Aggregometric assessment of clonidine's impact on the efficacy of dual platelet inhibition.

BACKGROUND: Clonidine is commonly used as a calmative and antihypertensive agent in perioperative care. Due to the drug's alpha-2-agonistic effects, it has recently been hypothesised that clonidine may affect platelet aggregability. The present investigation aimed to study the potential impact of clonidine on the efficacy of dual antiplatelet therapy. METHODS: In this prospective, observational, single-centre study, patients treated with dual antiplatelet therapy were screened for eligibility. The patients were enrolled in the study if ex vivo thrombin-induced (TRAPtest), arachidonic acid-induced (ASPItest) and adenosine diphosphate-induced (ADPtest) platelet aggregation, as measured using multiple electrode aggregometry (MEA; Multiplate, Roche AG, Grenzach, Germany), confirmed efficient dual platelet inhibition. Ex vivo induced platelet aggregation was assessed before (baseline) and 3 minutes after (T1) spiking blood samples with either 1 ng/mL clonidine or sodium chloride 0.9% (control group). RESULTS: In total, 34 patients were finally enrolled in the study. Compared with baseline, platelet aggregation in the ASPItest and ADPtest was significantly increased at T1 in both groups. Platelet aggregation in the TRAPtest remained unchanged between baseline and T1 in both groups. Comparing platelet aggregation at T1, we detected no differences between blood samples that were spiked with clonidine and blood samples that were spiked with sodium chloride 0.9% in the TRAPtest, the ASPItest, or the ADPtest. CONCLUSIONS: The results of this study indicate that clonidine does not affect platelet aggregability in patients treated with dual antiplatelet therapy. The findings of the study also indicate that ex vivo induced platelet aggregation in the ASPItest and ADPtest increases with the duration between blood drawing and MEA analyses.

Response to dual antiplatelet therapy in patients with peripheral artery occlusive disease suffering from critical limb ischemia.

BACKGROUND: Failure to reach the level of therapeutic anticoagulation represents a risk factor for occlusive events in patients suffering from peripheral arterial disease. Our study aimed to analyze the prevalence of nonresponse to dual antiplatelet therapy in a group of patients admitted to our hospital with critical limb ischemia (CLI) following stent-thrombosis. METHODS: This prospective study was approved by the local Ethics Review Board. Patients with critical limb ischemia following stent thrombosis were included if dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel per day had been administered over three months prior to enrollment. The antiaggregatory effects were analyzed using the Multiple Electrode Aggregometry (MEA, Multiplate®, Roche AG, Grenzach, Germany). The primary endpoints were the area under the aggregation curve (AUC) of the ex-vivo-induced platelet aggregation following stimulation with adenosine diphosphate (ADP, ADPtest) and arachidonic acid (ASPItest). RESULTS: Sixty patients were enrolled in this study. Platelet aggregation was 39.6 (24/54) [median (25th/75th percentile)] U in the ADPtest and 22.4 (13/35) U in the ASPItest. Effective aspirin- and ADP-induced therapeutic inhibition of platelet aggregation was confirmed in 78% and 53% of our patients, respectively. Effective dual platelet inhibition was achieved in 27 patients (45%). A non-response to both of the antiaggregatory drugs was found in 14% of the patients. CONCLUSIONS: The results of the present study indicate a high prevalence of nonresponse to antiaggregatory medication in our study collective. Further studies are needed to confirm our hypothesis that individual adjustments of both aspirin and clopidogrel dosages may potentially reduce the incidence of CLI in patients suffering from peripheral arterial occlusive disease.