2/8/17: NATIONAL HEART MONTH: Statin Therapy; Should You Take Cholesterol-Lowering Drug If You Have No History of Cardiovascular Disease?

When the first statin drug broke through to the U.S. consumer market in the late 1980s, it was viewed as revolutionary, a potential magic bullet for the prevention and treatment of atherosclerosis, which underlies much of cardiovascular disease.

Statins, such as today’s atorvastatin (Lipitor®) and simvastatin (Zocor®), lower blood-levels of cholesterol, most notably, the low-density lipoprotein (LDL) cholesterol that we know as “bad.” High-density lipoprotein (HDL) cholesterol, which we call “good,” picks up excess cholesterol in the bloodstream and takes it to the liver, where it’s broken down. The main constituent of the plaque that builds up in the walls of our arteries, causing the scourge of atherosclerosis, is cholesterol. (For a review of atherosclerosis, see my 2/1/17 blog.)

Cholesterol is a lipid; a lipid is a fat. Our bodies’ cells are made up principally of lipids, carbohydrates, and proteins. Our bodies—chiefly, our livers—make all of the cholesterol we need, but we get more of this lipid when we eat foods from animal sources that are high in saturated and trans fats.

Recently, the question has arisen as to whether healthy people who have no history of cardiovascular disease (CVD), but who are at an increased risk of developing CVD, should take a statin for primary prevention, before disease occurs. Last November, the U.S. Preventive Services Task Force (USPSTF) issued new recommendations for the use of statins as preventive medications, thus replacing its 2008 recommendations about screening for lipid disorders in adults. This independent panel of medical authorities opened the door wider for expanded statin therapy.

If people with normal cholesterol levels can take a statin and potentially prevent cardiovascular disease from occurring, should they?

***

Background

“Statins are a class of lipid-lowering medications that function by inhibiting [an] enzyme [that is involved in] the production of cholesterol,” the USPSTF explained in an article about its recommendations that was published in the Nov. 15, 2016 issue of the Journal of the American Medical Assn.

This enzyme is 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, which you’ll see abbreviated as HMG CoA reductase.

“Statins reduce levels of total cholesterol and LDL-C and, to a lesser extent, triglycerides,” the USPSTF continued, “and probably have anti-inflammatory and plaque stabilization effects as well.”

Today, according to the task force, almost 28 percent of Americans age 40 and older, or about 40 million people, take a statin to protect them against microcardial infarctions (heart attacks) and strokes brought on by atherosclerosis. Nearly half of all adults 75 and older in the United States use a prescription cholesterol-lowering medication; 80 percent of them use a statin alone.

Twenty-five years after the FDA approved Merck’s 1980s breakthrough drug, lovastatin, an estimated 375,000 adults in the United States still die each year of coronary artery disease and 130,000 die of cerebrovascular disease (strokes). According to the USPSTF, cardiovascular disease causes one of every three deaths among adults in the United States.

What happened to the magic bullet?

***

Expansion of statin use

One thing that happened was experience. With statin use among millions of people, painful and, in rare circumstances, life-threatening adverse effects, occurred. The downside of the cholesterol-lowering medication popped up. (All drugs have multiple effects. I refer to adverse effects, not side effects.)

Initially, lovastatin was recommended for people who already had cardiovascular disease or very high LDL or total cholesterol levels. Over time, as the evidence of statins’ effectiveness accumulated, physicians began to prescribe them for patients who had only moderately elevated cholesterol, but who might benefit from the enzyme-inhibiting drug. Since all drugs pose risks, these were people perceived as having more to gain than to lose from statin use—notably, people with moderately-high cholesterol and other CVD risk factors, such as a family history of early cardiovascular disease or a personal history of smoking.

Muscle pain, aka myalgia, is the adverse effect most commonly cited with statins. The muscle soreness and weakness may be mildly uncomfortable or quite severe. In rare cases, statin-associated muscle damage can threaten vital organs, including the liver. How much pain a statin-using patient may experience or is willing to tolerate obviously depends on the individual and his/her health circumstances. Other adverse effects reportedly associated with statins include type-2 diabetes and cognitive impairment. (See below.)

In every patient decision to take a statin, it is smart and pertinent to ask whether the potential benefits outweigh the potential risks.

***

Task Force Recommendations

In its new recommendations, the USPSTF concludes with “moderate certainty” that “initiating use of low- to moderate-dose statins for the prevention of CVD events and mortality in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors . . . and a calculated 10-year CVD event risk of 10% of greater has at least a moderate net benefit.”

The USPSTF, therefore, frames the benefit-risk decision principally in terms of an individual patient’s CVD risk factors and 10-year CVD risk. That the task force no longer considers dyslipidemia—a lipid disorder, such as high LDL cholesterol—a prerequisite condition for statin use is just one of the many points medical experts have been debating since the new recommendations were released.

Experts also dispute the evidence upon which the USPSTF relied, calling the data weak, inconclusive, and/or biased, because most of the 19 studies it used were funded by statin manufacturers. They further charge that the task force underappreciated the occurrence rate and severity of adverse effects. But most critics, a number of whom contributed editorials to the Nov. 15, 2016 JAMA, seem to support the concept of primary prevention with statins, even though they don’t agree on its implementation.

The USPSTF, which is comprised of primary-care physicians and epidemiologists who are appointed and funded by an agency of the U.S. Dept. of Health and Human Services, assigns letter grades to its recommendations. With preventive statin use, it gave:

1)      A B recommendation to starting low- to moderate-dose statins in adults ages 40 to 75 who have no history of cardiovascular disease, but who have one or more CVD risk factors and a 10-year CVD risk of 10 percent or greater. (A “B” indicates moderate certainty that statin use by people in this group will have at least a moderate net benefit. Statin use will reduce the probability of an MI or an ischemic stroke by at least a moderate amount.)

2)      A C recommendation to starting low- to moderate-dose statins in adults ages 40 to 75 who have no history of cardiovascular disease, but who have one or more CVD risk factors and a 10-year CVD risk of 7.5 percent to 10 percent. (This grade is lower because the net benefit to people in this group is small. The probability of disease in this group, without drug intervention, is lower than the first group; and uncertainty exists in individual risk prediction.)

3)      An I recommendation—essentially no recommendation—to starting low- or moderate-dose statins in adults 76 years old and older who have no history of cardiovascular disease because the data for this age group are insufficient to assess the balance of benefits and harms. (Experts worry that statin-induced muscle pain and weakness may cause dangerous falls, and that the interaction of statins with other drugs commonly taken by older patients, such as anticoagulants, may exacerbate adverse effects. There also may be a point at which it is too late for statin therapy.) 

The USPSTF recognized four CVD risk factors: dyslipidemia, diabetes, hypertension, and smoking. 

It defined dyslipidemia as an LDL-cholesterol level greater than 130 mg/dL or a HDL cholesterol level less than 40 mg/dL. (Some statins, including Zocor and Crestor® (rosuvastatin), have been shown to increase blood levels of the good HDL.)

People who have LDL-cholesterol levels greater than 190 mg/dL or known familial hypercholesterolemia are not candidates for primary prevention intervention. They likely require statin use. 

Hypertension (high-blood pressure) is generally considered to be blood pressure above 140/90 mm Hg.

***

10-Year CVD Risk

The USPSTF prominently relies upon a patient’s 10-year risk of CVD as a threshold indicator for deciding if he or she is a candidate for statin therapy. To calculate that risk, it turns to the 2013 American College of Cardiology/American Heart Assn. (ACC/AHA) guidelines on the assessment of cardiovascular risk.

I first discussed the ACC/AHA risk calculation in an April 30, 2016 “tidbit” on this website and reviewed it in my July 24, 2016 blog, “To Take or Not to Take: Aspirin in the Primary Prevention of Cardiovascular Disease & Cancer.” I also mentioned it in my blog last week.

The ACC/AHA’s 10-year risk calculation takes into account your sex, age, total and HDL cholesterol levels, systolic blood pressure (the upper number of a BP reading, when the heart is contracting), and smoking habits. You can calculate your own 10-year CVD risk here:

http://www.cvriskcalculator.com/

Or use the Mayo Clinic’s calculation tool, which delves into more CVD risk factors at:

http://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease-risk/itt-20084942

I filled in information on both tools and came up with the same 10-year risk on each.

Although the USPSTF endorses the ACC/AHA tool in its recommendation statement, it also cautions that the tool has been shown to overestimate actual risk. Regardless, the task force concludes that a risk score of greater than 10 percent is a strong indicator that a statin would help.

Because of the overestimation-of-risk problem, some clinicians, such as Drs. Ann Marie Navar and Eric Peterson at Duke, insist that the critical factor in both risk assessment and treatment is and should be cholesterol level, not 10-year CVD risk. These same clinicians argue in favor of statins in younger patients, calling it reasonable to offer this therapy to those under 40 “before the benefits are fully confirmed.”

*** 

Possible Harms

If you think you might benefit from taking a statin, talk over this treatment decision with your physician. The two of you can do a benefit-risk analysis together. Your benefits will be individualized and contingent on the risk factors present. Once you have a good sense of your potential gains, you’ll want to consider statin-associated adverse effects. Unfortunately, the data on these harms are not clear-cut.

Besides myalgias (muscle aches and pains) and other muscle-related symptoms, including myopathy, possible statin-associated adverse effects include diabetes, hemorrhagic stroke, decreased cognition (loss of memory, confusion), tendon rupture, interstitial lung diseases, liver injury, and cataracts. In the clinical studies it reviewed, the USPSTF found no clear and/or convincing association between any of these effects and the implementation of low- and moderate-dose statins. But that doesn’t mean that an association does not exist.

In a seminar about statins that I attended at Johns Hopkins, I heard many anecdotal accounts of statin-induced muscle pain in the extremities—pain severe enough to terminate therapy.

Among the critics of the USPSTF’s new recommendations, Dr. Rita Redberg of the University of California-San Francisco and Mitchell Katz of the L.A. Dept. of Health believe that the task force underestimated the true risk of statins because data about the harms these drugs cause was not systematically or rigorously collected in the randomized clinical trials that the task force reviewed.

Redberg and Katz estimate the rate of muscle pain to be as high as 20 percent among patients “in the real world.” This rate reflects the experience of clinicians who see patients who are taking statins, they write in a Nov. 15, 2016 JAMA article, “Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak.”

When you consult your physician, keep in mind that you can primarily prevent future CVD with lifestyle modifications, such as eating a heart-healthy diet, getting regular aerobic exercise, maintaining a desirable body weight, and avoiding tobacco use. In fact, critics of the USPSTF’s recommendations cite research suggesting that statin users are more likely to become obese and more sedentary than nonstatin users because they mistakenly believe that taking a statin replaces the need for exercise and a good diet.

Anyone taking a statin should also be exercising and eating well.

I encourage you to look at the evidence that the USPSTF considered. You’ll find the USPSTF’s full recommendation statement in the Nov. 15, 2016 issue of JAMA, which you can access free at:

http://jamanetwork.com/journals/jama/fullarticle/2584058

I also refer you to the Mayo Clinic’s discussion of adverse effects from statin use:

http://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/statin-side-effects/art-20046013

Next up: The aging heart

SPECIAL NOTE: During National Heart Month, my publisher is offering a discount on my book, “Our Parents in Crisis: Confronting Medical Errors, Ageist Doctors, and Other Healthcare Failings,” to my Facebook readers. An autographed copy of my book is selling for $20, marked down from $27.95, and shipping is free. Please click on the Facebook link on the Improbable Books website at http://improbablebooks.com/parents.html, if you’d like to take advantage of the offer. Thank you.

Ann, 2/8/17

 

statinisland

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