【报导】研究者预测COX-2 类药物面临撤市

Researchers See Chance U.S. Might Pull COX-2 Drugs

By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - Doctors who led three studies showing prescription painkillers called COX-2 inhibitors raise the risk of heart attacks and stroke said on Tuesday the whole class of drugs was in danger of being pulled from the market.

One day before a Food and Drug Administration (news - web sites) panel begins discussing the future of such drugs, the New England Journal of Medicine (news - web sites) published details of three studies stopped early because patients taking the drugs were having more heart attacks, strokes and other adverse events than patients not taking them.

"I think we are at risk of losing the class of drugs," said Dr. Robert Bresalier of the University of Texas M.D. Anderson Cancer Center, who was studying one of the drugs, Vioxx, known generically as rofecoxib, in a colon cancer trial.
Merck & Co. Inc. withdrew Vioxx in September after learning the results of Bresalier's trial, which showed Vioxx almost doubled the risk of heart attacks, strokes and other major adverse events.
Bresalier told reporters his trial also showed Vioxx worked at least as well as aspirin to prevent colon cancer. That data will be published later this year, he said.
He and other experts said those benefits would need to be weighed against the potential risks. "I think the loss of some of these drugs will create a void," he told reporters in a telephone briefing.
But Dr. Jeffrey Drazen, editor of the New England Journal of Medicine, said that since there were well-established alternatives to those drugs, "it is reasonable to ask whether the use of the drugs can now be justified."

The drugs are sold mainly for long-term pain relief in arthritis and other conditions.

TRIPLING MORTALITY

In a second report published by the journal, Dr. Scott Solomon and colleagues at Brigham and Women's Hospital and Harvard Medical School (news - web sites) found Pfizer Inc.'s Celebrex doubled or even tripled deaths from heart attack, stroke or heart failure, depending on the dose.
Their study involved more than 2,000 patients who were also taking the drug to see if it could prevent colon cancer.
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In a third report, Dr. Nancy Nussmeier of the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston and colleagues detailed their study using a third agent, Pfizer's Bextra, in heart surgery patients.
They found that 7.4 percent of those given the drugs had an adverse event -- such as heart attacks, kidney failure, ulcers and complications of wound healing -- compared with 4 percent of those given placebo alone.
The studies are among several others showing the drugs raise heart risks.
Ironically, COX-2 inhibitors, which have only been on the market for six years, were designed to be safer than aspirin and related drugs called non-steroidal anti-inflammatory drugs or NSAIDS.
NSAIDS affect two compounds made in the body called prostaglandins -- COX-1 and COX-2. Those drugs can also cause severe gastrointestinal bleeding in some people and kill an estimated 16,000 Americans a year.
The COX-2 inhibitors were meant to affect the inflammatory prostaglandin, cyclooxygenase-2, while leaving alone COX-1 and thus, drug makers hoped, sparing the stomach.
But they do not work any better than NSAIDS to relieve arthritis pain in most people.
Bresalier said for many people, acetaminophen, best known under its brand name Tylenol, was a good and safe choice.
"There is no pharmacologic agent out there that doesn't have great benefits or risks," he said.

http://story.news.yahoo.com/news?tmpl=story&ncid=751&e=1&u=/nm/20050215/hl_nm/health_cox_dc

华盛顿(路透社) - 三项研究显示被称为COX-2 抑制剂类的处方止痛药提高服药患者发作心脏病和中风的机率和风险, 主持这些研究的医生们星期二说, 他们相信这类药物可能需要整体从市场撤离。

在美国FDA开会讨论该类药物未来命运的前一天, 新英格兰医学学报发表了这三项临床试验的研究详情和结果, 这些研究由于发现患者服药后, 比对照组(未服用该药)有更多心脏病, 中风发作和其它有害事件发生而被及早停止。

"我认为我们有可能面临失去COX-2 抑制剂类药物的危险," 来自得克萨斯大学M 。D 。 安徒生肿瘤研究中心的罗伯特・Bresalier医学博士说, 罗伯特负责研究其中一种COX-2 抑制剂用于结肠癌临床应用的试验，该药商品名为Vioxx，其通用名为rofecoxib，由默克公司生产。 该公司在去年9月获悉Bresalier 的试验的结果以后，从市场撤出了Vioxx, 因为试验显示Vioxx 几乎加倍了心脏病中风和其他副作用发作发生的风险。

Bresalier 同时还告诉记者：他的试验显示在防止结肠癌方面Vioxx 工作至少与阿斯匹灵效果相仿。 相关数据将在今年下半年发表。 他和其它专家说那些已证实的临床价值需要与潜在临床风险权衡考虑。 "从市场撤离这些药物将创造一个空地和机会"。

但新英格兰医学学报的编辑Dr 。 Jeffrey Drazen持有不同看法, , 他认为以前已有多种被确认临床效果的其他止痛药物，由于COX-2 抑制剂问世而被人冷落，现在该是重新启用和调整临床用药方案的时候了。

在新英格兰医学学报发表的第二份有关COX-2 抑制剂危险性的报告中, 来自哈佛医学院Brigham 妇女医院的斯科特Solomon博士和同事发现Pfizer 公司的Celebrex 在高剂量下，使患者服药后因心脏病中风发作或心力衰竭而死亡的机率双倍甚至三倍增加。 他们的研究涉及超过2,000 名患者服用该药，同时观察是否能防止结肠癌。

在第三个报告中, 来自得克萨斯卢克主教医院心脏病研究所的南希Nussmeier博士和她的同事们，研究使用第三种药物：Pfizer 的Bextra, 用于心脏手术患者。
他们发现7.4% 的服药者经历一次毒副作用-- 譬如心脏病发作, 肾脏失败, 创伤愈合的溃疡和复杂化-- 安慰剂对照组只有4%发生毒副作用。其他几项研究也同样显示该药增大心脏损害的风险。

令人感到讽刺的是, COX-2 抑制剂, 仅仅只有上市六年的历史, 被设计和宣传为比阿斯匹灵和NSAIDS相关抗发炎药物更安全的药物。 NSAIDS 影响前列腺素的两种化合物-- COX-1 和COX-2 。 那些药物可能导致消化道严重出血导致每年估计16,000 美国人死亡。

COX-2 抑制剂被认为影响炎症前列腺素中的cyclooxygenase-2, 而不影响COX-1 和因而 如制药商希望的那样，可能对肠胃道相对安全。
  
但COX-2 抑制剂在疗效上并未比NSAIDS类药用于解除关节炎痛苦有任何改善。
Bresalier 说 对许多人而言, acetaminophen, 它的名牌名为Tylenol, 是一个好和安全选择。 "任何一种药物都有其临床用途和风险，否则就不成为药 ,"他说。