Cholesterol-lowering medications are being prescribed to almost 30% of US adults aged 40 and over, most of these are statins drugs (1). The number increases with age, and approximately 48% of adults older than 75 are receiving such treatment.
It has been suggested that treating more older individuals with statins may prevent a substantial number of cardiovascular events, and that, if statins have no adverse effects on functional limitation or cognitive impairment, treating all elderly individuals will be cost-effective (2).
However, transforming public health targets into clinical practice is easier said than done because clinical medicine is an entirely different ball game, not least because of the human factor. For the clinician, explaining why a lifelong medication with potential side effects makes sense can be a difficult task. Furthermore, the situation gets more complicated if the treating physician realizes that many of those he or she manages to convince will not necessarily derive any benefit.
Three years ago the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines for cardiovascular risk assessment (3). Not unexpectedly, the debate on how to use statins in primary prevention took center stage.
Instead of using cholesterol levels to target treatment a new risk model was introduced, together with an online risk calculator (4). It was based on the assumption that a high level of evidence exists for the use of statin therapy in individuals with a ≥7.5% estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. The threshold to initiate statin therapy was later supported by risk-benefit and cost-effectiveness analyses (5).
In other words, to decide if a healthy individual should be treated with a statin drug, clinicians are offered an online calculator to assess risk. If the calculator shows that the risk of a cardiovascular event is higher than 7.5% for the next 10 years, statin treatment should be recommended.
The risk calculator itself is relatively user-friendly (6). The variables that have to be entered are race, gender, age, total cholesterol, HDL cholesterol, and systolic blood pressure. Furthermore, whether the individual has diabetes, treatment for hypertension or is a smoker has to be filled in as well. When all this is done, the calculator will report the 10-year ASCVD risk.
Should All Elderly People Be Treated?
What many of us found bizarre when testing the risk calculator was the strong influence of age. It turned out that all healthy individuals will automatically pass the 7.5% 10-year ASCVD risk threshold due to age alone, and thereby qualify for statin therapy, even if other risk factors are optimal. This will happen between age 63 and 71, depending on sex and ethnicity.
So, if we rely on the calculator, everybody will become eligible for statin treatment when they’ve reached a certain age, and everyone older than 70 will be on statins. Of course, this doesn’t make sense. Many elderly individuals will never experience a cardiovascular event. Why should they be given a drug to prevent something that will never happen?
Giving someone the benefit of the doubt can hardly be regarded as good clinical practice. Although statins are by many experts considered to be relatively harmless, adverse effects do occur. The elderly may be more vulnerable to adverse events due to the presence of other diseases and concomitant medication. Furthermore, one of the most feared side effects of statins, functional limitation and cognitive impairment, may easily go undetected among the elderly (7).
So although universal treatment of the elderly may be cost effective, from the patient’s and the clinician’s perspective, such an approach is misguided if not unethical.
How Can We Identify Those Who Benefit (The Biolmage Study)?
Because the use of the risk calculator will lead to unnecessary treatment of a vast number of individuals with statin drugs, the next question inevitably is how we can detect those who truly are at increased risk. By doing so, overtreatment is less likely to occur as treatment will be targeted at only those who are likely to benefit.
One way to do this is to use noninvasive imaging of the coronary or the carotid arteries to detect individuals with subclinical atherosclerosis. Thus, the decision to treat with statins could be guided by the absence (do not treat) or presence (treat) of subclinical atherosclerosis.This hypothesis was tested in the Biolmage Study and recently presented in a paper published in the Journal of the American College of Cardiology (8).
Biolmage was a prospective observational cohort of men 55-80 years of age and women 60 to 80 years old without ASCVD at baseline examination between January 2008 and June 2009. Imaging was performed in 5.805 participants to detect the presence or absence of subclinical atherosclerosis. The mean age of the population was 69 years, and 56% were women.
The purpose of the study was to evaluate a more personalized approach to primary prevention with statins by adding a simple disease guided reclassification step after formal ACC/AHA recommended risk assessment. All study participants underwent CT scanning to determine the coronary artery calcium score (CAC) and carotid ultrasound imaging to detect and quantify carotid plaque.
It turned out that the vast majority of these participants (86%) was eligible for statin therapy because of an estimated 10-year ASCVD risk above 7.5%. However, among those individuals, 28% had no coronary artery calcium, and 20% had no carotid plaque.
There was a strong correlation between subclinical atherosclerosis and clinical events. Event rates were low in participants without subclinical atherosclerosis, including those with diabetes.
According to the authors of the paper, those without subclinical atherosclerosis should be down-classified to non-statin eligible, despite high 10-year ASCVD. The number needed to screen (NNS) to find one person with a CAC of zero was 2.6 among those with a 10-year ASCVD of 7.5-15%.
However, subclinical atherosclerosis was also found in participants with 10-year ASCVD risk below 7.5%. These individuals should be upgraded to statin eligible because of the increased risk associated with subclinical atherosclerosis. The NNS to find one person with a CAC > 100 among participants with 10-year ASCVD risk of <5% and 5% to 7.5% was 10 and 5.3 respectively.
The Take Home Message
The recently published results from the Biolmage study may have several important implications for the practice of cardiovascular prevention.
The 2013 ACC/AHA guidelines support a universal treatment principle for the use of statins because everyone will qualify for treatment if they live long enough. Such an approach will likely lead to overtreatment and is unacceptable from the clinician’s standpoint as well as from the patient’s perspective.
The Biolmage data show that use of non-invasive imaging techniques to reveal the amount of coronary calcium or carotid plaque burden may be useful to reclassify patients as eligible or not eligible for statin treatment based on the presence or absence of subclinical atherosclerosis. In this elderly population assessing coronary artery calcium score (CAC) seemed to perform better than assessing carotid plaque burden.
Limiting primary prevention with statins to those with CAC above zero could spare 1 in 4 elderly from taking life-long medication that will benefit only a few.
The question about how to use statin drugs in primary prevention illustrates a huge gap between public health targets and clinical medicine. From the public health perspective, extending the use of statins, particularly among the elderly may seem an attractive target, not least because of the possible cost-effectiveness. However, due to the risk of side effects and the fact that many of those treated will not derive any benefit, the clinician should not prescribe statin therapy unless there is a high likelihood of benefit. The Biolmage data may have opened the door to new practical tools making it easier for physicians to advise their patients on this thorny issue.