OAT试验生活质量和成本效益分析数据支持其最初结论

Quality-of-life and economic data from OAT support original findings

 

      11月5日，奥兰多：2007年AHA学术分会公布了闭塞动脉试验（OAT）生活质量和成本效益分析结果，这进一步说明最初的结论――心肌梗死后稳定的患者单用最佳药物比行PCI术更好。用PCI治疗的患者感觉不如用药物治疗的患者，而且其费用也更高。

       OAT试验入选2,166名稳定型冠心病患者，心梗12-24小时内无有效心肌再灌注，随后出现完全闭塞动脉。像数年前该会报道的一样，与药物治疗相比，心梗后3～28天行晚期血管成形术，未能减少患者死亡、再梗死、心衰等事件发生几率。Duke临床研究院的Dan Mark医生本次报告最新试验结果是关于三个预计划、前瞻性的次要终点（生活质量、成本和成本效益），支持该试验最初结论：用PCI治疗2年所花费用要比药物治疗高7000美元。

 

　　AHA学术委员会主席Gordon医生为心脏在线推荐这些结论时说：“这些结果说明至少早期行PCI术费用会更高，收益也不大。若患者有一支动脉闭塞，而其他正常，我们就应该选择药物治疗。

 

　　Brahmajee医生在讨论时说：“这项亚组研究设计严谨，对生活质量和成本效益数据检测仔细。PCI提高生活质量作用甚小，花费却更高的结论，让惯用PCI的医生毫无争论余地。”

 

      仅美国组完成OAT分析

 

       三个主要的计划前瞻性分析分别是ITT（意向处理）生活质量分析、ITT花费分析和ITT效益分析。Mark医生解释说抽查者最初计划对所有OAT试验的患者进行分析，但最终由于条件限制仅对美国组患者进行了分析。

 

　　951名患者的两项主要生活质量检测参数是杜克活动度状态指数（DASI，反映患者的身体活动程度）和SF-36心理健康评估。尽管PCI组和药物治疗组一年及以上DASI得分无差异，但PCI组治疗初期略有优势。PCI组和药物组两年的SF-36数值无临床差异和统计学意义。

 

       像心绞痛和呼吸困难等次要终点，PCI组有优势，但在研究结束时两组差异极小。Mark医生说他正筹划第二阶段的OAT试验，搜集患者五年生活质量的数据，希望能证实今天的结论。

 

       在试验初期进行成本效益分析的患者不多，仅有469名。仅医疗基线一项，PCI组花费就比药物组高出9,000美元（p<0.0001）。但两组随访花费相似，PCI两年净额达7,050美元。

       新的分析结果更加支持OAT试验

 

        综合复式模拟法得出的费效分析结果，Mark医生及其同事发现在65%的病例中，最佳药物组治疗效果优于PCI组。

Mark医生说：“成本效益分析显示了PCI策略较单纯应用最佳药物治疗两年花费更高，其仅有的微小症状改善不足以确立在OAT入选病例中应用PCI的手术策略。”他同时强调：“药物治疗花费较低，且能更好的改善患者存活质量，而PCI则不符合介入治疗的经济门槛。”

 

       Nallamothu医生说生活质量和成本效益分析有三个理由可以支持OAT试验：一是OAT试验的次要终点分析得出混合结果；二是心梗后通常应用血运重建术，特别是在美国这样已应用数年的国家；三是两种策略的花费依然不清楚，被推荐的策略可能有政策性意味。

 

       新的分析结果显示“该研究的PCI显然并不是一种经济有效的策略，” Nallamothu解释说：“它不能与任何通常有效的策略相比，如直接PCI，应用自动体外除颤仪，ACS给予高剂量他汀类药物，或晚期肾病透析诊断金标准。”

 

       更广泛的观察

 

       Mark详述了心脏在线的问题。“如果你观察过去几十年血运重建术及其研究类型，就会发现只有少数研究将PCI和药物治疗进行对比。其中大部分还假设需要行PCI术，即他们需要穿着铅服工作，但问题是穿什么样的铅服工作？”

 

       “一旦你明白了COURAGE这个关于稳定型心绞痛的试验时，你也就明白了有关稳定型心梗的OAT试验。这两个试验都显示药物治疗具有优势，且很难看出穿着铅服做PCI对医用花费及延长寿命具有真正的价值。”

 

       当问及是否考虑到OAT试验结果已被内科医生接受并应用到工作中时，Mark医生说：“这很难讲，因为无法跟踪调查，以我个人的经验来看，OAT在这里解释的并不好，因为仍有一些我们常见的血运重建情况――医生进入导管室，做手术和力所能及的事；他们已经养成习惯给每一位心梗患者做导管治疗，而且也能把这个做得非常好――成功率高，风险相对低，人们也期望这么做。只要血管造影诊断与PCI术紧密结合，它就像火车一样在启动后很难停下来。

 

       Mark认为美国医疗体制被指责是因为医生们“没有得到相应的薪酬。如果稍稍提高些收入并且如果你患病时能再多付些医药费”，那就可能会不一样了。“例如在加拿大，他们的政策就包括以上的这些内容，因此对他们来说更加真实，我们也必须在体制上有一些变化。”

 

       (www.theheart.org)

 

Quality-of-life and economic data from OAT support original findings

 

November 5, 2007  

 

Lisa NainggolanOrlando, FL - Further quality-of-life and economic analysis of the Occluded Artery Trial (OAT), reported here today at American Heart Association 2007 Scientific Sessions, support and reinforce the original conclusions of the study—that it is best to treat stable post-MI patients with optimal medical therapy alone rather than PCI. Those treated with PCI felt no better than those on medical therapy, and PCI was more expensive.

 

OAT was conducted in 2166 stable patients who had had an MI but who had not gotten effective reperfusion within 12 to 24 hours and were subsequently found to have a totally occluded artery. Performing late angioplasty on the occlusion three to 28 days after MI did not reduce rates of death, reinfarction, or heart failure compared with optimal medical therapy, as reported a year ago at this meeting. Presenting the new findings today, Dr Dan Mark (Duke Clinical Research Institute, Durham, NC) said three preplanned prospective secondary end points—quality of life, cost, and cost-effectiveness—did not alter that conclusion and in fact showed that PCI cost $7000 more than optimal medical therapy over two years.

 

Commenting on the findings for heartwire, chair of the AHA Scientific Sessions program committee, Dr Gordon Tomaselli (Johns Hopkins University, Baltimore, MD), said: "These results show that, at least early on, doing PCI is more expensive and not more effective. In patients who have a closed artery but are otherwise doing well, we should probably just leave those people alone and treat them medically."

 

Discussant of the study, Dr Brahmajee K Nallamothu (Ann Arbor, MI), said: "This substudy had a strong design, with careful measurement of quality of life and costs. The benefits in quality of life were marginal and costs were high with PCI, and this really leads to the finding that there is no quality-of-life or economic argument that supports routine PCI in this important population of patients."

 

Analyses done only in US cohort of OAT

 

The three major analyses planned prospectively were quality of life by intention-to-treat (ITT) analysis, cost by ITT analysis, and a cost-effectiveness analysis. Mark noted that the investigators had originally planned to include all the OAT patients but in the end had to restrict analyses to US patients only, something both he and Nallamothu noted was a limitation.

 

The two main quality-of-life parameters examined in 951 patients were the Duke Activity Status Index (DASI)—which is a measure of how physically active patients are able to be—and the SF-36 Mental Health Inventory. The DASI scores showed no difference between the PCI and medical-therapy groups at one year and beyond, although there was an initial advantage for the PCI-treated patients. There were no clinically significant or statistically significant differences in the SF-36 between the two groups of patients after two years.

 

Other secondary end points, such as angina and dyspnea, showed some differences in favor of the PCI group, but these differences were small by the end of the study.

 

Mark said a second phase of OAT is now planned, to collect five-year quality-of-life data: "I hope to be able to prove that what I’ve said today is actually true, and not have to retract it."

 

The economic analysis was conducted on even fewer patients, just 469 of those in the original study. Baseline medical costs were about $9000 higher in the PCI arm than in the medical arm (p<0.0001). Follow-up medical costs for the two arms were similar, with a two-year net cost for PCI of $7050.

 

New analyses add substantially to OAT

 

Putting this all together with a formal cost-effectiveness analysis that used bootstrap simulation, Mark and colleagues found that optimal medical therapy dominated PCI in 65% of cases.

 

"The economic analysis shows that a strategy of routine PCI was substantially more expensive than optimal medical therapy alone out to two years, and the small symptom benefits provided were insufficient to make PCI an economically active strategy in OAT-eligible patients," Mark said. "Medical therapy is less expensive and gives better quality-adjusted survival. PCI does not meet the threshold for economic intervention," he stated.

 

Nallamothu said the quality-of-life and economic analyses "add substantially to OAT for three reasons. First, the secondary end points in the primary OAT analysis showed mixed results. Second, revascularization is commonly used in this patient population after MI, particularly in the US, where this practice has been embedded for a number of years. And finally, the costs associated with both approaches remained unclear, and that had important policy implications for which of these strategies might be preferred."

 

This new analysis has shown that "PCI in this study is clearly not a cost-effective strategy," Nallamothu noted. "It doesn’t compare at all to [cost-effective strategies in medicine generally], such as primary PCI, the use of automated external defibrillators, high-dose statins in ACS, or the gold standard of dialysis in end-stage renal disease."

Looking at the bigger picture

 

Mark expanded upon the issues for heartwire. "If you look at the big picture about revascularization and the types of studies that have been done over the past decade or more, there’s a small handful of studies that have compared PCI with medical therapy. Most of them have started from the presumption that PCI needs to be done—they need the plumbing work, the question is what type of plumbing work?"

 

"But then you’ve got COURAGE, which is stable angina, you’ve got OAT, which is post-MI patients who are stabilized and don’t have an acute indication for intervention, and in each the background is top medical therapy. It is extraordinarily difficult to show that doing plumbing work in that context is really good value for money or adds to the patient’s long-term health."

 

Asked whether he thought the OAT results had actually been taken on board by physicians, Mark said: "It’s hard to say, because there is no way of tracking it. My own totally anecdotal experience is that it’s not translating very well, because there is still this ocular revascularization reflex—people get into the cath lab, they do these cases, they want to do something, and they have the capability. We’ve gotten into the habit of cathing everybody after MI now, and it’s not like they can’t do a good job with it—the success rate is high, the risk to the patient is relatively low, and people sort of feel that they are expected to do something. As long as the diagnostic angiogram is coupled so tightly to the performance of PCI, it’s very hard to stop that train once it’s started."

 

Mark says the structure of the US healthcare system is partly to blame, because doctors "get paid for doing more stuff. If we got paid in a way that said, Be smart about what you do, and if you spend too much money you’re going to get in trouble,’’ it might be different. "In Canada, for example, where they do have these sort of caps, it becomes much more real to them. There are going to have to be structural changes."