Author + information
- Sidney C. Smith Jr., MD∗ ( and )
- Scott M. Grundy, MD, PhD
- ↵∗University of North Carolina, CB 7075, 6031 Burnett Womack, Chapel Hill, North Carolina 27599-7075
Our paper published in the August 12th issue of the Journal presents 2 points of view (1). The first author (S.C.S., Jr.) reviewed the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guideline, which places priority on statin therapy on the basis of clinical outcomes confirmed by a systematic review of randomized controlled trials. The second author (S.G.) focused on low-density lipoprotein cholesterol (LDL-C), the primary cause of atherosclerotic cardiovascular disease (ASCVD).
Dr. Dimmitt and colleagues argue for moderate-intensity statins anytime statins are indicated. They question whether high-intensity statins are worth added efficacy compared with costs and side effects. Regarding efficacy, recent meta-analysis of secondary prevention trials showed that for LDL-C “the lower, the better” for ASCVD risk reduction (2). This analysis provides justification for high-intensity statins when they can be given safely for most patients with established ASCVD. In the TNT (Treat-to-New Targets) trial, for example, atorvastatin 80 mg was tolerated as well as atorvastatin 10 mg. In TNT, incremental reduction of ASCVD events of 21% by high-dose atorvastatin compared with moderate dose cannot be called “modest.” High-intensity statins thus seem justified in most patients with established ASCVD. Unfortunately, meta-analysis (2) finds that the majority of patients treated with high-intensity statins do not achieve LDL-C in the range where still greater risk reduction could be achieved. Statins are excellent drugs but do not always maximize the potential for risk reduction inherent in LDL-C lowering therapy. New and efficacious drugs beyond statins are needed.
The letter claims that high-dose statins are not as well tolerated as moderate doses. The TNT trial did not support this contention. Dimmitt et al. overstate the harmful effects of statins. Up to 10% of patients complain of fatigue and myalgia, but clinical myopathy is rare; and rhabdomyolysis and acute renal failure are very rare. Statins may raise glucose levels in some patients, but increased microvascular disease has not been demonstrated; and macrovascular disease is reduced by statins. Cognitive dysfunction is controversial. Peripheral neuropathy is very rare. Statins do not cause chronic liver disease or chronic kidney disease.
How best to employ statins in primary prevention is an ongoing and not fully resolved issue. ACC/AHA 2013 guidelines (3) wisely recommend individualization of therapy on the basis of unbiased discussion with patients. Factors that favor statin use in primary prevention are high-risk conditions (diabetes, metabolic syndrome, chronic kidney disease, cigarette smoking, severe hypercholesterolemia, and uncontrolled hypertension). Primary prevention trials indicate “the lower, the better” for LDL-C; this is why the guidelines favor higher doses of statins. But any statin side effects are reversible when the drug is stopped. Discussion of number needed to treat to prevent ASCVD events and cardiovascular mortality can be helpful to patients for deciding whether to take a statin, and if so, at what dose. The importance of treating other risk factors should be stressed. The guidelines also recommend consideration of additional factors such as coronary artery calcium score, high-sensitivity C-reactive protein, ankle brachial index, LDL-C >160, lifetime risk estimation, and family history to further advise the patient physician discussion. Some patients may prefer lifestyle intervention instead of drug therapy. Statins should be recommended cautiously in older persons where the dangers of polypharmacy and side effects mount. Adherence to a healthy lifestyle should be a fundamental component of any therapeutic recommendations for primary or secondary prevention of atherosclerotic vascular disease.
- American College of Cardiology Foundation
- Smith S.C. Jr..,
- Grundy S.M.
- Boekholdt S.M.,
- Hovingh G.K.,
- Mora S.,
- et al.
- Stone N.J.,
- Robinson J.G.,
- Lichtenstein A.H.,
- et al.