HEARTBEATA Publication of South Jersey Heart Group

February 2019

in most current guidelines, and that the level of risk at which net benefit occurs varies considerably by age, sex and statin type.

The model suggests using higher 10-year risk thresholds and consideration of sex, age and statintype could markedly improve selection of persons suitable for statin therapy for primary CVD prevention, especially in the elderly because the calculator is heavily weighted toward age. Comment: I personally don’t feel that ”fake news and ageism” should restrict our use of statins in the elderly. I’m at higher risk.

Benefits of Statins Far Outweigh Risks

CVD is common and the potential benefit of lipid-lowering therapy is high. The number of patientsneeded to treat to prevent an event over five yearsvaries by baseline risk and magnitude of LDL-C reduction, from less than 10 for high-risk CVD patients receiving high-intensity therapy, to about 100 for intermediate-risk patients taking moderate-intensity statins for primary prevention.4,5 The benefits of statins in reducing the odds of heart attacks and strokes far outweigh any risks of side effects, according to a scientific statement just released by the American Heart Association (AHA) in the journal Atherosclerosis, Thrombosis and Vascular Biology. 6

The safety of statins is a very controversial topic frequently exploited by statin skeptics to convince patients not to start or to stop statins. This updated review/scientific statement provides clinicians with

Sorting Through “Fake News” to Improve Patient Outcomes

With all the unrestricted news available via the internetand social media on our phones and computers, it’sdifficult to determine what to believe, i.e., what’s true or factual and what’s “fake news.” Our Heartbeatnewsletter is dedicated to improving outcomes by disseminating the latest cardiology information basedon randomized clinical trials and/or expert opinion.

Statin Tx ”Hampered” by Clinician Beliefs

Clinicians’ personal beliefs about the safety and efficacy of statins play a larger role in their likelihoodof prescribing the medications than their knowledge of cholesterol guidelines.1 Clinically, this translates to large groups of patients receiving suboptimal care, for primary and secondary prevention of cardiovascular disease (CVD).

Are Statin Use and Harm Underestimated?

Some critics and skeptics arguethat the recent cholesterol guidelines2 emphasize the benefits of statins for CVD, but fail to take into account the full array of potential

harms.3 Findings inthis modeling study

suggest thatstatins providenet benefits athigher 10-yearrisks for CVD than

are reflected

an in-depth overview on reported safety as well as tolerability issues as reported in the large randomizedstatin trials, as well as observational cohort studies.

The most serious complications remain rhabdomyolysisand hepatotoxicity, which are observed rarely, lessthan 0.1 percent (one in 1,000) and approximately0.001 percent (one in 100,000), respectively. Myopathy,without CK elevations, was observed in less than 1percent of patients, and in less than 0.1 percent of patients that stopped their statin because of muscle-related complaints. Most muscle aches and pains inpeople taking statins are not serious and are not necessarily caused by statins. These symptoms aremore likely to be statin related if they affect both sides of the body and the thigh and shoulder musclesand occur within the first few weeks or months ofstarting treatment.

Newly diagnosed T2DM is associated with statin use,approximately 0.2 percent per year of treatment, but the presence of very common pre-diabetic characteristics (primarily obesity and sedentary activity), increases this risk. The benefit of statins still outweighs the risk.

The risk of developing a hemorrhagic stroke in patients with cerebrovascular disease is small andremains controversial. The observed reduced CVD risk in patients using statins clearly outweighs thebleeding risk—remembering that each 38.7 mg/dL lowering of LDL-C is associated with an approximately 22 percent lowering of a major adverse CV event. The authors found no evidence that statin use could increase the odds for cancer, cataracts, cognitive decline, peripheral neuropathy, erectile dysfunction or tendonitis. Comment: I think this is a great reference to defendstatin use and feel that it’s remarkable that no new or serious safety and/or tolerability issues surfaced in this updated review.

Individualized Shared Decision-Making

The degree of benefit with statins is directly related

to risk. Statins are most beneficial for high-risk

secondary prevention patients. Two groups of primary

prevention patients retain a recommendation for

statin therapy regardless of baseline estimated risk:

those with primary hypercholesterolemia whose

LDL-C is 190 mg/dL or more (high intensity) and

patients with diabetes having an LDL-C ≥70 mg/dL

(moderate intensity. Among those with diabetes,

10-year CAD risk ≥7.5 percent is an indication to consider high-intensity statin therapy.

The controversy is for primary prevention in all otherpatients aged 40 to 75 years. The decision whether to use statin therapy in primary prevention should be made after a detailed clinician-patient risk discussion. The decision to actively treat lipids with statins is largelybased on risk estimated from the ACC/AHA Pooled Cohort Equations CV Risk Calculator (Qx Calculateapp on your phone)–for those with accessed 10-yearCAD risk of five to 20 percent.

In a study of almost 14,000 patients without baselineCVD, the presence and severity of coronary artery calcium (CAC) identified patients most likely to benefit from statins for the primary prevention of CVD.7 This important study details the value of CACscoring (a 2A recommendation in the 2018 guideline)to improve accuracy of risk scoring to determine when to start statins. The central illustration is quite revealing.

Power of Zero:With the CAC score of zero, risk is

nil and those patients don’t need statins. When the

CAC score goes over 100, CV risk increases. The

number needed to treat to prevent one CV event over

the nine years decreases to 12, and these patients

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should be on statins. The reclassification potential

attributable to CAC scores is most helpful in

intermediate-risk patients with CAC scores of 7.5 to

20 percent to downgrade risk and in borderline-risk

patients with CAC scores of 100 or higher (or CAC

scores greater than 0 for age ≥55 years) to upgrade risk.

Take home for the clinician: Statins are safe and comewith lots of CV benefit. I follow the guidelines and

usually treat if the 10-year CAD risk estimate is greater

than 7.5 percent. Will I over treat in some? Yes, but

generic statins are beneficial, safe and cheap. I use

CAC scoring for those above 5 percent (borderline risk)

and family history, smoking history or metabolic

syndrome looking for a reason to treat. I use CAC

scoring to help me convince unwilling patients and

as a tiebreaker to improve accuracy of when to treat.

Because everyone over age 65 is in the high-risk

category, I like to use CAC scoring as a de-risking

approach in the otherwise healthy elderly so that

I can safely omit statin therapy. CAC scoring (not

covered by insurance) is available at South Jersey

Radiology for $129 and Our Lady of Lourdes Medical

Center and LourdesCare at Cherry Hill for $150.

Never Too Old for StatinsOlder patients are often undertreated because of perceived doubt about benefits and concern about potential increased risks of statin therapy. By combining data from all relevant trials, data show aclear benefit in the older age group.8 There is a veryslight diminution of the relative benefit of statins onvascular events in the elderly compared with youngerage groups, but the absolute benefits are often greaterin the elderly as the risk of vascular death is greater.

This meta-analysis, which summarizes evidence from28 randomized controlled trials including 186,854 patients, 14,483 (8 percent) of which were over aged75 years, showed that statin or more intensive therapyyielded a 24 percent proportional reduction in majorcoronary events per 38.7mg/dL reduction in LDL cholesterol (RR, 0.76).

The reduction was also linked to a 25 percent proportional reduction in the risk of coronary revascularization procedures and proportional reductions in stroke of any type (RR, 0.84). These benefits did not differ significantly across age groups.

The researchers report that their results show smallerproportional risk reductions in those with no knownvascular disease (the primary prevention population)compared with those with established vascular disease(the secondary prevention population). There wasmore limited evidence in the primary prevention context, but given the clear evidence overall that therelative benefits were similar irrespective of age andthe consistency of the effects at all ages in primary prevention, it is reasonable to infer that statins arelikely to be effective for primary prevention in thoseaged over 75. But more evidence is necessary for definitive conclusions.

The authors also comment that there has been a lot of misinformation about side effects. Much of thisconfusion arises from potentially biased observationalstudies, which are not able to provide reliable information. Although the absolute risks of these adverse effects are higher in the elderly, so too are the absolute risks of vascular disease, so the overallbalance of benefit and risk is still heavily weighted towardsbenefit in those aged over 75. The randomized trial evidence, which is unbiased, should be the sole source of information that we trust to guide practice.

Mario L. Maiese, DO, FACC, FACOI

Clinical Associate Professor of Medicine, Rowan SOM

Email: maiese1@comcast.net

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References

1 Lowenstern A, Navar AM, et al. Association of Clinician Knowledge and Statin Beliefs With Statin Therapy Use and Lipid Levels (A Survey of US Practice in the PALM Registry). Amer J Cardiol published online January 4 2019; DOI: https://doi.org/10.1016/j.amjcard.2018.12.031.

2 Grundy SM, Stone NJ, et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. A Report of the American College of Cardiology/American Heart Association Task Force onClinical Practice Guidelines. Journal of the American College of Cardiology. November 2018 DOI: 10.1016/j.jacc.2018.11.003.

3 Yebyo HG, Aschmann HE, Puhan MA. Finding the balance between benefits and harms when using statins for primary prevention of cardiovascular disease: a modeling study. Ann Intern Med. Published online December 4, 2018. http://annals.org/aim/article-abstract/2717730/finding-balance-between-benefits-harms-when-using-statins-primary-prevention.

4 Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality. Circulation. 2014; 130: 546-553.

5 Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016; 388: 2532-2561.

6 Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol [Epub ahead of print]. December 10 2018 Atv0000000000000073. http://www.ncbi.nlm.nih.gov/pubmed/?term=30580575.

7 Mitchell JD, Fergestrom N, Gage BF, et al. Impact of statins on cardiovascular outcomes following coronary artery calcium scoring. J Am Coll Cardiol. December 25 2018; 72: 3233–3242.

8 Cholesterol treatment trialists’ collaboration and others. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials. Lancet. February 2 2019; 393: 407-415.