Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Sulfasalazine and Its Metabolites Inhibit Platelet Function in Patients with Inflammatory Arthritis.
MacMullan1, Paul A., Madigan1, Anne M., Paul2, Nevin, Peace2, Aaron J., Bagaglia1, Paola M., Alagha2, Ahmed, Nolan2, Kevin B.
Patients with inflammarory arthritis (IA) are at increased risk of adverse cardiovascular events. Sulfasalazine therapy has been shown to decrease this risk, independent of disease severity. Previous evidence suggests that sulfasalazine inhibits platelet thromboxane synthetase, but its effecs on platelet function are unknown.Therefore, we decided to assess the effect of sulfasalazine and its metabolites on platelet function in patients with IA.
135 consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or NSAIDs were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other DMARDs and no sulfasalazine. Platelet function in response to multiple agonists was tested, and these 2 cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfsalazine and its metabolites on arachidonic acid (AA) induced platelet aggregation was also tested in vitro, in samples from healthy donors (n=18).
Demographics, CVD risk factors, and disease activity indices were similar in the Sulfasalazine and Other DMARDs groups. AA-induced platelet aggregation was significantly inhibited in the Sulfasalazine group (9±7%) and comparable to that in the Aspirin group (10±6%), (see Figure). In contrast, there was no effect on AA-induced platelet aggregation in the Other DMARDs group (77±12%), (p<0.001). Sulfasalazine therapy had no effect on platelet function in response to the other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced aggregation in vitro (p<0.001).
Figure. Platelet aggregation in response to arachidonic acid is significantly inhibited in both the Sulfasalazine and Aspirin group compared to those on Other DMARDs. *** p<0.001.
The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin, and is dependent on both sulfasalazine and its metabolites. This is a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.
To cite this abstract, please use the following information:
MacMullan, Paul A., Madigan, Anne M., Paul, Nevin, Peace, Aaron J., Bagaglia, Paola M., Alagha, Ahmed, et al; Sulfasalazine and Its Metabolites Inhibit Platelet Function in Patients with Inflammatory Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :447