[TCT2008]新型抗血小板药物普拉格雷快速有效

新型抗血小板药物普拉格雷快速有效

Analysis Confirms Speed, Efficacy of Prasugrel

（北京武警总医院 韩玮 翻译）

TCT 2008上发布的一个摘要显示新型口服抗血小板药物普拉格雷比氯吡格雷能更有效抑制血小板聚集。研究者来自Eli Lilly、Company和Daiichi Sankyo，联合开发用于PCI从普拉格雷，研究分析了23个独立临床试验的资料。

研究者开展了以前研究的整合分析，普拉格雷先给予60mg的负荷量，然后每天10mg的维持量，氯吡格雷是300mg的负荷量和75mg的维持量，结果表明普拉格雷比氯吡格雷抑制血小板聚集更快、更强和更持久。

该研究分析了23个试验的750例患者，服用普拉格雷和氯吡格雷，研究者采用浊度测定聚集法评价对5 µm和20µmADP诱导的血小板聚集抑制的功能。总的来说应用普拉格雷患者负荷量和随访任何时间点的血小板聚集抑制都比氯吡格雷要快速和更有效，用负荷量后普拉格雷最大血小板抑制率是79%，氯吡格雷组是44%（P<0.01），另外负荷量一个小时后血小板抑制率超过50%在普拉格雷组是89%，氯吡格雷组是10%（P<0.001），平均稳定状态血小板抑制普拉格雷组是69%，氯吡格雷组是49%。

Li指出该分析也证实10mg 普拉格雷有较低的药代动力学反应不佳的发生率，而氯吡格雷组75mg每天大约有一半的个体反应不佳，研究者指出普拉格雷快速有效的原因在于在体快速转变为活性代谢产物。

TRITON TIMI研究

普拉格雷和氯吡格雷的对比研究有助于解释TRITON-TIMI 38研究结果，TRITON-TIMI 38三期临床试验发表在2007年的NEJM上，入选了13,608例中高危急性冠脉综合征患者，比较两种抗血小板药物的安全性和有效性。

“该试验发现普拉格雷有更低的复合终点包括心血管死亡、非致死性心梗和非致死性卒中，同时普拉格雷治疗的患者也有更高的严重出血事件，这些可能和普拉格雷更有力抑制血小板聚集有关”。TRITON-TIMI 38 结论是普拉格雷在防止缺血事件上比氯吡格雷策略更有效，但要警惕严重致死性出血事件的危险。

（来源：www.tctmd.com）

Analysis Confirms Speed, Efficacy of Prasugrel

By TCT Daily News Staff

The oral antiplatelet drug prasugrel produces faster, more consistent inhibition of platelet aggregation than clopidogrel, according to an abstract presented at TCT 2008.

Investigators from Eli Lilly and Company and Daiichi Sankyo, which are jointly developing a formulation of prasugrel for percutaneous coronary intervention, analyzed data obtained from 23 individual clinical trials involving healthy participants with stable atherosclerosis.

Researchers conducted an an integrated analysis of the previous trials, which had demonstrated previously that a 60-mg loading dose of prasugrel followed by a 10-mg daily maintenance dose produced “faster, higher and more consistent inhibition of platelet aggregation than did a clopidogrel loading dose of 300 mg followed by a 75-mg daily dose,” Grace Y. Li, MS, project statistician with Eli Lilly, said in an interview.

Results and analysis

The integrated data analysis evaluated outcomes in 750 patients from 23 trials who were assigned to take either prasugrel or clopidogrel. Researchers used turbidometric aggregometry to assess inhibition of platelet aggregation in response to 5 µm and 20 µm adenosine diphosphate.

Overall, patients treated with prasugrel experienced faster and more effective inhibition of platelet aggregation after the loading dose and at all subsequent follow-up points, the researchers reported. The group assigned to take prasugrel achieved 79% mean maximum inhibition of platelet aggregation after the loading dose, compared with 44% in the clopidogrel group (P < .001). In addition, approximately 89% of patients receiving prasugrel reached >50% inhibition of platelet aggregation vs. 10% of subjects receiving clopidogrel within one hour following the loading dose (P < .0001). Higher and more consistent inhibition was observed for prasugrel vs. clopidogrel during maintenance with a mean steady state inhibition of 69% for prasugrel and 49% for clopidogrel (P < .001).

“This analysis also demonstrated a very low incidence of pharmacodynamic poor responders to the 10-mg daily dose of prasugrel, regardless of the definition of poor responder,” Li said.

In contrast, up to half of subjects assigned the 75-mg daily dose of clopidogrel were categorized as “poor responders.”

Researchers surmise that prasugrel’s speed and efficacy of action are attributable to its more rapid conversion to an active metabolite in the body, Li explained.

Return to TRITON TIMI

The results seen with prasugrel compared with those with clopidogrel could help explain the results of the TRITON-TIMI 38 study, according to Ms. Li. The phase 3 TRITON-TIMI 38 trial, published in The New England Journal of Medicine in 2007, enrolled 13,608 patients with moderate- to high-risk acute coronary syndromes to compare the safety and efficacy of the two thienopyridine drugs.

“This [TRITON-TIMI 38] trial, conducted in patients with ACS undergoing PCI, showed that patients treated with prasugrel had a statistically significant lower rate of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke compared with clopidogrel-treated patients,” she said.

“Prasugrel-treated patients also had a significantly higher rate of major bleeding, which might have been expected given the more potent inhibition of platelet aggregation achieved with prasugrel.”

The TRITON-TIMI 38 study group concluded that the tested regimen of prasugrel was more effective in the patient population at preventing ischemic events than a standard regimen of clopidogrel. Yet they cautioned that the benefits must be weighed against the increased risk of major bleeding, which can be fatal.