{"id":27552,"date":"2025-03-06T04:13:00","date_gmt":"2025-03-05T20:13:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=27552"},"modified":"2025-03-06T05:57:36","modified_gmt":"2025-03-05T21:57:36","slug":"nejm%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9avutrisiran%e6%b2%bb%e7%96%97%e8%bd%ac%e7%94%b2%e7%8a%b6%e8%85%ba%e7%b4%a0%e8%9b%8b%e7%99%bd%e6%b7%80%e7%b2%89%e6%a0%b7%e5%8f%98%e6%80%a7%e4%bc%b4","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=27552","title":{"rendered":"[NEJM\u53d1\u8868\u8bba\u6587]\uff1aVutrisiran\u6cbb\u7597\u8f6c\u7532\u72b6\u817a\u7d20\u86cb\u767d\u6dc0\u7c89\u6837\u53d8\u6027\u4f34\u5fc3\u808c\u75c5"},"content":{"rendered":"\n

ORIGINAL ARTICLE<\/a><\/p>\n\n\n\n

Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy<\/h1>\n\n\n\n

Marianna\u00a0Fontana,\u00a0John L.\u00a0Berk,\u00a0Julian D.\u00a0Gillmore,\u00a0et al<\/h3>\n\n\n\n

N Engl J Med\u00a02025;392:33-44<\/h3>\n\n\n\n

DOI: 10.1056\/NEJMoa2409134<\/h3>\n\n\n\n

Abstract<\/h2>\n\n\n\n

BACKGROUND<\/h3>\n\n\n\n

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, fatal disease. Vutrisiran, a subcutaneously administered RNA interference therapeutic agent, inhibits the production of hepatic transthyretin.<\/p>\n\n\n\n

\u8f6c\u7532\u72b6\u817a\u7d20\u86cb\u767d\u6dc0\u7c89\u6837\u53d8\u6027\u4f34\u5fc3\u808c\u75c5\uff08ATTR-CM\uff09\u662f\u4e00\u79cd\u4e0d\u65ad\u8fdb\u5c55\u7684\u81f4\u6b7b\u6027\u75be\u75c5\u3002vutrisiran\u662f\u4e00\u79cd\u76ae\u4e0b\u6ce8\u5c04\u7684RNA\u5e72\u6270\u6cbb\u7597\u5242\uff0c\u53ef\u6291\u5236\u809d\u810f\u5185\u8f6c\u7532\u72b6\u817a\u7d20\u86cb\u767d\u7684\u751f\u6210\u3002<\/p>\n\n\n\n

METHODS<\/h3>\n\n\n\n

In this double-blind, randomized trial, we assigned patients with ATTR-CM in a 1:1 ratio to receive vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The primary end point was a composite of death from any cause and recurrent cardiovascular events. Secondary end points included death from any cause, the change from baseline in the distance covered on the 6-minute walk test, and the change from baseline in the Kansas City Cardiomyopathy Questionnaire\u2013Overall Summary (KCCQ-OS) score. The efficacy end points were assessed in the overall population and in the monotherapy population (the patients who were not receiving tafamidis at baseline) and were tested hierarchically.<\/p>\n\n\n\n

\u5728\u8fd9\u9879\u53cc\u76f2\u968f\u673a\u8bd5\u9a8c\u4e2d\uff0c\u6211\u4eec\u4ee51:1\u6bd4\u4f8b\u5206\u914dATTR-CM\u60a3\u8005\u63a5\u53d7vutrisiran\uff0825 mg\uff09\u6216\u5b89\u6170\u5242\u6cbb\u7597\uff0c\u6bcf12\u5468\u4e00\u6b21\uff0c\u6700\u957f\u6301\u7eed36\u4e2a\u6708\u3002\u4e3b\u8981\u7ec8\u70b9\u662f\u7531\u5168\u56e0\u6b7b\u4ea1\u548c\u590d\u53d1\u6027\u5fc3\u8840\u7ba1\u4e8b\u4ef6\u6784\u6210\u7684\u590d\u5408\u7ec8\u70b9\u3002\u6b21\u8981\u7ec8\u70b9\u5305\u62ec\u5168\u56e0\u6b7b\u4ea1\u30016\u5206\u949f\u6b65\u884c\u8ddd\u79bb\u4e0e\u57fa\u7ebf\u76f8\u6bd4\u7684\u53d8\u5316\uff0c\u4ee5\u53ca\u582a\u8428\u65af\u57ce\u5fc3\u808c\u75c5\u95ee\u5377\u603b\u5206\uff08KCCQ-OS\uff0cKansas City Cardiomyopathy Questionnaire\u2013 Overall Summary\uff09\u4e0e\u57fa\u7ebf\u76f8\u6bd4\u7684\u53d8\u5316\u3002\u7597\u6548\u7ec8\u70b9\u5728\u603b\u4f53\u4eba\u7fa4\u548c\u5355\u836f\u6cbb\u7597\u4eba\u7fa4\uff08\u57fa\u7ebf\u65f6\u672a\u63a5\u53d7tafamidis\u6cbb\u7597\u7684\u60a3\u8005\uff09\u4e2d\u8bc4\u4f30\uff0c\u5e76\u8fdb\u884c\u5e8f\u8d2f\u68c0\u9a8c\u3002<\/a><\/p>\n\n\n\n

RESULTS<\/h3>\n\n\n\n

A total of 655 patients underwent randomization; 326 were assigned to receive vutrisiran and 329 to receive placebo. Vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events than placebo (hazard ratio in the overall population, 0.72; 95% confidence interval [CI], 0.56 to 0.93; P=0.01; hazard ratio in the monotherapy population, 0.67; 95% CI, 0.49 to 0.93; P=0.02) and a lower risk of death from any cause through 42 months (hazard ratio in the overall population, 0.65; 95% CI, 0.46 to 0.90; P=0.01). Among the patients in the overall population, 125 in the vutrisiran group and 159 in the placebo group had at least one primary end-point event. In the overall population, treatment with vutrisiran resulted in less of a decline in the distance covered on the 6-minute walk test than placebo (least-squares mean difference, 26.5 m; 95% CI, 13.4 to 39.6; P<0.001) and less of a decline in the KCCQ-OS score (least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P<0.001). Similar benefits were observed in the monotherapy population. The incidence of adverse events was similar in the two groups (99% in the vutrisiran group and 98% in the placebo group); serious adverse events occurred in 62% of the patients in the vutrisiran group and in 67% of those in the placebo group.<\/p>\n\n\n\n

\u5171\u8ba1655\u4f8b\u60a3\u8005\u63a5\u53d7\u4e86\u968f\u673a\u5206\u7ec4\uff0c\u5176\u4e2d326\u4eba\u88ab\u5206\u914d\u63a5\u53d7vutrisiran\u6cbb\u7597\uff0c329\u4eba\u88ab\u5206\u914d\u63a5\u53d7\u5b89\u6170\u5242\u6cbb\u7597\u3002vutrisiran\u4e0e\u5b89\u6170\u5242\u76f8\u6bd4\u964d\u4f4e\u4e8642\u4e2a\u6708\u65f6\u7684\u5168\u56e0\u6b7b\u4ea1\u548c\u590d\u53d1\u6027\u5fc3\u8840\u7ba1\u4e8b\u4ef6\u98ce\u9669\uff08\u603b\u4f53\u4eba\u7fa4\u4e2d\u7684\u98ce\u9669\u6bd4\uff0c0.72\uff1b95%\u7f6e\u4fe1\u533a\u95f4[CI]\uff0c0.56~0.93\uff1bP=0.01\uff1b\u5355\u836f\u6cbb\u7597\u4eba\u7fa4\u4e2d\u7684\u98ce\u9669\u6bd4\uff0c0.67\uff1b95% CI\uff0c0.49~0.93\uff1bP=0.02\uff09\uff0c\u4e5f\u964d\u4f4e\u4e86\u5168\u56e0\u6b7b\u4ea1\u98ce\u9669\uff08\u98ce\u9669\u6bd4\uff0c0.65\uff1b95% CI\uff0c0.46~0.90\uff1bP=0.01\uff09\u3002vutrisiran\u7ec4163\u4f8b\u60a3\u8005\u548c\u5b89\u6170\u5242\u7ec4202\u4f8b\u60a3\u8005\u53d1\u751f\u4e86\u4e3b\u8981\u7ec8\u70b9\u4e8b\u4ef6\u3002\u5728\u603b\u4f53\u4eba\u7fa4\u4e2d\uff0cvutrisiran\u4e0e\u5b89\u6170\u5242\u76f8\u6bd4\u51cf\u5c0f\u4e866\u5206\u949f\u6b65\u884c\u8ddd\u79bb\u7684\u7f29\u77ed\u5e45\u5ea6\uff08\u6700\u5c0f\u4e8c\u4e58\u5e73\u5747\u5dee\u5f02\uff0c26.5 m\uff1b95% CI\uff0c13.4~39.6\uff1bP<0.001\uff09\uff0c\u4e5f\u51cf\u5c0f\u4e86KCCQ-OS\u8bc4\u5206\u4e0b\u964d\u5e45\u5ea6\uff08\u6700\u5c0f\u4e8c\u4e58\u5e73\u5747\u5dee\u5f02\uff0c5.8\u5206\uff1b95% CI\uff0c2.4~9.2\uff1bP<0.001\uff09\u3002\u00a0\u5728\u5355\u836f\u6cbb\u7597\u4eba\u7fa4\u4e2d\u4e5f\u89c2\u5bdf\u5230\u7c7b\u4f3c\u76ca\u5904\u3002\u4e24\u7ec4\u7684\u4e0d\u826f\u4e8b\u4ef6\u53d1\u751f\u7387\u76f8\u4f3c\uff08vutrisiran\u7ec499%\uff0c\u5b89\u6170\u5242\u7ec498%\uff09\uff1bvutrisiran\u7ec4\u4e25\u91cd\u4e0d\u826f\u4e8b\u4ef6\u53d1\u751f\u7387\u4e3a62%\uff0c\u5b89\u6170\u5242\u7ec4\u4e3a67%\u3002<\/p>\n\n\n\n

\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n

CONCLUSIONS<\/h3>\n\n\n\n

Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo and preserved functional capacity and quality of life. (Funded by Alnylam Pharmaceuticals; HELIOS-B ClinicalTrials.gov number,\u00a0NCT04153149<\/a>.)<\/p>\n\n\n\n

\u5728ATTR-CM\u60a3\u8005\u4e2d\uff0c\u4e0e\u5b89\u6170\u5242\u76f8\u6bd4\uff0cvutrisiran\u6cbb\u7597\u53ef\u964d\u4f4e\u5168\u56e0\u6b7b\u4ea1\u548c\u5fc3\u8840\u7ba1\u4e8b\u4ef6\u98ce\u9669\uff0c\u5e76\u6709\u52a9\u4e8e\u60a3\u8005\u4fdd\u6301\u529f\u80fd\u80fd\u529b\u548c\u751f\u6d3b\u8d28\u91cf\u3002\uff08\u7531Alnylam Pharmaceuticals\u8d44\u52a9\uff1bHELIOS-B\u5728ClinicalTrials.gov\u6ce8\u518c\u53f7\u4e3aNCT04153149\uff09\u3002<\/p>\n","protected":false},"excerpt":{"rendered":"

ORIGINAL ARTICLE Vutrisiran in Patients with Transthyre […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/27552"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=27552"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/27552\/revisions"}],"predecessor-version":[{"id":27553,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/27552\/revisions\/27553"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=27552"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=27552"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=27552"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}