Van Solingen R M, Rosenstein E D, Mihailescu G, Drejka M L, Kalia A, Cohen A J, Kramer N
Department of Medicine, Saint Barnabas Medical Center, 200 South Orange Avenue, Livingston, NJ 07039, USA.
Am J Med. 2001 Sep;111(4):285-9. doi: 10.1016/s0002-9343(01)00838-5.
Although aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exert inhibitory effects on platelets in vitro and in vivo, there are insufficient data to substantiate the use of NSAIDs alone as antiplatelet drugs in patients already taking aspirin. We therefore sought to determine whether aspirin, added to NSAID therapy, further suppresses platelet function.
We enrolled 25 healthy adult volunteers who were administered ketoprofen (extended-release capsules, 200 mg daily) for 1 week, followed by ketoprofen (200 mg daily) and aspirin (325 mg daily) or ketoprofen (200 mg daily) alone during the second week. Platelet aggregation, stimulated by epinephrine and arachidonic acid, and cyclooxygenase activity, measured by thromboxane B(2), were measured at baseline, on day 8, and on day 15.
On day 8, all subjects demonstrated abnormal platelet aggregation (>50% inhibition), which persisted at day 15 in both the aspirin and no aspirin groups. One week of ketoprofen treatment reduced thromboxane B(2) levels by 84% in the aspirin group and by 85% in the no aspirin group (P = 0.8), without any further inhibition measured on day 15.
Extended-release ketoprofen significantly inhibited platelet aggregation and thromboxane B(2) production in healthy volunteers. Addition of aspirin had no additional effect. Trials are warranted to determine whether these in vitro effects result in clinical antiplatelet activity in patients who require chronic treatment with NSAIDs, thereby avoiding the toxicity of NSAID/aspirin combination therapy.
尽管阿司匹林和其他非甾体抗炎药（NSAIDs）在体外和体内对血小板均有抑制作用，但尚无足够数据证实已服用阿司匹林的患者单独使用NSAIDs作为抗血小板药物的有效性。因此，我们试图确定在NSAIDs治疗基础上加用阿司匹林是否能进一步抑制血小板功能。
我们招募了25名健康成年志愿者，先给予酮洛芬（缓释胶囊，每日200mg）治疗1周，然后在第二周给予酮洛芬（每日200mg）加阿司匹林（每日325mg）或单独给予酮洛芬（每日200mg）。在基线、第8天和第15天测量由肾上腺素和花生四烯酸刺激的血小板聚集以及通过血栓素B2测量的环氧化酶活性。
在第8天，所有受试者均表现出异常的血小板聚集（抑制率>50%），在第15天，阿司匹林组和未用阿司匹林组均持续存在。酮洛芬治疗1周后，阿司匹林组血栓素B2水平降低84%，未用阿司匹林组降低85%（P = 0.8），在第15天未测得进一步抑制作用。
缓释酮洛芬可显著抑制健康志愿者的血小板聚集和血栓素B2生成。加用阿司匹林无额外作用。有必要进行试验以确定这些体外效应是否能在需要长期NSAIDs治疗的患者中产生临床抗血小板活性，从而避免NSAIDs/阿司匹林联合治疗的毒性。
