Dipyrone – a pain killer which may ‘kill’ aspirin's antiplatelet action

Aims: Acetylsalicylic acid (Aspirin®) is routinely used after CABG as antiplatelet agent. Since the pyrazole analgesic dipyrone (Novalgin®) is often co-administered with aspirin and also known to interact with cyclooxygenase, the target of aspirin, we hypothesized that a drug interaction between aspirin and novalgin may contribute to aspirin resistance.

Methods: The antiplatelet effect of aspirin (100µM) was investigated in platelet rich plasma (PRP) from patients before and after CABG by arachidonic acid (1 mmol/l) – induced aggregation and thromboxane formation. All patients received aspirin orally, starting day 1 after CABG. To determine the impact of dipyrone on the antiplatelet effect of aspirin in vitro (30µM), measurements were also performed with PRP from healthy volunteers in presence of the active dipyrone metabolite 4-methylaminoantipyrine (MAA, 3µM).

Results: Inhibitory effect of aspirin in vitro is given in the following table:

(* indicates p<0.05 vs. control).
	aggregation		thromboxane-formation
	before surgery	after surgery	before surgery	after surgery
CABG patients (day 5, n=15)	19.5±4.4%*	79.6±17.7%	15.5±5%*	75.6±17.1%
	no MAA	MAA (3µM)	no MAA	MAA (3µM)
Volunteers (n=12)	0%*	58.3±14.7%	5.6±3.2%*	57.9±17.9%

Conclusion: The results indicate that the antiplatelet effect of aspirin is partially blunted after CABG, as well as in presence of MAA, the active metabolite of dipyrone. Since dipyrone is widely used for analgesic treatment after cardiac surgery, it should be used with caution in patients with cardiovascular disease depending on a efficient antiplatelet therapy.