약물용출 스텐트 삽입 후 추가적 Cilostazol 투여의 임상적 효과 = Clinical Effects of Additional Cilostazol Administration After Drug-Eluting Stent Insertion

국문 초록 (Abstract)

배경 및 목적: Cilostazol은 선택적 PDE III 억제제로서 혈소판내의 cAMP 수준을 증가시키며 항혈소판응집 작용뿐만 아니라 혈관확장효과도 가지고 있다. 이에 본 연구진은 약물용출 스텐트 삽입 후 2자요법 치료를 받고 있는 환자에서 추가적 cilostazol 투여 시 임상효과를 전향적으로 조사하고자 하였다.
방 법: 2003년 12월부터 2006년 6월까지 동아대학교 의료원에서 성공적으로 약물용출 스텐트를 삽입한 603명의 환자를선출하여 2자요법 치료군 (PCI 시술 후 aspirin 과 clopidogrel을6개월 이상 복용, n=301)과 3자요법 치료군 (PCI 시술 후 aspirin과 clopidogrel을 6개월 이상 복용, cilostazol 는 1개월 투여, n=302)으로 나누어서 1개월, 6개월 MACE 을 추적 관찰하였다. MACE의 정의는 사망, MI, stent thrombosis, TLR을 포함한 것으로 하였다. 총 66명의 환자에서 (2자요법군 n=40, 3자요법군 n=26) Chrono-Log platelet aggregometer와 VerifyNow P2Y12 assay 시스템을이용하여 혈소판기능을 평가하였다.
결 과: PCI 시술 후 1개월 MACE rate는 3자요법군에서 0.66% (사망 0.66%), 2자요법군에서 1.67% (사망 0.67%, MI 0.67%, stent thrombosis 0.99%, TLR 0.99%)으로서 두 군 사이에서 통계학적으로 의미 있는 차이를 보이지 않았다 (p=0.087).
6개월 추적결과에서 두 군 사이에서도 MACE rate가 의미있는 차이를 보여주지 않았다 (3자요법군 vs. 2자요법군= 2.65% vs. 3.99%, p=0.864). 혈소판 응집능에 관한 실험실검사소견에서 ADP (27.92±13.04% vs. 40.9±15.78%, p= 0.0008), collagen (13.73±6.95% vs. 27.43±14.87%, p= 0.03) 그리고 epinephrine (10.38±7.82% vs. 15.5±10.45%, p=0.0000) 에 대한 응집능은 3자요법군에서 통계학적으로의미 있게 감소하였으나 arachidonic acid (3.23±1.07% vs. 3.78±2.12%, p=0.23)과 restocetin (29.19±35.55% vs. 44.78±32.65%, p=0.07)에 대한 응집능뿐만 아니라 VerifyNow로측정한 aspirin reaction unit (412.96±96.25 vs. 427.93±76.24, p=0.48)도 두 군 사이에서 의미 있는 차이를 보이지 않았다.
Dong Sung Kum, et al.·25 결 론: 약물용출 스텐트 삽입 후 추가적 cilostazol의 투여는 기존의 2자요법과 비교할 때 6개월 MACE rate을 유의하게감소시키지 못하였다.

다국어 초록 (Multilingual Abstract)

Background and Objectives: Cilostazol, a selective inhibitor of phosphodiesterase III (PDE III), prevents inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP) and irreversibly inhibits platelet aggregation and vasodilation. Hence, we performed this prospective randomized study to evaluate the clinical effects of additional cilostazol administration in patients receiving dual antiplatelet therapy after drugeluting stent (DES) insertion.
Subjects and Methods: Between December 2003 and June 2006, we enrolled a total 603 consecutive patients who underwent successful percutaneous coronary intervention (PCI) with DES insertion at Dong-A University Hospital. Study patients received dual antiplatelet therapy (aspirin and clopidogrel, n=301) for at least six months or dual antiplatelet therapy (six months) combined with cilostazol medication for one month (triple therapy, n=302) after PCI. We investigated the incidence of major adverse cardiac events (MACE) at one month and six months after the initiation of medical therapy. MACE was defined as a composite of death, myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). Platelet function was evaluated in 66 patients (dual therapy group, n=40; triple therapy group, n=26) using a Chrono-Log platelet aggregometer and the VerifyNow P2Y12 assay system.
Results: The MACE rate was 0.66% in the triple therapy group (death only, 0.67%) and 1.67% in the dual therapy group (death, 0.67%; MI, 0.67%; stent thrombosis, 0.99%; TLR, 0.99%) at one month after PCI (p=0.087). At six months, there were no differences in the MACE rate between the two groups (triple group vs. dual group=2.65% vs. 3.99%, p=0.864). In laboratory tests, platelet aggregation induced by agonists of ADP (27.92±13.04% vs. 40.9±15.78%, p=0.0008), collagen (13.73±6.95% vs. 27.43±14.87%, p=0.03), and epinephrine (10.38±7.82% vs. 15.5±10.45%, p=0.0000) were lower in the triple therapy group versus the dual therapy group. However, platelet aggregation induced by agonists of arachidonic acid (3.23±1.07% vs. 3.78±2.12%, p=0.23) and ristocetin (29.19±35.55% vs. 44.78±32.65%, p= 0.07) and aspirin reaction unit (412.96±96.25 vs. 427.93±76.24, p=0.48) measured by VerifyNow were not different in the triple group versus the dual group.
Conclusion: Additional administration of cilostazol did not decrease the MACE rate when compared to dual therapy six months after PCI in patients with DES.

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