個別に調整した薬物投与によりPCI後の有害事象が軽減
する（LBCT, abstract # 1313）

個別に合わせた用量のクロピドグレルをPCI後に投与することによりステント血栓発現率が有意に減少する

Individually tailored doses of clopidogrel following PCI significantly reduced rate of stent thrombosis

個別に合わせた用量のクロピドグレル投与は非緊急のステント留置を伴う経皮的冠動脈インターベンション（PCI）後の有害事象発現率を低下させる、と2008年American Heart Association学会で発表された。ステント血栓予防のための血小板機能モニタリングに基づくクロピドグレル導入用量の調整（Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Stent Thrombosis）のスタディの結果である。研究者らは429人の「低反応者」（薬物に対する反応の低下した患者）を調査した。うち214人はコントロール群で通常の600mgのクロピドグレルを投与された。テスト群はVASPリン酸化解析におけるスコアをカットオフレベルに低下させることを目標として、最大3倍多い用量のクロピドグレルを24時間ごとに投与された。クロピドグレルを増量し最大計2,400mgのクロピドグレルを内服したにもかかわらず、低反応者のうち8%は依然として低反応であった。しかし、用量を個別に合わせることにより、出血イベントを有意に増やすことなく一次および二次エンドポイントイベントが有意に減少した。早期の明らかなステント血栓は個別調整用量患者で0.5%に対しコントロール群では4.2%であった（p<0.01）。MACE率は個別治療群で実質的に低かった（0.5%対コントロール群8.9%）。出血発現率は両群間で差がなかった。

Individually tailored doses of clopidogrel significantly cut the rate of adverse events after non-emergent percutaneous coronary intervention (PCI) with stenting, researchers reported at the American Heart Association's Scientific Sessions 2008. Results of the Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Stent Thrombosis study were presented as a late-breaking clinical trial.

Clopidogrel reduces blood platelets' tendency to clot in response to injury, such as the stretching of the blood vessels during PCI. However, individuals respond differently to the drug, with a significant number deemed "low responders," those having a reduced response to the drug.

That led to the hypothesis that an individualized approach might magnify the benefits of clopidogrel, said Franck Paganelli, M.D., Ph.D., author of the study and professor of medicine in the division of cardiology, Hopital Nord (North Hospital), University of Marseille, School of Medicine, Marseille, France.

The researchers studied 429 low responders, including 214 in the control group who got usual care with one 600 mg dose of clopidogrel. The test group received up to three more doses of clopidogrel every 24 hours with a goal of reducing their score to the cut-off level on a VASP phosphorylation analysis, a blood test that measures a patient's anti-platelet response to clopidogrel.

The primary endpoint was the rate of early definite stent thrombosis. That was defined as a total blockage or visible thrombus originating in or within 5 mm of the stent and associated with symptoms or diagnostic signs of reduced blood flow to the heart muscle within 48 hours of the procedure.

The secondary endpoints were the rate of a composite of major adverse cardiac events (MACE), which included myocardial infarction and cardiovascular death, or urgent revascularization procedures, as well as the separate endpoint of bleeding.

Despite additional doses of clopidogrel up to a total of 2400 mg, 8 percent of the low-responders remained with a low response. However, the tailored approach significantly lowered the primary and secondary event endpoints without significantly increasing bleeding events, said Paganelli. The rate of early definite stent thrombosis was 0.5 percent in the tailored-dosage patients versus 4.2 percent in the controls (p<0.01). The rate of MACE was substantially lower in the individualized treatment group: 0.5 percent vs. 8.9 percent for the controls.

Researchers found no statistically significant difference in bleeding incidents between the groups.

Co-authors are: Laurent Bonello, M.D.; Sebastien Armero, M.D.; Olivier Com, M.D.; Caroline Bonello, M.D.; Roland Bonello, M.D.; Marie Paule Giacomoni, M.D.; Frederic Collet, M.D.; Philippe Rossi, M.D.; Paul Barragan, M.D.; Laurence Camoin Jau, M.D., Ph.D.; and Francoise Dignat-George, M.D., Ph.D.

The authors report no funding source for this study.