ACC-AHA cardiovascular prevention guidelines drop cholesterol treatment goals
指南编撰委员会主席、西北大学心血管内科的Neil J. Stone博士指出，这部调脂治疗指南带来了“对LDL和非HDL胆固醇治疗目标的新视角”，确定了可将中至高强度他汀治疗作为一级或二级预防的4类患者。“尽管进行了广泛的文献复习，但我们未能找到确凿证据来支持继续使用特定的LDL-C和非HDL-C治疗目标。”
既往的指南推荐心血管高危者将LDL降至100 mg/dl以下，并建议极高危患者将LDL降至70 mg/dl或更低。
这一系列的临床实践指南最初是由国立心肺血液研究所(NHLBI)主持修订的，今年上半年改由AHA和ACC负责。ACC主席、加州大学洛杉矶分校David Geffen 医学院的John Gordon Harold博士在新闻发布会上介绍，在2011年以来的最佳临床试验和流行病学研究的基础上，除了血脂管理之外，这部“千呼万唤始出来”的指南还聚焦于评估心血管风险、改变生活方式以降低心血管风险，以及成人超重和肥胖的管理。
编撰委员会的另一位共同主席、科罗拉多大学内科学教授Robert H. Eckel博士指出，另外两项指南推荐意见分别关注了生活方式管理和超重、肥胖管理。生活方式管理指南方面推荐了心脏健康膳食模式：包括水果、蔬菜和全谷物，限制饱和脂肪、反式脂肪和钠盐摄入，并且以相应的体力活动作为膳食建议的补充。
对于能从较低血压中获益的人，新指南建议每天钠摄入量不超过2,400 mg (之前推荐美国成人每天钠摄入量不超过3,600 mg)，同时指出每天钠摄入量≤1,500 mg与更大幅度的血压降低有关。
减肥手术可以作为BMI≥35 kg/m2且有合并症的患者，或者BMI≥40 kg/m2的患者的减重选择。虽然药物治疗是一个“关键”领域，但新指南并未就药物减重提出建议，原因是在开始制定新指南时，西布曲明(已被撤市)和奥利司他是唯一在美国获准用于减肥的药物。
Ryan博士报告称与Alere Wellbeing、Amylin、Arena制药、卫材、诺和诺德、NutriSystem、Orexigen、武田和Vivus等公司有利益关系。她是Scientific Intake的首席医疗官。
By: ELIZABETH MECHCATIE, Cardiology News Digital Network
A move away from specific cholesterol treatment targets, assessment of both 10-year and lifetime cardiovascular disease risk, and inclusion of stroke in cardiovascular disease risk estimates are among the highlights of updated clinical practice guidelines on reducing cardiovascular risk released Nov. 12 by the American College of Cardiology and American Heart Association.
Written by the blood cholesterol expert panel that was originally the Adult Treatment Panel (ATP) IV, the cholesterol treatment guideline will inevitably receive the most attention, with the shift from recommending treatment of cholesterol to a specific LDL cholesterol target to treatment based on an increased risk for cardiovascular disease and stroke with medications proven to reduce those risks.
"Rather than LDL-C or non–HDL-C targets, this guideline used the intensity of statin therapy as the goal of treatment," identifying four groups of individuals "for whom an extensive body" of evidence from randomized controlled trials demonstrated a reduction in atherosclerotic CVD events "with a good margin of safety from moderate- or high-intensity statin therapy," the panel concluded.
While these guidelines are a change from previous guidelines, "clinicians have become accustomed to change when that change is consistent with the current evidence," they added.
The cholesterol treatment guideline provides "a new perspective on LDL and non-HDL treatment goals," with the identification of the four groups of patients for whom moderate- or high-intensity statin treatment is recommended, for primary or secondary prevention, explained Dr. Neil J. Stone, chair of the writing committee.
"Despite an extensive review, we were unable to find solid evidence to support continued use of specific LDL-cholesterol or non-HDL treatment targets," he said in a telephone briefing.
The previous guidelines recommended treating to an LDL goal of below 100 mg/dL in people at high cardiovascular risk, but also recommended a goal of 70 mg/dL or lower for patients at very high risk.
The four sets of clinical practice guidelines were initially commissioned by the National Heart, Lung, and Blood Institute (NHLBI) in 2008, and were transitioned to the AHA and ACC earlier this year. On the basis of evidence from the best clinical trials and epidemiologic studies through 2011, the "long-awaited" guidelines focus on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of overweight and obesity in adults, in addition to management of blood cholesterol, Dr. John Gordon Harold, ACC president, said during the briefing.
The 2013 guidelines "will provide updated guidance to primary care providers, nurses, pharmacists, and speciality medicine providers on how to best manage care of individuals at risk of cardiovascular diseases," based on evidence available through 2011, said Dr. Harold of the David Geffen School of Medicine at the University of California and Cedars-Sinai Heart Institute, Los Angeles.
In the cholesterol treatment guideline, Dr. Stone said that based on an extensive literature review, the evidence supported the use of the "appropriate intensity" of statin therapy in addition to a heart-healthy lifestyle to reduce risk, with the identification of four "major statin benefit groups" for whom "high intensity" statin treatment (lowering LDL by at least 50%) or "moderate intensity" statin treatment (lowering LDL by roughly 30%-49%) is recommended. Those groups are patients with:
· Clinical atherosclerotic cardiovascular disease (ASCVD).
· A primary elevation of LDL-cholesterol of 190 mg/dL or higher, including those with familial hypercholesterolemia.
· Diabetes, aged 40-75 years with no clinical ASCVD and LDL levels of 70-189 mg/dL.
· No clinical ASCVD or diabetes, aged 40-75 years, with an LDL of 70-189 mg/dL and an estimated 10-year risk of ASCVD of at least 7.5% (determined by calculating the global cardiovascular risk assessment score, using formulas developed by the Risk Assessment guideline work group and included in that guideline).
"The idea was that certain groups such as those with [a prior atherosclerotic event] and those with very high LDL-cholesterol, especially these familial forms ... benefit most, if they can tolerate it, from high-intensity statin therapy."
For those with a score of 7.5% or more, who have not had an MI or stroke, analyses provide strong evidence that treatment can forestall or prevent these events, and in those at high risk, "even can reduce total mortality," said Dr. Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University, Chicago.
Often, the use of a specific target might lead to undertreatment in certain groups, or overtreatment when, for example, additional medications that are not proven to add incremental or additional benefit are added to treatment. Rather than supporting a target, the data indicated that clinicians "use the appropriate intensity of statin therapy to reduce this atherosclerotic risk in those most likely to benefit," and that nonstatin therapies "didn’t provide an acceptable CVD risk reduction benefit compared to their adverse effects in the routine prevention of heart attack and stroke," Dr. Stone noted.
Assessment of cardiovascular risk
The guideline on assessing cardiovascular risk in adults includes the global risk assessment tool, which "provides a quantitative clinical assessment to guide clinical care," said Dr. Donald M. Lloyd-Jones, one of the cochairs in the work group that wrote this guideline.
The guideline recommends lifetime risk alongside 10-year risk, said Dr. Lloyd-Jones, chair and professor of preventive medicine at Northwestern University, Chicago. The 10-year risk equations predict the risk of MI and stroke, while previous risk equations focused only on the risk of coronary heart disease events. "We realized quickly that we were leaving a lot of risk on the table by not also including stroke in our risk assessment algorithm," which is particularly important in female and black patients, he said.
Estimating lifetime risk may be particularly useful for identifying younger patients who have a low 10-year risk "but who have unhealthy lifestyles or risk factors that will put them at substantial risk for developing cardiovascular disease in the longer term," he added.
The risk equations for non-Hispanic white men and women and for black men and women are based on data from NHLBI-funded population-based studies, including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Atherosclerosis Risk in Communities Study (ARIC), and the Cardiovascular Health Study (CHS), as well as the Framingham Heart Study.
These require input of age, sex, race, total and HDL cholesterol levels, blood pressure, blood pressure treatment status, and current smoking and diabetes status, which were identified as the best predictors for 10-year risk, Dr. Lloyd-Jones said.
Other risk markers were considered, but were not included because there was not sufficient information to warrant their inclusion in the equations. Until risk-predictor equations are developed for Hispanics, Latinos, and Asian-Americans, as relevant data become available, the risk equations for white men and women should be used for other races and ethnic groups in the United States, he said.
Based on review of the literature on newer risk markers, the work group determined that four markers "may be considered" in refining risk estimates, if there is uncertainty after performing the risk equations: family history of premature cardiovascular disease in a first degree relative, coronary artery calcium score, measurement of high sensitivity of C-reactive protein (CRP), and measurement of ankle-brachial index.
The evidence for using other markers was insufficient, and "we explicitly recommend against performing carotid intimal medial thickness measurement," because of evidence that there is no additional benefit of this test, Dr. Lloyd-Jones said.
The guideline provides information on how to incorporate risk assessment into clinical practice settings, and includes an Excel spreadsheet that can be used to calculate risk, said Dr. Lloyd-Jones. Risk equations can also be programmed into electronic health records.
Dr. John Rumsfeld, acting national director of cardiology for the Veterans Health Administration, views the change in cholesterol treatment recommendations as "a course correction," rather than a radical change in direction.
"These guidelines are based on an objective review of the evidence – and that evidence is clear: There is no evidence for treating to specific target numbers for cholesterol. Yet, there is clear and strong evidence for the use of statin medications for people at elevated risk for heart disease and stroke," he said.
"The new treatment approach is more patient centered; it is about treating those who are most likely to benefit from taking a chronic medication; it is about reducing their risk with proven medicines; and it also reduces patient burden by lessening the need for repeat testing and taking additional, unproven medications," he said in an interview.
Over a year ago, the VA health care system dropped its national performance measure for treating to an LDL-cholesterol below 100 mg/dL, based on an independent review of the evidence. Using an approach that is similar to that recommended in the new guideline, the VA implemented a performance measure that emphasized the use of statin medication in patients at elevated risk.
"The change from treating targets to treating risk leads to fewer patients being overtreated with unproven medications, and reduces the burden on patients of repeated blood testing and additional medications to take," said Dr. Rumsfeld, also professor of medicine at the University of Colorado, Denver. In addition, the change reduces repeat blood tests and extra medication use, reducing costs to the health care system, he pointed out.
"Instead of repeated laboratory testing, and uptitrating medications or adding additional medications for patients to take with possible side effects, this approach emphasizes initiating treatment with proven medications for those at risk," he said.
Although clinicians may be initially surprised by the guidelines, he said he believes they will be well received. Clinicians "will quickly see that the approach reflects current evidence, and that the approach simplifies care," said Dr. Rumsfeld, who served as one of the expert reviewers of the guidelines.
Lifestyle management to reduce cardiovascular risk
The other two guidelines are on lifestyle management, and on overweight and obesity. The lifestyle management guideline includes recommendations for a dietary patterns that are heart healthy, including those with fruits, vegetables, and whole grains; limiting saturated fat, trans fat, and sodium intake; and for a physical activity level that complements dietary recommendations," said Dr. Robert H. Eckel, cochair of the writing committee, and professor of medicine at the University of Colorado, Denver.
The physical activity recommendations are based largely on a 2008 Department of Health and Human Services report, which provided support for 30-40 minutes of moderate to vigorous activity at least 3-4 days a week.
For people who could benefit from a lower blood pressure, the guideline recommends a sodium intake of no more than 2,400 mg per day (a reduction from the current average of about 3,600 mg a day among U.S. adults), but points out that sodium intake of 1,500 mg a day or less has been associated with greater reductions in blood pressure.
Management of overweight and obesity in adults
The guidelines on the management of overweight and obesity in adults, developed with the Obesity Society, provide recommendations in five major areas and include a treatment algorithm on weight management, to help primary care providers address weight management in their patients, said Dr. Donna Ryan, cochair of the writing committee and professor emeritus at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.
The guidelines help primary care providers identify which patients need to lose weight and how much weight loss is needed, as well as the benefits of weight loss, the best diet, the effectiveness of lifestyle interventions, and the benefits and risks of bariatric surgery.
The recommendations include the use of body mass index as "a quick and easy first screening step" to identify patients who may be at risk for obesity-related health problems, and weight circumference as an indicator of ASCVD risk, type 2 diabetes, and all-cause mortality, Dr. Ryan said.
Since the ideal weight loss diet has not been identified, providers should recommend a diet that results in reduced caloric intake, and the type of diet "should really be determined by the patient’s preferences and their health status," such as a reduced calorie, reduced sodium diet for an overweight, hypertensive patient.
Another recommendation is a comprehensive approach to weight loss that involves diet and physical activity, with counseling for 6 months or more – which ideally should be on-site group or individual counseling sessions with a trained professional for at least 1 year.
Bariatric surgery may be an option for patients with a BMI of 35 kg/m2, with comorbidities, or a BMI of 40. Although a "critical" area, recommendations on pharmacotherapy are not included, because at the time the guidelines were being developed, sibutramine (which has since been taken off the market) and orlistat were the only medications approved for weight loss in the United States.
Dr. Stone, Dr. Lloyd-Jones, and Dr. Rumsfeld had no disclosures.
Dr. Eckel disclosed ties to Merck, Pfizer, Abbott, Amylin, Eli Lilly, Esperion, Foodminds, Johnson & Johnson, Novo Nordisk, Vivus, GlaxoSmithKline, and Sanofi-Aventis/Regeneron.
Dr. Ryan disclosed ties to Alere Wellbeing, Amylin, Arena Pharmaceuticals, Eisai, Novo Nordisk, Nutrisystem, Orexigen, Takeda, and Vivus. She is chief medical officer of Scientific Intake.