Re: Should people at low risk of cardiovascular disease take a statin?
Grundy’s Response to Abramson and Colleagues Article on Statins in Low-Risk People
Scott M. Grundy
Center for Human Nutrition and Department of Internal Medicine
UT Southwestern Medical Center
5323 Harry Hines Blvd., Suite Y3.206
Dallas, TX 75390-9052
Veterans Affairs Medical Center
Dallas, TX 75216
Abramson et al.1 recently asked whether persons at low risk for cardiovascular disease (CVD) should take statins. This is an important question because billions of people worldwide are at low risk by current standards. Abramson et al.1 give several reasons for excluding low-risk persons from statin therapy: better non-drug alternatives, lack of overall health benefit, high cost of treatment, and side effects. Unfortunately, the article does not provide an enlightened discussion of this complex issue. Although the authors state that lifestyle factors—including lack of exercise, tobacco use, and unhealthy diet--account for 80% of CVD, this is not true. These factors contribute to causal risk factors for CVD; but they only partially account for age-related rise in cholesterol and blood pressure, which contributes so much to CVD. And for several reasons, many people will not adhere to a healthy lifestyle. The statement further is made “for people at low risk of CVD (<10% risk over next five years, i.e. < 2% per year risk), statins do not reduce the overall risk of death or serious illness”. First, meta-analysis shows that statins reduce total mortality and CVD mortality in primary prevention.2 Most current guidelines stratify risk within this range, and at a minimum, recommend statins for persons in the upper half of this range (i.e. > 1% risk for CVD per year). And second, once statins are started, it is expected that they will be taken for a lifetime. The net benefit over a lifetime is far greater than what is achieved over 5 years. The authors make another point: “to prevent one heart attack or stroke, 140 low risk people (< 10% five-year risk) must receive statins for five years”. The number-needed-to-treat argument can be highly misleading. At a minimum, 140 people over 5 years translate into 70 people over 10 years, 35 people over 20 years, and still fewer over a lifetime.
Finally, the authors say “the side effects of statins--including muscle symptoms, increased risk of diabetes, decreased energy, liver inflammation, cataracts, sexual dysfunction, and exertional fatigue--occur in about 20% of people treated with statins”. There is no convincing evidence that statins cause cataracts.3 In spite of intermittent transaminase elevations, true statin hepatoxicity appears to be virtually non-existent.4 Cognitive and/or sexual dysfunction due to statins is controversial to say the least and has by no means been proved.5
The major untoward symptom of persons taking statins is muscle discomfort or fatigue. Lipidologists commonly receive referrals for patients complaining of various types of muscle pain. This discomfort is almost always subjective; objective abnormalities are rarely found. The prevalence of statin-induced muscle complaints is not well established. Careful examination of patients often reveals that symptoms are in fact due to other problems (e.g. arthritis, neuropathy, and muscle strain). The best study to date was a randomized trial comparing atorvastatin 80 mg/day vs placebo over 6 months in 420 healthy, statin-naive subjects.6 Careful evaluation showed no significant differences between the two treatment arms in several measures of muscle strength or exercise capacity. Atorvastatin-treated subjects had more myalgia than placebo (19/203 versus 10/217 cases, respectively; P=0.05). Myalgic subjects on atorvastatin or placebo showed no differences in muscle strength. From this study, it appears that atorvastatin causes a low incidence of muscle pain. But vast clinical experience indicates that statins do not cause irreversible muscle damage. Any statin-induced myalgia disappears when statins are discontinued. Statin myalgia thus is not a valid argument against use of statins. Patients with true statin myalgia are faced with a choice: try to adjust to the myalgia or give up and lose the CVD risk reduction accompanying statin therapy.
The review by Abramson et al.1 fails to make a cogent argument that statins should not be used in low-risk individuals. The question is important and deserves serious evaluation and analysis. The science underlying risk reduction at any level of CVD risk is strong. Whether this science should translate into a public policy for statin usage in low-risk subjects is a different issue and deserves serious attention at a policy level. But the dangers of statins should not be overstated. Severe side effects are exceedingly rare, and when subjective symptoms can be attributed to statins, they disappear without residuum when statins are withheld.
1. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013;347:f6123.
2. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1: CD004816
3. Klein BE, Lee KE, Klein R. Statin use and cataracts. JAMA Ophthalmol 2014;132:366-7.
4. Tolman KG. Defining patient risks from expanded preventive therapies. Am J Cardiol 2000; 85:15E-9E.
5. Richardson K, Schoen M, French B, Umscheid CA, Mitchell MD, Arnold SE, et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013;159:688-97.
6. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, et al. Effect of statins on skeletal muscle function. Circulation 2013;127:96-103.
Competing interests: No competing interests