This article covers very well controversial aspects of these new guidelines.
Guidelines are only guidelines.
Practitioners should take these new guidelines into consideration in his clinical judgement
in each individual patient. He doesn't have to adhere to them.
I believe there will be some changes in the clinical practice but not too much.
I believe the old guidelines with specific target numbers did a lot of good in spite of lack of published
concrete evidence. I said this with my own clinical experience following coronary heart disease patients
for many years up to some forty years. I have so many patients who have proved this point.
I was invited to the 102nd birthday party of one patient whom I subjected to CABG in 1975.
My patient and former dentist of mine, age 86, whose two older brothers died of CHD under my care,
and who has familial hypercholesterolemia and became my patient in his forties is still free of CHD
and is leading active life style.
I have a former school teacher who suffered an MI in his early thirties and was found to have severe mixed hyperlipidemia
with triglyceride over 1000 and cholesterol around 300. This was in 1970's.
I had him undergo partial intestinal bypass by Dr. Buckwalter at University of Minnesota as part of clinical trial
sponsored by NIH at that time. About 10 years ago I had his intestinal bypass reversed because of persisting diarrhea
and available anti lipid drugs. He is still leading active full life in his late 70's.
These are only a few examples of what tight lipid control even beyond old guideline numbers can do in preventing
and reversing CHD.
ACC-AHA cardiovascular prevention guidelines drop cholesterol treatment goals
By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network
11/12/13
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.
Lifestyle management was among the areas highlighted in new clinical practice guidelines on reducing cardiovascular risk recently released by the American College of Cardiology and the American Heart Association.
"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.
Cholesterol treatment
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:
• 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.
Dr. Donald Lloyd-Jones
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.
Steven L. Zweibel has been taking a statin drug to lower his cholesterol for seven years. It has worked, and he has suffered no problems or side effects.
But, like many patients taking these drugs, he is perplexed by new guidelines on preventing heart disease and stroke despite the fact that he is the director of cardiac electrophysiology at Hartford Hospital.
“I am very happy to be on Zocor,” said Dr. Zweibel, 47, referring to the statin he takes. “But now the real question in my head is whether I need to be on it.”
The new guidelines, released on Tuesday by the American College of Cardiology and the American Heart Association, represent a remarkable and sudden departure from decades of advice on preventing cardiovascular disease.
According to the new advice, doctors should not put most people on cholesterol-lowering medications like statins based on cholesterol levels alone. And, despite decades of being urged to do so, patients need not monitor their cholesterol once they start taking medication. The guidelines do not even set target levels for LDL, the so-called bad cholesterol.
Doctors are also being told to stop adding other cholesterol-lowering drugs to statins, because those drugs have not been proved to reduce the risk of heart attacks and strokes.
For patients and doctors alike, all of this amounts to a surprising, and at times baffling, change in perspective.
The guidelines tell doctors and patients to use a new online risk calculator to determine whether they need treatment. Some patients, like Nancy Hayward, 60, of Sacramento, who started taking a statin in 2007 because her LDL was mildly elevated, do not qualify because they have no other risk factors for heart trouble.
Dr. Zweibel would like to use the calculator to assess his own risk of heart attack or stroke. But it requires a person’s baseline cholesterol measurement, and Dr. Zweibel has no idea what his is without the statin.
He could, and says he probably will, stop taking the drug for a couple of months and then have his cholesterol measured. But what then? Should he stop taking the drug if the calculator says his 10-year risk of a heart attack or stroke is less than 7.5 percent, the new cutoff point for treatment?
He worries about letting his cholesterol drift up. There is dementia in his family, and cardiovascular risk factors are also risk factors for dementia.
“I wonder if Zocor could help” prevent dementia, he said. “It’s a very tough decision.”
By taking a statin diligently, Roland Paul, a 76-year-old corporate lawyer in Greenwich, Conn., managed to reduce his LDL level to an almost unheard-of 55 milligrams per deciliter, a feat of which he is proud. “My doctor thought it was gangbusters,” Mr. Paul said.
But the guidelines committee now says there is no evidence that he is better off with that number than with a higher one. Mr. Paul said he was no longer as concerned about keeping his cholesterol so low.
The new approach poses challenges to clinicians, too. Doctors often use LDL levels as motivators to keep patients on statins. Many expect that the task will be more difficult without regular monitoring.
Dr. Barron H. Lerner, an internist and professor of medicine at New York University, gives patients a printout with their LDL levels circled before and after they start taking statins.
“It is really helpful to have some kind of results to show people,” Dr. Lerner said. “I will predict 100 percent that I will have some patients who say, ‘If you are not going to check the LDL level and you cannot tell me the statin is working, then I am not going to take it.’ ”
Monitoring LDL levels has been an ingrained part of preventing heart attacks for decades.
“The terminology that keeps coming to mind is ‘leap of faith,’ ” Dr. Lerner said. “You have to trust your doctor and the people who did the studies that they are correct that you don’t have to check LDL levels.”
Patients and doctors striving for low numbers are now being told that they should regard taking a statin as they might regard taking aspirin to reduce their heart attack risk: a pill a day, with no monitoring required. This advice has left some cardiologists wondering what to do about patients who are at high risk but cannot tolerate statins or refuse to take them.
“Clearly, the focus is to get people on statins,” said Dr. Christie Mitchell Ballantyne, the chief of cardiology and cardiovascular research at Baylor College of Medicine, in Houston. “But if someone has seen four doctors and tried six statins and tells me they can’t take them, what am I going to do? Tell them they are a failure?”
Dr. Ballantyne said he would give such patients a nonstatin drug, despite the guidelines.
Still, some doctors agree that cholesterol targets have been too much of a fixation. Many people, both doctors and patients, have lost sight of the fact that the goal is to reduce the risk of heart disease, not just LDL levels, said Dr. Steven Woloshin, an internist at Dartmouth.
“If you ask patients, ‘Why do you take a statin?’ ” Dr. Woloshin said, “they say ‘to lower my cholesterol level,’ not ‘to lower my cardiovascular risk.’ ”
Statins do more than just lower cholesterol, noted Dr. Valentin Fuster, director of the heart center at Mount Sinai Hospital in New York City. They also reduce inflammation and blood clotting, both of which are associated with heart attack and stroke risk. Drugs that only reduce LDL have not been shown to be effective in preventing heart attacks.
It is uncertain how much of statins’ effectiveness can be attributed solely to their cholesterol-lowering properties. “Maybe we got lucky with statins,” said Dr. Harlan M. Krumholz, a cardiologist at Yale.
The chairman of the committee that developed the new guidelines, Dr. Neil J. Stone of Northwestern University, said the group was prompted to examine the idea of target LDL levels when two doctors Dr. Krumholz and Dr. Rodney A. Hayward of the University of Michigan asked what the evidence was for their efficacy.
When the committee looked, Dr. Stone said, they found no evidence. It was generally accepted that lower was better, but no one had shown that an LDL of 90 milligrams per deciliter, for example, was better than 100. And the high doses and multiple drugs many patients were taking to get to target levels raised concerns.
Dr. Lisa Schwartz, a professor of medicine at Dartmouth, said that medical systems constantly prodded doctors to report patients’ LDL levels and used the numbers to judge doctors’ performance. Referring cardiologists often insist that LDL levels be measured and then lowered.
“Everyone adopted the targets,” Dr. Schwartz said. “It drove a huge amount of testing and focusing around the LDL number. Many doctors thought it was crazy. We were prescribing higher doses of drugs for older patients, which was probably dangerous
(The above story is by Gina Kolata under the heading, " The New Cholesterol Advice Startles Some Doctors, NY Timess, Nov 13, 2013)
I sympathize with Dr. Zweibel's dilemma.
Personally I believe that vascular dementia is preventable by the tight control of the lipids, especially LDL cholesterol.
There are many elderly people with brain atrophy with so-called small vessel ischemic disease, frequently reported
by the radiologists on their reports of MRI of the brain. Their family docs often would tell them your brains are normal
for your age. According to one review article in Mayo Clinic Proceedings sometime ago, this is often the background of
the vascular dementia we may be able to prevent. These people don't necessarily develop classic strokes of any kinds.
This is what Dr. Zweibel is concerned about, I believe.
I have seen this kind of cases often in my practice, and clinicians have to use his informed judgements in each case
as far as the use of the statins are concerned.
Guidelines are only guidelines as I stated.
Guideline authors, AHA-ACC leaders confident in risk calculator
By: MITCHEL L. ZOLER, Internal Medicine News Digital Network
11/19/13
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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.
Mitchel L. Zoler/IMNG Medical Media
Dr. Donald Lloyd-Jones
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%.
Mitchel L. Zoler/IMNG Medical Media
Dr. Neil Stone
"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."
Accumulating Evidence for Statins in Primary Prevention FREE ONLINE FIRST
Jennifer G. Robinson, MD, MPH1,2,3
[+] Author Affiliations
JAMA. Published online November 25, 2013. doi:10.1001/jama.2013.281355 Text Size: A A A
Article
References
Many voices in the public and the medical community argue strongly against the widespread use of statins for the primary prevention of atherosclerotic cardiovascular disease. Critics give several reasons to avoid statin therapy, including concerns about adverse effects, lack of a total mortality benefit, cost, and a philosophical aversion to drug therapy. However, the passage of time has allowed sufficient evidence to accumulate to refute each of these concerns.
Meta-analyses now provide extensive evidence that statins reduce cardiovascular events and total mortality in individuals at lower risk of cardiovascular events than has previously been appreciated, and do so with an excellent margin of safety.1- 3 In this issue of JAMA, Taylor and colleagues4 provide a summary of the 2013 Cochrane2 meta-analysis (an updated version of the 2011 Cochrane meta-analysis on this topic3) of 18 primary prevention statin trials including 56 934 participants. The authors report that statins significantly reduce all-cause mortality (−14%), fatal and nonfatal cardiovascular disease (−22%), coronary heart disease (−27%), stroke (−22%), and coronary revascularization (−38%). These risk reduction benefits occurred in the absence of an increased risk of cancer, myalgia, rhabdomyolysis, liver enzyme elevation, renal dysfunction, or arthritis.
Importantly, participants treated with statins were no more likely to discontinue treatment than the placebo group (12%). This means that the adverse event rates were similar in both statin and placebo/control groups, and not just an artifact of those with adverse effects who stopped the statin. Only new-onset diabetes was observed to occur frequently in the statin group, consistent with another meta-analysis of statin trials.5
The 2013 Cochrane meta-analysis was reviewed as part of the evidence-base for the recently released 2013 American College of Cardiology and American Heart Association guideline on the treatment of blood cholesterol to prevent atherosclerotic cardiovascular disease in adults.6 The 2013 cholesterol guideline was the result of a rigorous systematic review of higher-quality randomized trials, and systematic reviews and meta-analyses of randomized trials of drug therapy to reduce atherosclerotic cardiovascular disease events. The 2010 and 2012 Cholesterol Treatment Trialists (CTT) individual-level meta-analyses of statin trials and the individual primary prevention trials were also included in the guideline evidence review.7 The guideline recommends moderate- or high-intensity statin therapy for the primary prevention of atherosclerotic cardiovascular disease in individuals with 7.5% or greater 10-year atherosclerotic cardiovascular disease risk based on strong evidence that the reduction in atherosclerotic cardiovascular disease events outweighs the potential for adverse effects (including new-onset diabetes).6 Moderate-intensity statin therapy can be considered in individuals with 5% to lower than 7.5% 10-year atherosclerotic cardiovascular disease risk. These cut points are indeed lower than were recommended in the Adult Treatment Panel III update8 and are consistent with the findings in the 2013 Cochrane meta-analysis.
Notably, the 2013 cholesterol guideline cut points were derived from the placebo rates for myocardial infarction, stroke, and cardiovascular disease death observed in the 3 exclusively primary prevention statin trials, Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) study, and the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER).9- 11 Subsequent to the initial development of the 2013 cholesterol guideline primary prevention recommendations, the 2012 CTT individual-level meta-analysis confirmed the reduction in cardiovascular disease events, as well as in total mortality, from statin therapy used in low-risk individuals.1 Indeed, the 2012 CTT meta-analysis found a greater reduction in the relative risk of major cardiovascular disease events (including revascularizations) in those with a lower than 10% 5-year risk than in those with 10% or higher 5-year risk.
To guide the decision to initiate a statin for primary prevention, the 2013 cholesterol guideline used estimated 10-year atherosclerotic cardiovascular disease risk (defined as the first of “hard” events of nonfatal myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke, not including revascularization).6 Rates of revascularization are roughly equivalent to the rates of myocardial infarction and stroke,7 so the guideline cut points of 7.5% and 5% 10-year atherosclerotic cardiovascular disease risk roughly correspond to 15% and 10% 10-year combined event rates (including revascularizations), respectively, in the 2013 Cochrane evidence synopsis.4
In contrast to the 2013 Cochrane trial-level meta-analysis of 18 primary prevention trials, the CTT individual-level meta-analysis of 28 primary and secondary prevention statin trials did find a very slightly increased risk of serious myopathy, rhabdomyolysis, and hemorrhagic stroke in statin-treated individuals.1 These findings do not alter the atherosclerotic cardiovascular disease benefit-adverse effect considerations used for the 2013 cholesterol guideline primary prevention recommendations.5 The guideline further notes muscle complaints are common in patients who are treated, as well as those who are untreated, and it is difficult to determine whether those symptoms are related to statin treatment without a rechallenge. Thus, a management algorithm for muscle symptoms in patients who are treated with statins has been provided.
Another meta-analysis of statin trials found the rate of excess new-onset diabetes to be dose-related,12 an issue not addressed in this Clinical Review. However, whether the slight excess of statin-associated diabetes has long-term adverse effects is unclear. A 2012 analysis of the JUPITER trial found that new-onset diabetes was diagnosed on average 6 weeks earlier in the rosuvastatin-treated (20 mg) group than in the placebo group, and limited to those with diabetes risk factors.13 There were 2.5 cardiovascular disease events or deaths avoided for each excess case of diabetes in the rosuvastatin-treated group. While more research is needed, these findings are reassuring regarding the safety and efficacy of statins in lower-risk primary prevention.
The most recent meta-analyses of statin trials that provide extensive evidence of statins reducing cardiovascular disease events and all-cause death when used for primary prevention with an excellent margin of safety were performed in individuals selected for likelihood of benefit and safe participation.1,2 Although cardiovascular disease risk factors were present, these were healthy individuals aged 40 to 75 years, without serious comorbidities and who were not taking drugs with the potential for statin interaction. Few participants were older than 75 years. Therefore, healthy individuals similar to those who participated in the statin trials that found a cardiovascular disease risk-reduction benefit should be the focus of statin treatment for the primary prevention of cardiovascular disease. However, statins did not reduce cardiovascular disease events in trials performed in populations with heart failure or receiving maintenance hemodialysis.6 Whether statins would have similar efficacy and safety in individuals who would not have been eligible to participate in the clinical trials is unknown.
In sum, the recent statin meta-analyses provide evidence that largely refutes the major criticisms against statins used for primary prevention. Statins are well tolerated in properly selected individuals. Statins reduce total mortality as well as atherosclerotic cardiovascular disease events in lower-risk individuals. Concerns about cost are no longer relevant with 5 of the currently available statins available as generic drugs. Indeed, recent analyses have found statins to be highly cost-effective and even cost-saving in lower-risk individuals, and can provide a large societal benefit.14,15 The accumulated evidence should convince those with a philosophical aversion to statin therapy for primary prevention to reconsider their stance. Despite decades of exhortation for improvement, the high prevalence of poor lifestyle behaviors leading to elevated cardiovascular disease risk factors persists, with myocardial infarction and stroke remaining the leading causes of death in the United States.16 Clearly, many more adults could benefit from evidence-directed use of statins for primary prevention.
ARTICLE INFORMATION
ARTICLE INFORMATION | REFERENCES
Corresponding Author: Jennifer G. Robinson, MD, MPH, Department of Epidemiology, College of Public Health, University of Iowa, 105 River St, S455, CPBH, Iowa City, IA 52242 (jennifer-g-robinson@uiowa.edu).
Published Online: November 25, 2013. doi:10.1001/jama.2013.281355.
Conflict of Interest Disclosures: Dr Robinson has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. She reports receiving grants to her institution from Amarin, Amgen, AstraZeneca, Daichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Regeneron, Roche, sanofi-aventis, and Takeda; and consulting for Amgen, Pfizer, and sanofi-aventis.
Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.
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Guidelines are only guidelines.
Practitioners should take these new guidelines into consideration in his clinical judgement
in each individual patient. He doesn't have to adhere to them.
I believe there will be some changes in the clinical practice but not too much.
I believe the old guidelines with specific target numbers did a lot of good in spite of lack of published
concrete evidence. I said this with my own clinical experience following coronary heart disease patients
for many years up to some forty years. I have so many patients who have proved this point.
I was invited to the 102nd birthday party of one patient whom I subjected to CABG in 1975.
My patient and former dentist of mine, age 86, whose two older brothers died of CHD under my care,
and who has familial hypercholesterolemia and became my patient in his forties is still free of CHD
and is leading active life style.
I have a former school teacher who suffered an MI in his early thirties and was found to have severe mixed hyperlipidemia
with triglyceride over 1000 and cholesterol around 300. This was in 1970's.
I had him undergo partial intestinal bypass by Dr. Buckwalter at University of Minnesota as part of clinical trial
sponsored by NIH at that time. About 10 years ago I had his intestinal bypass reversed because of persisting diarrhea
and available anti lipid drugs. He is still leading active full life in his late 70's.
These are only a few examples of what tight lipid control even beyond old guideline numbers can do in preventing
and reversing CHD.