Statin Initiation for Primary Prevention Among Statin Naïve Adults

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Vikas Sunder, MD:

Good morning, everyone. My name's Vic Sunder. I'm a cardiologist at the Cleveland Clinic who works in the section of Preventive Cardiology. Today we'll be talking about statin initiation for primary prevention among statin-naive adults and reasons for non-adherence.

Our latest guidelines for cholesterol management can be a bit overwhelming when you look at this algorithm of patients where we should consider statin therapy. We know that for patients between the ages of 40 and 75, an LDL cholesterol greater than 190 means that we should consider statin therapy for primary prevention. Similarly, for patients above the age of 40 with a history of type-2 diabetes, it's also class one recommendation to consider statin therapy for primary prevention. However, for patients where we calculate a ten-year risk in the intermediate or borderline range between five and 20%, we have to think a little bit more carefully and we have to consider the patient's entire clinical history and think about does this patient have ASCBD risk enhancers?

Now included in the guidelines are some sex-specific conditions such as preeclampsia and premature menopause, as well as a family history of premature atherosclerotic cardiovascular disease, south Asian ancestry, and autoimmune inflammatory disorders. We know now that atherosclerosis is a complex process. It's not just a lipid deposition disease, it also involves inflammation. Biomarkers are reasonable to check, including high-sensitivity CRP, apoB, as well as lipoprotein (a) levels. For these intermediate risk patients we can also consider doing coronary artery calcium scoring. If the calcium score is elevated, we can consider statin therapy as well for primary prevention. So here's an example of our ASCVD risk estimator through ACC, and there are web applications that can be used to calculate a ten-year risk profile. But the question becomes, what do we do about our patients younger than the age of 40, and when do we consider statin therapy for primary prevention in these patients specifically?

So for younger patients under the age of 40, we have to ask ourselves a couple of questions. Can this patient have familial hypercholesterolemia? Things that tip us off for this condition would be an LDL cholesterol greater than 190 or an LDL greater than 160 with a family history of premature atherosclerotic cardiovascular disease, and in patients who have this condition or have one of these factors, it may be reasonable to consider statin therapy for primary prevention. We know that familial hypercholesterolemia is highly underdiagnosed and the prevalence is about one in 250. And again, we want to look for certain lab values and features of the clinical history such as a family history of premature atherosclerotic cardiovascular disease as a starting point for diagnosing this condition.

In considering LDL lowering therapy, we know that having a high LDL at a young age confers a cumulative risk effect later in life. Even in those years between 18 and 30, this can be associated with a future cardiovascular event risk at a later age if you have a high LDL level. We also know that in younger patients under the age of 55, we see evidence of subclinical atherosclerosis. That's plaque not causing any significant issue, but evidence of plaque in these younger patients - iliofemoral plaque, carotid atherosclerosis, aortic atherosclerosis, and coronary calcifications. This process is starting in many of these younger patients even who have ten-year risk scores that are low by traditional risk equations, they do have some evidence of atherosclerosis.

When we look at statin utilization in the United States in adults between the ages of 40 and 75, even in the highest ASCVD risk category, greater than 20%, statin initiation for primary prevention lacks. Look at certain groups: African-American patients, 23%. Hispanic patients, 23%. So it lags behind in certain populations. And overall, when we look at the prevalence of statin use, less than 50% here is on our Y axis. Statin use for primary prevention in younger and older adults based on the PALM registry, this is about just over 60% or approximately 60%. But you look at the prescription of high-intensity statins for primary prevention, much lower, 10 to 12%. And interestingly, older adults were less likely to be prescribed high-intensity statins for secondary prevention. So the pooled cohort equations do perform well in populations that they were derived from.

The issue is there are certain populations that are excluded from this population, so we have to be considerate of that and think about the entire clinical history and do we have other tools now to estimate cardiovascular disease risk in patients under the age of 40 years? Understanding though that the pool cohort equations are still our guideline recommendation method for estimating risk. We now have the PREVENT equations, and this was available to us in November of 2023. This incorporates some more quantitative data such as the urine albumin-to-creatinine ratio, hemoglobin A1C, as well as a zip code that you can enter in for a patient. This estimates social deprivation index, which takes into account the location of the patient, their residence and factors related to employment, transportation, education, which we know plays an important role in cardiovascular disease prevention and risk estimation.

Using these quantitative parameters allows us to really stage in a bidirectional fashion. We know with cardiovascular kidney metabolic syndrome, you can move up a stage in severity but you can also move down. Seeing improvements in these quantitative parameters may allow us to reclassify risk of our patients. And here is just this data in tabular form that really shows the differences in these risk calculators. Now with the PREVENT calculator, you can get a 10 year risk and a 30 year risk. And this gives us a risk for ASCVD heart failure as well as a combined CVD or cardiovascular disease risk. And here are the differences in the derivation populations between the pooled cohort equations and PREVENT calculator.

Now we shift gears a little bit. So what are some reasons for statin non-adherence? We commonly in clinical practice hear about myalgias, concerns about side effects, forgetting to take the medication or patients thinking, hey, maybe there's a low benefit to taking this. So when we look at large cohort studies of more than 100,000 patients, although myalgias do represent about a quarter of the side effects experienced or the adverse events, overall it's again less than 5% based on this work done a number of years ago. So we hear about it a lot, but the overall incidence is relatively low. When we look at the PALM registry, again, about patients who are adults who are never on a statin but would be indicated for one, they can worry about side effects as a reason for not taking the medication or wanting to try diet and exercise.

When we think about adults previously on a statin who had stop the statin, most commonly we see that these adults experience some side effects. When we look at the drug approval studies, again, for different statins, overall muscle pain prevalence is relatively low as compared to placebo, particularly in our hydrophilic statins such as pravastatin. Interestingly, there was a clinical trial done a number of years ago that was a crossover study that randomized patients. This was a SAMSON trial to a placebo tablet, a statin tablet or no treatment. The findings were that there was no statistically significant difference in average symptom score. And again, these were all patients who had early discontinuation of statins. But when they were randomized placebo tablet versus statin tablet, [there was] no statistically significant difference in average symptom score. So what that alludes to is that this may be the nocebo effect. It might be tablet related side effects, not statin or pharmacologic related side effects.

So here's one algorithm proposed that I think is interesting for statin initiation. When patients have muscle-associated symptoms, if they're severe then we have to think about discontinuing the statin, checking a CK level to see if there's any evidence of myositis or rhabdomyolysis. Or if it's mild or moderate, addressing the nocebo effect. And then consider alternate dosing strategy such as using the statin a few times a week or every other day, or think about lowering the dose. And if the patient after trial of an alternate statin, change in dosing frequency or dosing strength is still having side effects then we have to think about our non-statin therapies, and we do have a number of those available these days.

What's interesting is, again, going back to the PALM registry, is when you look at patients, at least in this registry, for primary prevention that would qualify for statin therapy by our traditional guidelines, a number of them were never offered statin therapy. So 37% meeting ACC/AHA guidelines for primary prevention statin therapy not on a statin, of these patients 59% reporting never being offered a statin. Demographic correlates with the statin non-prescription were female sex, African-American or Hispanic ethnicity, lower rates of college education, or lower household incomes.

So statins are overall still underused in primary prevention, especially in certain underrepresented groups. The pooled cohort equations remain the ACC/AHA recommended standard approach to ASCVD risk estimation. The presence of high-risk features such as subclinical atherosclerosis or look for familial hypercholesterolemia, this should prompt consideration for early initiation of statin therapy. Statin side effects and intolerance should be adequately investigated first. We should consider challenging patients with dosing or agent modification, and non-statin therapies may be required in the setting of true intolerance to achieve adequate LDL lowering. Thank you all for your attention.

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