The most over prescribed medication: Statins
Statins, often hailed as miraculous, are among the most widely used medications globally, second only to aspirin. While aspirin doesn't require a prescription, statins, for now, remain a prescribed medication. The debate over whether statins should be available over-the-counter (OTC) has sparked controversy, similar to what happened in England. Interestingly, other potent drugs like proton pump inhibitors (PPIs) such as Nexium or Prilosec have risen to OTC status in the United States, prompting curiosity about the future of statins in the OTC market.
If you don’t know what statins are, you probably never watched the evening news where the drugs have been widely advertised since the beginning of direct to consumer (DTC) advertising on TV. And no surprise, DTC ads for statins boost sales. Everyone knows someone on a statin. I think the selling of statins and drugs for male ED (erectile dysfunction) have made consumer ads so successful today. Since most statins are now generic, most of the consumer advertising in the evening news is about newer costly biological and other specialty drugs for conditions such as rheumatoid arthritis (RA) and cancer.
I remember when the first-ever statin became available from Merck in 1987 under the trade name Mevacor (lovastatin). I was early in my internal medicine practice career. I was always hesitant to be the first to prescribe something new. I recall the original recommendations suggested checking routine liver function tests and there was some concern about cataracts. Yet lowering cholesterol seemed like a pretty important deal. The widely publicized Framingham study study in 1970 taught us that cholesterol, smoking and high blood pressure were all intimately related to heart disease.
Many Americans had high cholesterol levels, even by the much less rigorous criteria proposed back then. But the original cholesterol-lowering medications worked poorly and had terrible side effects. I remember vividly the flushing patients experienced with nicotinic acid and the constipation and dietary warnings with cholestyramine. So when Mevacor came along, people with high cholesterol were happy to have this new alternative.
Implementing dietary changes to manage cholesterol levels can be challenging, particularly in societies with a predominant focus on meat and dairy consumption. In the past, there was a misconception that statins could replace the need for dietary adjustments, leading some to believe they could indulge freely in meat and dairy. While this mindset persists in some individuals, there is a positive shift towards the popularity of vegan and non-animal product diets, accompanied by a broader adoption of healthier lifestyles.
These dietary changes have proven to significantly impact cholesterol levels and address underlying heart disease. Dean Ornish, MD, is most famous for promoting a healthy lifestyle, and he has the evidence to prove it. His latest book is a great and inspirational summary of his findings. I met him and heard his inspirational message years ago and have not forgotten.
In our bodies, cholesterol production is predominantly carried out by the liver, accounting for about 75% of the cholesterol in our blood, while dietary sources contribute to approximately 25%. Statins effectively target and block the liver's cholesterol production, THEY DO NOT block cholesterol absorption from the foods you eat. So if you take a statin along with a fatty high cholesterol meal, you are somewhat defeating the purpose of a statin. Your fatty meal will still be absorbed through your gut and could have a bad impact on your arteries even if you take a statin. Timing of statin administration can also play a role in their efficacy.
Longer-acting statins like atorvastatin and rosuvastatin exhibit optimal results when taken in the evening during a fasting state. However, it's crucial to be cautious with certain interactions, such as consuming grapefruit juice along with statins. Research indicates that grapefruit juice can amplify the effects of statins, with a single glass potentially equaling three times the statin dose, leading to potential adverse effects.
In 1997, just ten years after the first statin was approved, the famous 4S trial was published with great fanfare. This influential study showcased the undeniable reduction in mortality among individuals with known heart disease who received simvastatin (Zocor), encompassing both men and women aged 35 to 70 years. The benefits were seen as early as one month of starting the drug in these high-risk patients.
Since 1997 there have been many studies worldwide demonstrating the benefit of treating patients with heart disease or stroke. There is no doubt that statins save lives and reduce heart attacks and stroke in patients who have cardiovascular disease and diabetes. By significantly lowering cholesterol levels, statins reduce heart attack and stroke risk by up to 30%, a result also attainable through adherence to strict vegan diets and embracing a healthy lifestyle.
When it comes to the use of statins in older adults, particularly those aged 75 and older, there is a surprising scarcity of evidence supporting their effectiveness for primary prevention. There have been no comprehensive, large-scale clinical trials dedicated to studying the typical older patient, who often faces an elevated risk of heart disease and is simultaneously managing multiple medical conditions and medications.. The United States Preventive Services Task Force (USPSTF), known for it’s conservative and evidence based approach concluded that the “current evidence is insufficient to assess the balance of benefits and harms of initiating statin use for the primary prevention of cardiovascular disease (CVD) events and mortality in adults 76 years and older without a history of heart attack or stroke.” Unlike younger adults, older adults, particularly women, are more susceptible to experiencing serious side effects associated with statin use. Although muscle symptoms may be reversible upon discontinuing the drug or transitioning to another type, dismissing or overlooking these symptoms can lead to increased weakness, falls, and loss of function.
The main goal of primary prevention with statins is to achieve a net benefit more than risk from treatment. We must carefully weigh the potential benefits against the risks before commencing any drug regimen. Notably, not all individuals undergoing primary prevention treatment, such as statin therapy, will necessarily develop heart disease, and thus, they may not reap its benefits. Yet they are subject to the same risks of the drug. Additionally, as individuals age and contend with increased frailty, multiple medical conditions, and a complex array of medications (polypharmacy), the likelihood of experiencing adverse statin-related symptoms dramatically increases. The “risk-benefit” balance for many elderly could tip in favor of avoiding statin therapy.
A good friend had a small dinner party not too long ago. When a guest heard what I was blogging about, she lit up and told me her concerns about her 92-year-old father. Her father was in excellent health, had no previous heart disease, and yet he was taking a list of medications, including a statin. She was worried as she heard about possible cognitive decline and didn’t want to risk that for her dad, who was becoming a bit more confused.
She asked me what she should have her dad do. Although I couldn’t give her specific medical advice, I did suggest that bringing up her concerns about her father with her father or his physician may help. A trial of stopping it may help her father decide how he feels off the medication. I reminded her that we just don’t know how best to treat someone her father’s age who has been taking statins for a long time. Following the adage “less is more” is a good plan, especially as seniors age and take more and more medication.
Another helpful reference for those healthy adults over 75 considering whether to take statins is The Choosing Wisely campaign of the American Board of Internal Medicine. They ask the question of older adults, “Are you more concerned about preventing a heart attack that might never happen? Or do you want to avoid side effects that can lead to frailty, injury, and memory problems?”
For those who remain uncertain about statin use and my friend's father, it is crucial to acknowledge that the risks and benefits of statins in older adults have never undergone a comprehensive evaluation through a large, scientifically rigorous trial. In 2017, the National Institute on Aging and the National Heart, Lung, and Blood Institute assembled an expert panel tasked with examining the existing evidence.
Their focus was to determine if the research on statin safety and effectiveness in individuals aged 75 and above without ASCVD (atherosclerotic cardiovascular disease) was sufficient. More than 40% of adults aged 75 and older without heart disease continue taking statins for primary prevention, despite the absence of evidence supporting their benefit in this context.
In 2015, there was the launch of the first primary prevention study of statins in those aged over 70 in Australia – the STAREE trial. STAREE is a double-blind, randomized, placebo-controlled primary prevention trial (the gold standard of clinical studies) designed to assess whether daily treatment of 40 mg atorvastatin (Lipitor) will enhance disability-free survival (death, dementia, and disability) and prevent major cardiovascular outcomes (heart attack, stroke) in healthy participants aged 70 years and over. The STAREE study results will hopefully provide substantial evidence about the use of statins in the elderly. The earliest results were expected in 2019, although the study will not conclude until 2023. In the meantime, stay tuned. PS: COVID-19 delayed recruitment of patients so the study has been extended another 18 months.
As always, I welcome your questions and comments. My warmest regards, Dr. Marie, Marie Savard, MD