Sildenafil治疗肺动脉高压症可能会有效果

    美国胸腔外科医师学会(American College of Chest Physicians)第70届年会上，一项任意性、辅以安慰剂控制组作为对照的研究指出，对于肺动脉高压(PAH)的患者而言，使用Sildenafil citrate作治疗，可以明显的改善患者的6分钟步行测试結果。
　　德国University of Giessen大学內科学系的Hoissein A. Ghofran医师表示，患者每日接受三次80 mg的sildenafil以后，可以改善其6分钟的步行能力；結果显示，增加的距离为50米；每日接受三次40 mg剂量的患者，在同样的测试条件下可以增加46米的距离；接受最低剂量者，也就是每日三次的20mg，可以增加45米的步行距离。
　　Ghofrani向Medscape表示，一項必须牢記的信息就是，sildenafil在临床试验时已经证明，此药物可以对心脏功能等级II(New York Heart Association, NYHA)的患者产生高度的疗效；有38%的患者为NYHA II，58%的患者为NYHA III。
　　Ghofrani医师进一步表示，除了能改善6分钟步行试验的结果之外，35%的试验组患者在心脏功能等級上也有进步；而在对照组中，心脏功能等级只有7%的患者获得进步；然而，平均肺动脉压力(mPAP)降低了5.1 mmHg，但这一项在统计上並沒有明显的差异。
　　用于肺动脉高压(SUPER-1)患者上的研究里，一共有278位患者参与试验，並以任意性的方式作分组；安慰剂对照組有70例，试验组患者每日皆接受三次的sildenafil，以不同剂量分为三组，每次剂量20mg者有69例，40mg者为68例，而80mg者则为71例；参与者中有75%为女性，平均年龄为49岁。
　　试验初期的数据分別为：6分钟步行距离为344米，mPAP为53 mmHg；结果发现，sildenafil的耐受性非常好，头痛是最常見的副作用，试验组一共有46例患者有此現象，但对照组也有39例；两组并无明显差异。
　  华府Walter Reed Army Medical Center的胸肺科医师Fitzgerald表示，虽然6分钟步行试验的结果在统计上有明显差异，但是临床上的影响还是很难评估。
　　Fitzgerald医师为SUPER-1发表会的主持人之一，他提出质疑指出，在12周的治疗期內，步行距离增加了50米，这代表了什么意义，我不确定这是否象征着真正的改善。
　　来自华盛顿州Tacoma的胸肺科医师，同时也是另一议程的主持人Alexander Niven表示，我同意，所得的数据的确是很难评估，因为PAH在临床上並沒有明确的试验终点，因此，我想如果能看到12个月的试验結果，那将会更有趣。
　　Ghofrani医师指出，采用80mg剂量的试验组目前正在继续进行中，这一组目前约完成了一半的试验期，試试验结果会将在6到12个月时出炉。
　　Niven医师同时表示，不管如何，我们乐于见到那另一项的口服试验，因为唯一核准用于PAH的口服药物bosentan(Trocleer, 由Actelion制药厂生产)非常昂贵，每年的用药成本约为四万元美金。

Sildenafil May Be Effective fo

By
Medscape Medical News

Peggy Peck

Oct. 28, 2004 (Seattle) — Sildenafil citrate produced significant improvement in six-minute walk test results of patients with pulmonary arterial hypertension (PAH), according to a randomized, placebo-controlled study presented here during a late-breaking clinical trials session at CHEST 2004, the 70th annual meeting of the American College of Chest Physicians.

Hoissein A. Ghofrani, MD, from the department of internal medicine at the University of Giessen in Germany, said patients receiving 80 mg of sildenafil three times daily increased "six-minute walk results by 50 meters, while patients receiving 40 mg of sildenafil three times daily increased their distance by 46 meters, and patients at the lowest dose [20 mg three times daily] increased by 45 meters." This was significant at P < .001.

The "take-home message is that sildenafil has been shown to be highly effective in a trial that for the first time included a significant proportion of [New York Heart Association (NYHA)] functional class II patients," Dr. Ghofrani told Medscape. Thirty-eight percent of the patients were NYHA class II and 58% were class III.

In addition to improved six-minute walk test results, 35% of patients in the pooled sildenafil groups improved functional class compared with 7% of patients in the placebo group, Dr. Ghofrani said. Moreover, mean pulmonary arterial pressure (mPAP) decreased by an average of 5.1 mm Hg, but this was not statistically significant.

The study, Sildenafil Use in Pulmonary Arterial Hypertension (SUPER-1), enrolled 278 patients randomized to placebo (n = 70) or to one of three doses of sildenafil three times daily: 20 mg (n = 69), 40 mg (n = 68), or 80 mg (n = 71). Seventy-five percent of the patients were women, and the mean age of patients was 49 years.

The mean baseline six-minute walking distance was 344 meters, and the baseline mPAP was 53 mm Hg.

Sildenafil was generally well tolerated, with headache as the most common adverse event (n = 46), but this was not significantly different from headache reported by placebo patients (n = 39).

Although the results for the six-minute walk test reached statistical significance, Thomas Fitzgerald MD, a pulmonologist at Walter Reed Army Medical Center in Washington, D.C., said that it is difficult to judge the clinical impact.

"An improvement of 50 meters on a walking test after 12 weeks of treatment? What does that really mean?" Dr. Fitzgerald asked. "I'm not sure that it is a sign of real improvement." Dr. Fitzgerald cochaired the late-breaking clinical trials session at which the SUPER-1 results were presented.

Alexander Niven, MD, the other session cochair, agreed that it is difficult to assess the data because "with PAH there are no hard clinical end points. I think it will be interesting to see the 12-month results." Dr. Niven is a pulmonologist at Madigan Army Medical Center in Tacoma, Washington.

A long-term trial is ongoing with patients "continuing at the 80-mg dose," Dr. Ghofrani said. The study is about halfway complete, and results will likely be available in six to 12 months, he said.

Dr. Niven added, however, that another oral treatment would be welcome because the only approved oral drug for PAH, bosentan (Trocleer; Actelion Pharmaceuticals) is expensive; Dr. Ghofrani estimated bosentan's annual cost at $40,000.

The SUPER-1 study was funded by Pfizer, the maker of sildenafil.

CHEST 2004: Late-breaking clinical trial session. Presented Oct. 27, 2004.