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Platelet function during long-term treatment with ketanserin of claudicating patients with peripheral
Insights
Ketanserin treatment in patients with peripheral atherosclerosis reduced platelet aggregation and serotonin content. This study confirms ketanserin
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Peripheral atherosclerosis is associated with increased platelet reactivity and activation.
- Claudicating patients exhibit heightened platelet response to serotonin and signs of in vivo platelet activation.
- Platelet dysfunction contributes to the pathophysiology of peripheral atherosclerosis.
Purpose of the Study:
- To investigate the long-term effects of ketanserin on platelet function in patients with peripheral atherosclerosis.
- To compare the efficacy of ketanserin with placebo in modulating platelet activity.
- To assess specific markers of platelet aggregation, serotonin content, and release factors.
Main Methods:
- A multi-center, double-blind, placebo-controlled trial was conducted.
- 173 claudicating patients received either ketanserin (63 patients) or placebo (84 patients) for 1 year.
- Platelet aggregation, platelet serotonin content, plasma beta-thromboglobulin (beta TG), platelet factor 4 (PF4), and serum thromboxane B2 (TXB2) were analyzed.
Main Results:
- Ketanserin significantly reduced 5-hydroxytryptamine (5-HT)-induced platelet aggregation and platelet 5-HT content.
- Plasma PF4 and beta TG levels increased from pre-medication values in both ketanserin and placebo groups.
- A subgroup with elevated baseline beta TG showed reduced levels after ketanserin treatment, suggesting a specific effect.
Conclusions:
- Ketanserin demonstrates significant effects on specific platelet functions, including reduced aggregation and serotonin content, in patients with peripheral atherosclerosis.
- Long-term ketanserin administration may modulate platelet activity in this patient population.
- Further research is warranted to elucidate the clinical implications of these findings.
Abstract:
In a multi-center, double-blind, placebo-controlled trial in claudicating patients with peripheral atherosclerosis, the effects of 1 year of treatment with ketanserin (20 mg t.i.d. for 1 month, 40 mg t.i.d. thereafter; n = 63 patients) or placebo (n = 84 patients) on platelet function (aggregation in P.R.P. by 5-HT 5 x 10(-6) M, ADP 1 to 5 x 10(-6) M, collagen 2 micrograms/ml; platelet 5-HT content; plasma beta TG- and PF4-levels; serum TXB2) were analyzed. Before treatment, claudicating patients (n = 173) displayed an higher reactivity of platelets to 5-HT and signs of platelet activation/release in vivo (higher plasma beta TG-PF4, lower platelet 5-HT content and decreased platelet aggregation by ADP, collagen) in comparison with healthy controls (n = 50). After 1 year of treatment with ketanserin, but not with placebo, platelet aggregation induced by 5-HT (slope -41.1%) and platelet 5-HT content (-23.7%) were significantly reduced. PF4 and beta TG were significantly higher than their pre-medication values in the two trial groups. The other platelet function tests were not significantly modified by the treatment. Only the small subgroup of patients with initially elevated plasma beta TG levels (greater than 20 ng/ml) also scrutinized for hidden NSAID consumption or technical bias (exclusion of data with serum TXB2 less than or equal to 10000 pg/100 microliters and/or plasma PF4 greater than 10 ng/ml) had significantly lower plasma beta TG levels (-22.7%) than the pre-medication values after treatment with ketanserin, but not with placebo. The present study confirms that ketanserin affects some platelet functions, during long-term administration in claudicating patients with atherosclerosis.