Влияние системного воспаления на эффект антиагрегантной терапии у больных с острым коронарным синдромом

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Abstract

Purpose. The aim of this study was to determine whether there is an association between antiplatelet therapy resistance and systemic inflammation in patients with acute coronary syndrome (ACS).

Methods. We included 122 patients with ACS hospitalized at Moscow City Hospital 23. We measured platelet function using simultaneous light transmittance aggregometry (spontaneous aggregation and ADP-induced), Thromboelastography Platelet Mapping (TEG-PM), Multiplate aggregometry and VerifyNow Aspirin and P2Y12 assays. The following markers of systemic inflammation were estimated: white blood cell count and plasma levels of high sensitivity C-reactive protein (hsCRP), soluble CD40-ligand (sCD40L), sP-selectin, von Willebrand factor, fibrinogen. All patients received aspirin at 250–325 mg and a loading dose of clopidogrel (300–600 mg) on arrival, followed by 125 mg of aspirin and 75 mg of clopidogrel per day. For the following analysis, the patients were separated into two groups. Both groups received atorvastatin: one group at 20 mg per day (n=18) and the second at 80 mg per day (n=24) for at least 7 days.

Results. We found that high white blood cell counts were associated with increased levels of 5 or 10 .M ADPinduced platelet aggregation and decreased percentages of P2Y12-inhibition (VerifyNow) (p=0.002, 0.004, and 0.017, respectively). High plasma levels of sP-selectin were associated with high levels of ADPtest (Multiplate) and decreased percentages of P2Y12-inhibition (VerifyNow) (p=0.046 and 0.047, respectively). Patients with elevated levels of plasma von Willebrand factor had increased 5 .M ADP-induced platelet aggregation (p=0,044). Kaplan–Meier survival analysis with a logrank significance test showed an association between a high risk of reinfarction during follow-up (1–22 months after ACS) and high levels both of 10 .M ADP-induced platelet aggregation and of HPR ADP (p=0.014 and 0.006, respectively). We found that this association remains significant among patients with high levels of hs-CRP (p=0.021), while in the group of patients with low levels of hs-CRP this relationship was not significant. Among patients receiving atorvastatin at 20 mg, the association between a high risk of reinfarction and high levels of platelet aggregation also remained significant (p=0.003). In contrast, among patients receiving atorvastatin at 80 mg, this association disappeared.

Conclusions. High on-treatment platelet reactivity is associated with several laboratory signs of systemic inflammation and predicts a poor prognosis in patients with ACS. High-dose statin therapy can overcome the association between high on-treatment platelet reactivity and poor prognosis in patients with ACS.

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Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery