Interaction between the LMWH reviparin and aspirin in healthy volunteers

Abstract

Aims: To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1-5).

Methods: In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 microg ml-1) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT).

Results: Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of Amax; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modified if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xa-activity and heptest compared with reviparin alone.

Conclusions: We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical significance.

Figure 1

Template bleeding times (min) prior to drug application at day 1 and 5. (a). ASA alone 300 mg once daily from day 1–5, (b). Reviparin 6300 anti-Xa-units once daily. from day 3–5 and (c). ASA 300 mg once daily.and reviparin 6300 anti-Xa-units once daily from day 3–5. Star indicates same subject.

Figure 2

(a) Anti-Xa-activity (U ml⁻¹) after repeated doses of reviparin (6300 anti-Xa-units once daily from day 3–5) with (▴) or without (□) concomitant application of ASA (300 mg once daily from day 1–5). (b) Heptest (s) after repeated doses of reviparin (6300 anti-Xa-units once daily from day 3–5) with (▴) or without (□) concomitant application of ASA (300 mg once daily from day 1–5).