Category Archives: methotrexate

Rheumatoid arthritis drugs… which ones are friendly to the heart and which ones aren’t!

Rheumatoid arthritis (RA) is a chronic, autoimmune systemic disease which affects approximately two million Americans. While the symptoms that bring the patient to the doctor are the joint swelling and pain, the area of most concern may not be the joints.  It is well established that cardiovascular risk is markedly increased in RA and in fact it is this complication that shortens lifespan by between ten to fifteen years.

A number of clinical studies have retrospectively examined the relationship between certain medications and the risk of cardiovascular events.  The report card has provided some real surprises.heart-attack_0

For example, methotrexate, the workhorse disease modifying anti-rheumatic drug (DMARD) of choice reduces cardiovascular mortality by almost 70 per cent. The mechanism is felt to be due to a reduction of atherosclerotic plaque formation as well as increased clearance of foam cells (Solomon DH, et al. Circulation 2003; 11: 1303-1307).

The other major player in the treatment of RA is the TNF inhibitor group.  These are used in more than 50 per cent of RA patients in the US. These drugs apparently reduce the risk of cardiovascular events by almost 50 per cent (Gonzalaz A, et al. Ann Rheum Dis. 2008; 67: 64-69). Why this occurs is still not clearly understood.

Steroids have been used to treat RA since the early 1950’s.  Steroids have been shown to worsen cardiovascular risk because of their effects on both blood pressure as well as blood glucose.  Steroid use in RA has been associated with increased carotid plaque formation as well as increased arterial stiffness.  So what dose is a safe dose?  The answer is still unknown.

Non-steroidal anti-inflammatory drugs (NSAIDS) raise blood pressure.  Randomized clinical trials have shown that cardiovascular risk is associated with COX-2 inhibitors but also with non-selective COX drugs also.  The upshot? All NSAIDS regardless of class, are associated with increased cardiovascular risk.

Hydroxychloroquine, a drug often used to treat mild RA, is associated with a decrease in diabetes and may also improve lipid status.  Actemra increases lipid profile but the long term effects are still unknown.  Leflunomide (Arava) increases blood pressure.  The eventual effects are still a subject of conjecture.

So what about aspirin?  This medication is used for cardiovascular prophylaxis.  In higher doses it also has anti-inflammatory effects although these are limited by the potential gastrointestinal side effects known to be caused by high dose aspirin. It is well known that other NSAIDS should not be used in patients taking aspirin for cardiovascular prophylaxis since they blunt that effect.

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