FDA发布戒烟药畅沛的最新安全性信息

美国食品药品管理局(FDA)12月12日发布的有关戒烟药伐尼克兰(畅沛)的心血管安全性声明指出，Meta分析显示伐尼克兰组主要不良心血管事件(MACE)的发生率高于安慰剂组，但差异无统计学显著性。

2011年6月FDA在一项纳入稳定型心血管疾病患者的戒烟研究中首次发现伐尼克兰可导致心脏风险增加，因此其敦促该药生产商辉瑞公司进行Meta分析。

该Meta分析比较了辉瑞进行的15项随机双盲安慰剂对照研究中接受至少12周治疗者的MACE发生率。MACE为心血管相关死亡、非致死性心肌梗死(MI)和非致死性卒中的复合终点。在停药后30天内，伐尼克兰组的MACE发生率为0.31% (13例/4,190例)，而安慰剂组为0.21% (6例/2,812 例)。这相当于MACE增加6.3例/1,000暴露人年。

在不同时间点和预定敏感性分析(包括不同研究分组和心血管终点的分析)中均发现，尽管差异无显著性，但伐尼克兰组的复合终点发生率始终高于安慰剂组。

此外，伐尼克兰组的心血管死亡率和全因死亡率(MACE终点的组成部分)均低于安慰剂组，差异无显著性。伐尼克兰组的心血管死亡率为0.05%(2例)，而安慰剂组为0.07%(2例)。伐尼克兰组的全因死亡率为0.14%(6例)，而安慰剂组为0.25%(7例)。

烟碱受体部分激动剂伐尼克兰于2006年获得FDA批准。FDA指出，在截至2012年9月的12个月内，美国共开具230万份伐尼克兰处方，约126万例患者从门诊零售药店获得了该药处方。FDA在声明中建议医生在权衡伐尼克兰的风险和获益时应考虑戒除烟瘾后带来的即时显著健康获益，并指出伐尼克兰能够有效帮助患者戒烟且戒烟效果持续长达1年。另外，声明还建议，如果患者出现新的或加重的心血管疾病症状，则应就医。该Meta分析的结果已被加入该药标签的警告和注意事项部分。

药品安全通报信息可点此获取。伐尼克兰相关严重不良事件应向FDA报告，联系电话：800-332-1088。

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By: ELIZABETH MECHCATIE, Cardiology News Digital Network

The rate of major adverse cardiovascular events was higher among patients treated with varenicline than those on placebo in a meta-analysis, but the difference was not statistically significant, according to the latest Food and Drug Administration statement on the cardiovascular safety of the smoking cessation drug.

In the study, conducted by the manufacturer at the request of the FDA, major adverse cardiovascular events (MACEs), a composite endpoint of cardiovascular-related death, nonfatal MI, and nonfatal stroke, "were uncommon in both the Chantix and placebo groups, and the increased risk was not statistically significant, which means it is uncertain whether the excess risk for the Chantix group was due to the drug or due to chance," the FDA statement said. Varenicline, a nicotinic receptor partial agonist marketed as Chantix by Pfizer, was approved in 2006.
 
Courtesy CDC/Debora Cartagena

Patients treated with varenicline had a higher rate of major adverse cardiovascular events compared with patents on placebo, but the difference was not statistically significant.
 
The first notice issued by the FDA about the drug’s possible cardiac risks was in June 2011. That notice reported the increased risk in a smoking cessation trial of patients with stable cardiovascular disease, prompting the FDA to require the company to conduct the meta-analysis. The FDA statement, dated Dec. 12, says the findings of the meta-analysis are similar to the findings of the smoking cessation study.

The meta-analysis compared the MACE incidence of patients treated for at least 12 weeks, in 15 randomized, double-blind, placebo-controlled studies conducted by Pfizer. Within 30 days of stopping the drug, the incidence of MACE was 0.31% (13 cases among 4,190 patients) in those on the drug, compared with 0.21% (6 cases among 2,812 on placebo). This is comparable to an increase of 6.3 MACE cases per 1,000 patient years of exposure, the FDA said.

In the study, the rates of composite outcomes were higher among those on varenicline "across different time frames and prespecified sensitivity analyses, including various study groupings and cardiovascular endpoints," and while not significantly different, they were consistent, the statement said.

The FDA also points out that cardiovascular mortality and all-cause mortality, components of the MACE endpoint, were lower among the patients on varenicline, although the differences were not significant. The rate of cardiovascular mortality was 0.05% (two cases) among those on varenicline, compared with 0.07% (two cases) among those on placebo. The rate of all-cause mortality was 0.14% among those on varenicline (6 cases), compared with 0.25% (7 cases) among those on placebo.

In the statement, the FDA advises that when weighing the risks and benefits of varenicline, health care professionals should consider the "immediate and substantial" health benefits of quitting smoking, and that "Chantix is effective in helping patients to quit smoking and abstain from it for as long as one year," the FDA advised in the statement. Patients should also be counseled to seek medical help if they develop new or worsening cardiovascular disease symptoms during treatment with varenicline, the statement added.

The results of the meta-analysis have been added to the warnings and precautions section of the drug’s label.

About 2.3 million varenicline prescriptions were dispensed and about 1.26 million patients received prescriptions for the drug from outpatient retail pharmacies in the United States, during the 12-month period ending in September 2012, according to the FDA.

The safety communication is available here. Serious adverse events associated with varenicline should be reported to the FDA at 800-332-1088 or here.