作者和AHA-ACC领导对风险计算器有信心

达拉斯——11月12日美国心脏病学会(ACC)和美国心脏协会(AHA)发布的新版美国胆固醇管理指南受到了较多批评，但指南作者们和这2家学会的领导仍然坚信这部指南是在抗击动脉粥样硬化性心血管疾病的战斗中迈出的一大步。

在11月18日举行的针对近1周来有关新指南的各方意见的紧急新闻发布会上，指南编撰小组的多位代表强调，这部指南中介绍的新心血管风险计算公式反映了如今最好和最全面的证据。

他们还强调，指南不提倡单纯使用公式和严格的风险阈值来判断患者是否应该接受他汀类药物治疗，而是告诉医生和患者应将风险计算器当做围绕他汀类药物治疗潜在风险和获益的讨论的起点。

AHA主席Mariell Jessup博士指出：“我认为这是迄今为止审查最仔细的一部指南。我们坚信这部指南是以最佳证据为基础的。”ACC/AHA 预防指南委员会主席、北卡罗来纳大学的Sidney Smith博士表示：“我们打算进一步推行这些指南。”

争论始于2名哈佛医学院、布里格姆妇女医院研究者的分析。从新指南发布当天，Paul M. Ridker博士和Nancy R. Cook博士就开始将新指南中的风险计算器应用于3个数据库中：女性健康研究、医生健康研究和女性健康倡议观测性研究。他们发现，风险计算器对动脉粥样硬化性心血管疾病(ASCVD)事件10年发生率高估了75%~150%，比在这3个队列中观察到的实际风险高出了1倍。这2名作者的分析结果发表在《柳叶刀》杂志11月19日在线版上。


Donald Lloyd-Jones博士

这2名研究者写道：“根据计算，在新指南认为需要接受他汀类药物治疗的3300万美国人中，可能多达40%~50%的人的风险实际上并未超过建议治疗的7.5%阈值。这种程度的预测误差已经无法忽略了，必须在广泛应用这种新的预测模型之前进行调校。“

《纽约时报》在上周末刊登了这项分析，并在本周一形容风险计算器对风险的高估“很尴尬”，还引用了一些著名心脏病专家“推迟使用新指南和风险计算器”的呼吁。

设计这种风险计算器的研究者承认这一工具存在缺陷，并表示已经在论文中指出了这一点，但同时强调，这种风险计算器相对于此前的指南——已被使用了12年之久的第3版成年人治疗专家组(ATPⅢ)——是一大进步，尤其是因为它将卒中作为动脉粥样硬化性心血管疾病(ASCVD)的一个终点纳入到风险计算中，并且依赖于含有相当大数量非裔美国人的数据库，而这两项特点是ATPⅢ不具备的。

风险计算器研发专家组共同主席、西北大学预防医学教授Donald Lloyd-Jones博士在接受采访时指出：“风险计算器永远都不会是完美的，但相比12年前，我们的确迈出了一大步。这种风险计算器能更好地计算女性(通过在结局指标中纳入卒中)、非裔美国人和白人男性的风险。我们对自己已经取得的进展感到非常自豪，而随着证据的不断积累，我们也非常乐于进一步完善它。你当然可以批评这种计算器，但我确实不知道还有哪种工具比它更好。”

其他领导新指南编撰的专家也强调，他们并不主张对所有风险计算值≥7.5%的人都盲目地使用他汀类药物。


Neil Stone博士

ACC/AHA指南编撰专家组共同主席、西北大学内科学-心脏病学教授Neil Stone博士表示：“没有人说过患者自然会获得他汀类药物。我们说的是，患者和医生需要对风险进行讨论，原因是有时候风险计算值是有意义的而有时候则不然。我们这是第一次将临床医生的个人判断和患者的个人偏好纳入指南中。风险计算是医生和患者之间讨论的起点而不是终点。”

他还指出，指南包含一个内置的“缓冲带”，原因是“有证据表明他汀类药物甚至对10年ASCVD事件风险仅有5%的患者也是有效的”。

该指南称，对于10年ASCVD事件风险≥7.5%且没有需要他汀治疗的其他风险的中年人而言，给予他汀类药物是“合理的”，并且指出在开始他汀类药物治疗之前，医患双方就患者的个体风险水平、他汀类药物治疗的潜在风险和获益，以及患者的个人偏好进行讨论是“合理的”。

Ridker博士和Cook博士表示，除了对风险计算器提出批评之外，他们对整部指南表示赞赏，称新指南是“在正确方向上迈出的重要一步”。

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By: MITCHEL L. ZOLER, Cardiology News Digital Network

DALLAS – In the face of high-profile criticism of the new U.S. cholesterol-management guidelines released by the American College of Cardiology and American Heart Association on Nov. 12, the physicians who crafted the guidelines, as well as the leadership of the two organizations, stood firmly behind the work, reiterating that it is a big step forward in the battle against atherosclerotic cardiovascular disease.

During a last-minute press conference called on Monday morning, Nov. 18, to address concerns that first bubbled up over the prior weekend, a series of representatives from the guideline-writing panel stressed that the new cardiovascular-risk-calculation formula introduced in the guidelines reflected the best and most comprehensive evidence available today.

They also stressed that the guidelines do not advocate simply using the formula and a rigid risk-threshold to decide whether or not a patient should receive a statin, but instead tell physicians and their patients to use the risk calculator as the starting point for a discussion of the risks and benefits that statin treatment might pose for each person.

"I think these are these are the most carefully vetted guidelines ever published," said Dr. Mariell Jessup, AHA president. "We’re confident that they are based on the best evidence."

"We intend to move forward with implementation of these guidelines," said Dr. Sidney Smith, professor of medicine at the University of North Carolina in Chapel Hill and chair of the ACC/AHA subcommittee on prevention guidelines.

The controversy began with an analysis run by two Harvard researchers starting on the day the guidelines and risk calculator came out that applied the new risk calculator to three databases at their immediate disposal, the Women’s Health Study, the Physicians’ Health Study, and the Women’s Health Initiative Observational Study. They found that the risk calculator overestimated the 10-year rate of atherosclerotic cardiovascular disease (ASCVD) event by 75%-150%, doubling the actual, observed risk in these three cohorts. The authors of the analysis, Dr. Paul M. Ridker and Nancy R. Cook, Sc.D., of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, published their results in a brief article published online in the Lancet on Nov. 19.
 
Based on their calculations, "it is possible that as many as 40% to 50% of the 33 million Americans targeted by the new guidelines for statin therapy do not actually have risk thresholds exceeding the 7.5% level suggested for treatment," the two researchers wrote. "Miscalibration to this extent should be reconciled and addressed ... before these new prediction models are widely implemented."

Their analysis was made available to the New York Times over the weekend, which led to a prominent story in the newspaper’s Nov. 18 edition that called this overestimate by the risk calculator a "major embarrassment," and quoted some prominent cardiologists who also called for a delay in implementation of the new guidelines and risk calculator.

The researchers who devised the calculator responded by acknowledging the flaws in the device, something they had already done in their manuscript, but stressed that it represented a major improvement over the risk calculator from the prior guidelines, the third edition of the Adult Treatment Panel (ATP III) used for the past 12 years, particularly because of its inclusion of strokes as a ASCVD endpoint and its reliance on databases that had substantial numbers of African Americans, two major features missing from ATP III.

A risk calculator "will never be perfect, but this is a huge step ahead from where we were 12 years ago," said Dr. Donald Lloyd-Jones, professor of preventive medicine at Northwestern University in Chicago and cochair of the panel that developed the risk calculator. "We made it better for women [by including stroke as an outcome], for African Americans, and for white men, too.

We feel very confident that we are in a great place now, but as more data become available, we’re very happy to see if we can improve it further. You can certainly criticize the calculator, but I don’t know of anything that’s better," he said in an interview.

Other experts who led development of the new guidelines also stressed that they do not call for blindly prescribing a statin to every person whose risk calculates at or above 7.5%.

"No one said that patients automatically get a statin. We said that there needs to be a risk discussion between the patient and physician, because sometimes the numbers make sense and sometimes they don’t," said Dr. Neil Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University and chair of the ACC/AHA panel that wrote the new guidelines.

"For the first time, we built into the guidelines the unique judgment of physicians, and patients’ personal preferences." Risk calculation "is the start of a discussion" between a physician and patient, not the endpoint.

He also noted that the guidelines included a built-in "buffer" because "we had evidence that statins are effective even for patients with a 5% risk" for an ASCVD event over the subsequent 10 years.

The guidelines say that it is "reasonable to offer" statin treatment to a middle-age person with a 7.5% or greater 10-year risk for a ASCVD event and no other risks that warrant statin treatment and that before starting statin treatment, it is "reasonable" for a physician and patient to have a discussion that covers the patient’s individual risk level, the potential risks and benefits of statin treatment, and patient preference.

Aside from their critique of the risk calculator, Dr. Ridker and Dr. Cook applauded the overall guidelines in their commentary, calling them "a major step in the right direction."