By: Pallak Sharma, PharmD Candidate c/o 2022 and Rebecca Samuel, PharmD Candidate c/o 2022

             Statins, some of the most well-known cholesterol lowering medications, have been demonstrating increasing evidence of safety and benefits to the elderly patient population. ⁵ Statins are a class of medication that can help lower the level of low-density lipoprotein (LDL) cholesterol in the blood. LDL cholesterol is often referred to as “bad cholesterol”; and statins reduce the production of bad cholesterol inside the liver. High levels of LDL-C can be dangerous as it can contribute to the narrowing and hardening of the blood vessels (atherosclerosis), leading to cardiovascular disease. ⁵

Statins are currently indicated for patients with specific risk factors that predispose them to developing cardiovascular problems in the future. One of the main groups that are recommended for statin therapy includes people with a history of heart disease, stroke, or peripheral artery disease or risk factors that give them a 10 percent or greater chance of a heart attack within 10 years. That probability is calculated using the atherosclerotic cardiovascular disease (ASVCD) score which uses pooled cohort equations to estimate the 10-year primary risk of ASCVD among patients without pre-existing cardiovascular disease who are between 40 and 79 years of age. ⁴ Statin therapy is also indicated for people between the ages of 40 and 75 years old with diabetes. This patient population should be placed on moderate intensity statins and utilize risk estimates to consider high-intensity statins. Patients with diabetes and with multiple ASCVD risk factors should be considered for placement on high-intensity statins with the aim of lowering LDL-C levels by 50% or more. ¹ Another group of patients recommended for statin therapy includes individuals who are between the ages of 40 and 75 years of age with LDL-C ≥70 to <190 mg/dL and without diabetes. For this group of patients, the risk estimator should be used to decide which intensity of statin should be initiated. Those that fall under borderline risk (5%-<7.5%) should have a risk discussion with their provider and discuss moderate-intensity statins. Those with that fall under intermediate risk (≥7.5%-20%), should have a risk discussion on use of moderate-intensity statins and increase to high intensity if needed with the presence of increasing risk. Finally, those patients that fall under high risk (≥20%) should have a risk discussion to initiate high-intensity statin to reduce LDL-C by 50%. ¹ The last group of patients recommended for statin therapy includes people between the ages of 20 and 75 years old with an LDL-C level of 190 mg/dl or higher. This group should initiate a high-intensity statin without risk assessment. ¹

The cardiovascular protection that statins provide has led to its widespread use, especially in the elderly patient population. More than 60% of patients over 65 in the United States who have high cholesterol take a statin to prevent a heart attack or stroke. But in the case of many new drug trials, few subjects over the age of 75 are included. The early benefits and risks when statins were developed were not studied in the elderly population and were typically studied after the medication was on the market. However, the latest reports have been extremely reassuring.

A study was conducted where more than 120,000 French men and women between the ages of 75 and 79 were taking statins for up to four years. Within this select group, 10% of the subjects stopped taking the statin. Among this 10%, the risk of being admitted to the hospital for a cardiovascular event was approximately 25 to 30% greater than those who continued to take the statin. ³ Another study from Israel was published in the Journal of the American Geriatrics Society. This study involved nearly 20,000 patients over the age of 65 and these subjects were followed for 10 years. The chance of dying from any cause was 34% lower among the subjects that stayed on the statin therapy than those who failed to adhere to the statin therapy. The benefits were not reduced for those older than 75 for both men and women. ³ A study published in JAMA in 2020 by a team led by Dr. Ariela R.Orkaby of the VA Boston Healthcare System, involved United States Veterans with an average age of 81. There were 326,981 participants. This study showed the initiation of statin use was associated with 25% fewer deaths overall and 20% fewer cardiovascular deaths during a follow-up of approximately seven years. ³

These three studies do not provide the “gold-standard” of research. Typically, “gold- standard” means a randomized clinical trial was performed, whereas these three studies were conducted retrospectively. Two studies which have not been published yet, The Staree trial and the Preventable trial, both randomized controlled clinical trials, will study the topic of statin therapy to prevent cardiovascular events in the elderly while assessing cognitive function. ³ Although that data has not been collected yet, there are encouraging results from a report published in the Journal of the American College of Cardiology in 2019. This report stated there was no difference over a six-year period in the rate of decline in memory or cognitive status between those on statin therapy and those who have never taken the drugs. The report showed that those who started a statin during the study exhibited a blunted or slowed down rate of memory decline. ³

Apart from the benefit that statins provide on cholesterol, an observational study published in Nature by a Swedish team found that patients over the age of 65 who were taking statins experienced beneficial effects on reaction time and fluid intelligence.  There are also several reports that the lipophilic statins may have anticancer effects. A study of nearly 2,000 early-stage breast cancer survivors found a decreased five-year recurrence rate in women who started a statin within three years of the diagnosis. In a report presented by Dr. Kala Visvanathan of Johns Hopkins Medicine during a virtual meeting for the American Association for Cancer Research, a 40% reduction in deaths from ovarian cancer among more than 10,000 patients who were on statin therapy either before or after their diagnosis was observed. The population who benefited in this observational study was those who had the most common and aggressive form of ovarian cancer. Dr. Visvanathan attributes these findings to the fact that statins inhibit an enzyme in the chemical pathway of tumor growth and proliferation. There is hope to confirm these findings in a randomized clinical trial. ³

All of these studies not only show statin’s promise in the reduction of LDL-C, cardiovascular risk, and mortality but they also demonstrate some benefits beyond their FDA- approved indication. These results are great news for those already using these medications and should be reassuring for those over 65 thinking about starting statin therapy. Thankfully, statins have been around long enough for generics to become available and therefore they are more accessible to elderly patients. One of the best documented barriers to medication adherence is high out-of-pocket costs, even among individuals with prescription drug insurance. Numerous studies have found that increased drug copayments are associated with decreased use of prescription drugs, even for highly effective medications used to treat chronic conditions such as diabetes mellitus, hypertension, and hypercholesterolemia. ² The availability and affordability of these drugs as generics means its benefits can become widespread and easily implemented in cardiovascular care plans for the elderly if they were not included already.

References:

1. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;March 17:[Epub ahead of print].
2. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Medication adherence and use of generic drug therapies. Am J Manag Care. 2009;15(7):450-456.
3. Brody J. For Older People, Reassuring News in the Statin Debate. The New York Times. https://www.nytimes.com/2020/09/21/well/live/for-older-people-reassuring-news-in-the-statin- debate.html. Published 09/21/2020
4. Kane SP. ASCVD Risk Calculator: 10-Year Risk of First Cardiovascular Event Using Pooled Cohort Equations. ClinCalc: https://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx. Updated August 6, 2020. Accessed November 28, 2020.
5. Overview: Statins. NHS. https://www.nhs.uk/conditions/statins/. Published 11/19/2018.

Published by Rho Chi Post