 2009 Nov 27.


Objectives: Patients with RA have an increased prevalence of cardiovascular disease (CVD). This is due to traditional risk factors and the effects of chronic inflammation. MTX is the first-choice DMARD in RA. We performed a systematic literature review to determine whether MTX affects the risk of CVD in patients with RA.

Methods: We searched Medline, Embase, Cochrane database, database of abstracts of reviews of effects, health technology assessment and Science Citation Index from 1980 to 2008. Conference proceedings (British Society of Rheumatology, ACR and EULAR) were searched from 2005 to 2008. Papers were included if they assessed the relationship between MTX use and CVD in patients with RA. Two reviewers independently assessed each title and abstract for relevance and quality.

Results: A total of 2420 abstracts were identified, of which 18 fulfilled the inclusion criteria. Two studies assessed the relationship between MTX use and CVD mortality, one demonstrated a significant reduction in CVD mortality and the second a trend towards reduction. Five studies considered all-cause CVD morbidity. Four demonstrated a significant reduction in CVD morbidity and the fifth a trend towards reduction. MTX use in the year prior to the development of RA decreased the risk of CVD for 3-4 years. Four studies considered myocardial infarction, one demonstrated a decreased risk and three a trend towards decreased risk with MTX use.

Conclusion: The current evidence suggests that MTX use is associated with a reduced risk of CVD events in patients with RA. This suggests that reducing the inflammation in RA using MTX not only improves disease-specific outcomes but may also reduce collateral damage such as atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Insulin Resistance / physiology
  • Lipids / blood
  • Methotrexate / therapeutic use*


  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Lipids
  • Methotrexate