A new multi-hospital 4,000 patient study of the benefit of statin therapy for rheumatoid arthritis has begun enrolling in the UK in a national five-year trial.
The trial is jointly funded by the Arthritis Research Campaign and the British Heart Foundation, and is the largest academically led trial to ever be conducted in rheumatoid arthritis patients in the world. I stress that this is an academically funded and led trial, not drug company.
Eight years ago in my first book on statins, "Lipitor, Thief of Memory" I reported that the special anti-inflammatory effect of statins ultimately would result in its use for any disease with a significant inflammatory component, specifically mentioning rheumatoid arthritis.
Ora Shovman first described "the anti-inflammatory and immunomodulatory aspects of statins" in 2001. This was a remarkable observation and one which apparently had not yet been observed by the developers of the statin class of drugs, despite anti-inflammation appearing to be the primary mechanism whereby statins reduce cardiovascular risk.
Longitudinal studies brought this out when cardiovascular benefit was observed despite minimal or no cholesterol reduction.
This observation was a hard sell at first because cholesterol causation was so firmly established. After 40 years of anti-cholesterol brainwashing few doctors could willingly accept the existence of an alternative explanation. As the research evidence gradually corroborated this new reality we realized the irrelevance of cholesterol reduction to cardiovascular disease.
Throughout this time period we had been using cholesterol reduction as a marker of proper dosing of the new statin drugs when cholesterol was not the underlying cause.
Cholesterol we were learning was critical not only to cognitive function and personality but also cell identification and cell communication.
In addition to being a primary constituent of our cell walls, cholesterol is necessary also for the formation and function of the so-called lipid rafts for cell communication, the process of, exocytosis and endocytosis vital for cell metabolism and even functions as insulation necessary for nerve function. Everywhere we look, cholesterol is there, playing a vital role. The cause of heart disease and strokes....never!
Doctors running the trial say that most patients with rheumatoid arthritis should be put on a statin drug as a matter of course anyhow, as if trying to justify the decision to use statins.
Used for its anti-inflammatory effect their decision to use statins has merit. Used in this manner the dosage should be at anti-inflammatory levels only, recognizing that cholesterol reduction is irrelevant. Used in this manner the mevalonate pathway is not likely to be blocked and the risk of disabling side effects will be minimal.
People with rheumatoid arthritis have long been known to have an increased risk of dying from cardiovascular disease. After all, they are chronically ill, usually have been for decades, during which time they are intensively treated with powerful medications such as gold, methotrexate and the highest tolerable doses of anti-inflammatory agents such as prostaglandins and Cox 2 inhibitors. This alone may well account for increased cardiovascular risk.
I have little doubt that the use of statins for their powerful anti-inflammatory effect will prove beneficial just as it would be in other autoimmune and organ transplant cases as long as the mevalonate pathway is not compromised by excessively high doses.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor