| <P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><A name=sa></A><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2010</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">8</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">月</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">20</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">日，美国食品药品管理局（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）发布信息称，该局正在评估</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的心血管事件风险。因为临床试验数据显示，服用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的患者与服用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Sinemet</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的患者相比，其心血管事件（心脏病发作、脑卒中和心血管原因死亡）的发生风险可能升高。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">（卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">恩他卡朋）和</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Sinemet</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">（卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴）均为治疗帕金森病的有效药物。使用卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴外加恩他卡朋治疗，对帕金森病某些症状的改善幅度大于仅用卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴治疗。恩他卡朋也有单一成分的产品上市，商品名为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Comtan</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">。因为恩他卡朋本身没有抗帕金森病的作用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">,</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">所以该药总是与卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴合用。据估计，自</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2003</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">月</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">获准上市至</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2009</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">10</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">月底，医疗专业人员已为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">15.4</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">万患者开具了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">处方。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">一项名为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的试验发现，与仅用卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴的患者相比，用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗的患者报告心肌梗塞的数量增加。虽然曾报道左旋多巴有心肌梗塞、心律不齐、高血压和心悸等不良事件，但此前</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的临床试验中未见心肌梗塞、脑卒中和心血管原因死亡的报告率异常升高。然而，这些试验大多数持续时间</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">≤6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">个月，报告的事件数量也相对较少。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验中，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">373</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例患者接受</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">372</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例患者接受卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴治疗；疗程为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2.6-4</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年，中位疗程</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2.7</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年；患者的平均年龄约为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">60</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">岁。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">组报告了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">7</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例心肌梗塞和</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例心血管原因死亡，而卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴组没有心肌梗塞和心血管原因死亡的报告。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">鉴于</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的研究结果，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">开展了一项包含</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">15</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">项临床试验的荟萃分析，共包括</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">4,800</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名患者，将恩他卡朋</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴复方药与卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴复方药进行了比较。心血管事件终点为心肌梗塞、脑卒中和心血管原因死亡。恩他卡朋</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴组报告了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">27</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例心血管事件，卡比多巴</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">左旋多巴组报告了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">10</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例，相对风险为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2.46</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">95%</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">可信区间：</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1.19, 5.09</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）。将</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验的数据从分析中剔除，则相对风险为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1.67</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">95%</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">可信区间：</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">0.77, 3.61</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">），即这个结果不再有统计学意义。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">虽然包括</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验的荟萃分析结果有统计学意义，但因为存在下列因素，所以很难根据这一发现得出可靠的结论：</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">包含在荟萃分析中的试验不是专门为评价</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的心血管安全性而设计的。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"> <SPAN></SPAN></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">多数患者原本就有心血管疾病的危险因素。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">其中</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">11</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">项试验的持续时间</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"><6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">个月，不足以评价心血管风险（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验中的</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">8</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例事件，有</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">7</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">例是在</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">个月之后发生的）。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"> <SPAN></SPAN></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· STRIDE-PD</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验结果对整个荟萃分析结果的影响较大，是导致产生安全性信号的主要原因。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">不良事件叙述信息不全，多数病例的心血管事件难以验证。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">荟萃分析是假设混杂因素在</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">15</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">项研究中通过随机化保持了组间平衡。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">没有停药或退出试验的数据，假定两个治疗组的任何停药或退出事件都与不良事件的风险无关。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">· </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">因无法获取每个病例的详细数据，所以不能进一步探讨混杂因素对结果产生的影响，也不能更好地评价</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">与心血管事件之间的因果关系。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-ALIGN: left; LINE-HEIGHT: 150%; TEXT-INDENT: 31.5pt" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">正在尝试用其他方法评价</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的心血管事件风险。目前，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">建议医疗专业人员定期检查服用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Stalevo</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的患者的心血管状况，特别是有心血管病史的患者；建议患者无医嘱不要擅自停药。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P> |
