VANCOUVER, B.C. – Count arthritis among the possible side effects of clopidogrel, according to investigators from the Westchester Medical Center in Valhalla, N.Y.
The number of reported cases – 11 – is vanishingly small compared with the number of people who have used the drug. In 2012 alone, 11.3 million prescriptions were written for the branded product Plavix in the United States, according to IMS Health, a health care information company.
Dr. Sahil Agrawal
Still, it’s something to keep in mind if a patient suddenly develops stiff, swollen joints shortly after starting the drug, exactly what happened to a 64-year-old man at the medical center following a 300-mg loading dose and a few days of 75-mg maintenance therapy after stent placement.
"He had been on the maintenance dose for 3 days when he first started to have a fever, and then he started to have joint symptoms" about 2 weeks after the procedure, said Dr. Sahil Agrawal, an internal medicine resident and lead investigator. The fever persisted, and did not respond to antibiotics.
The man presented with a stiff neck, painful right shoulder, and markedly limited range of motion in both joints; the next day he developed painful swelling, redness, and a restricted range of motion in both hands and wrists. His erythrocyte sedimentation rate and C-reactive protein levels were both elevated, but findings from uric acid concentration and other tests were normal. Radiographs of the affected joints showed only degenerative changes; a few white cells were aspirated from his shoulder joint. He was negative for Lyme disease, brucellosis, and familial Mediterranean fever.
"We did an extensive differential diagnosis and ruled out everything under the sun. At the same time, we learned that he had [similar] symptoms with" a single loading dose of Plavix a year earlier, "so we went back into the literature. Once we had an idea that this was possible, we stopped his clopidogrel and switched him to prasugrel. Within the next few days, his symptoms went away and have not come back," Dr. Agrawal said at the 18th World Congress on Heart Disease.
The timing of the man’s symptoms and their quick resolution when the drug was stopped "strongly suggest clopidogrel-associated arthritis. [Previous authors have] advised careful use of clopidogrel in patients with a history of arthritis. We recommend considering clopidogrel as a cause of acute arthritis," and avoiding using it again "in patients with a prior unexplained episode of arthritis temporally related to clopidogrel therapy," Dr. Agrawal and his colleagues concluded in their recently published case report and literature review (J. Investig. Med. 2013 Aug. 5 [doi:10.1177/2324709613500239]).
All but 1 of the previous 10 reported cases were in men. Joint symptoms started after 2-3 weeks of maintenance therapy, except in one case when they started after 3 days. Both small and large joints were affected, usually more than one. Synovitis was the hallmark exam finding.
Erythrocyte sedimentation rate and C-reactive protein levels were elevated in all cases; fever, itching, and maculopapular rashes were also common. The pattern "suggests a possible immunologic basis for these symptoms," the investigators noted.
In every case, the symptoms went away shortly after clopidogrel was stopped.
Dr. Agrawal and his colleagues reported having no relevant financial disclosures.