Careless talk may cost lives in attributing adverse events to ADP receptor antagonists

Editor—Dakik et al in their article suggest an association between the prescription of an ADP receptor antagonist (ticlodipine) with the onset of acute arthritis.¹ We would like to express a note of caution. This article follows a previous one discussing another ADP receptor antagonist (clopidogrel) and the development of acute arthritis.² These drugs are increasingly used in combination with aspirin for the prevention of thrombosis after coronary artery stenting and have been shown to be safe and efficacious.³,⁴ It is therefore important that adverse events that lead to the withdrawal of treatment are correctly attributable to the drug and not just the coincidental occurrence of another common condition.

Many commonly prescribed drugs have reportedly been associated with the onset of connective tissue disease, but the complaint is usually arthralgia rather than a true inflammatory synovitis.⁵ We agree that the clinical picture of the latest case associated with an urticarial rash suggests that an idiosyncratic drug reaction is more likely. But without rechallenging patients and documenting a further reaction, an association remains only inferred and not proved.

Patients with acute coronary syndromes or undergoing coronary stenting often have multiple risk factors for acute gout or pseuodogout. They are almost universally prescribed aspirin, often coprescribed diuretics, and usually from an age group at risk of crystal arthritis. We recently admitted a patient whose case history shows the need for caution before these drugs develop a potentially erroneous reputation.

A 62 year old man awaiting assessment for coronary artery bypass grafting was admitted with unstable angina. He started treatment with clopidogrel, and 72 hours later he developed an acutely painful, swollen right elbow. Awareness of the recent case report raised a possible link between the drug and the arthritis. We aspirated the elbow with difficulty, however, and this confirmed gout. His symptoms resolved over the next few days, the clopidogrel was continued, and the acute coronary syndrome settled.

If we had been unsuccessful in obtaining synovial fluid, the timing of the onset of arthritis after starting treatment with clopidogrel and its reported association might have falsely convinced us that stopping the drug was the best course of action. This would have denied our patient the optimal treatment for his angina and may also have precluded the use of ADP antagonists after any surgical intervention. We wish to reaffirm our concern that the start of an inflammatory arthritis is not prematurely attributed to these ADP antagonists without further objective evidence including rechallenging of possible cases.