Tailor statin therapy by carefully selecting patients based on their individual risk profiles, avoiding extreme views of universal use or complete avoidance.
Adopt a mindset where drugs are viewed as tools, aiming to have a broad range of therapeutic options and understanding the appropriate use and limitations of each.
Physicians should thoroughly educate themselves and their patients on the complexities of cholesterol and statin therapy to counter misinformation and ensure appropriate treatment decisions.
Utilize biomarkers and advanced risk assessment tools to precisely define an individual’s disease risk and effectively attack atherosclerosis by focusing on ApoB levels.
When selecting lipid-lowering drugs, prioritize those that enhance LDL receptor expression (e.g., statins, ezetimibe, PCSK9 inhibitors) as this mechanism has consistently shown to safely reduce clinical events.
Do not discontinue statins in high-risk patients, as these drugs are proven to save lives when directed at the right patients at the right times, despite common misconceptions.
Do not routinely monitor CK levels for statin toxicity; instead, rely on myopathic symptoms like aches or weakness to determine if a statin should be stopped, as minor CK elevations are not indicative of toxicity.
Do not routinely monitor liver function tests (aminases) to judge statin toxicity or liver issues caused by statins, as there is no established correlation in package inserts or guidelines.
Monitor serum desmosterol levels as a biomarker for brain cholesterol synthesis, especially in patients on statins, as statin use is the biggest reason for suppressed desmosterol synthesis.
If serum desmosterol levels fall below a certain threshold, consider adjusting statin therapy, as further statin use may not provide additional ApoB lowering benefit and could indicate excessive cholesterol synthesis inhibition.
Consider using a low-dose statin combined with ezetimibe to achieve similar ApoB reduction as high-dose statins, potentially with fewer side effects and less suppression of cholesterol synthesis in the brain.
If concerned about statins crossing the blood-brain barrier and potentially affecting the brain, choose hydrophilic statins like pravastatin, rosuvastatin, or pitavastatin, as they penetrate less easily than lipophilic ones.
When administering lipid-lowering therapy, measure phytosterols, stanols, and desmosterol to gain a comprehensive understanding of cholesterol absorption and synthesis pathways.
If phytosterols are considered injurious, ezetimibe is the only way to effectively prevent their absorption into the body.
Utilize ezetimibe as it is the most effective pharmacologic agent for increasing the excretion of cholesterol from the body via stool, thereby supporting reverse cholesterol transport.
Consider ezetimibe even for patients who are not hyperabsorbing cholesterol, as it can still provide additional ApoB-lowering and help keep phytosterols out of the body, mimicking a genetic model of longevity.
To identify optimal candidates for ezetimibe, assess phytosterols or other absorption proxies, as the drug specifically targets cholesterol absorption.
Consider fenofibrate for patients with elevated ApoB and elevated triglycerides, especially if statins or ezetimibe have not normalized these levels.
Consider fibrates for diabetic patients to potentially reduce microvascular complications such as retinopathy, amputations, peripheral neuropathy, and renal disease, based on secondary outcome data.
When using a fibrate in combination with a statin, choose fenofibrate over gemfibrozil to avoid drug interactions that can raise statin levels and increase the risk of myositis and rhabdomyolysis.
Monitor omega-3 levels in patients, as not everyone can convert EPA to DHA, and DHA is crucial for brain health and other functions, potentially requiring direct supplementation.
If the primary goal is additional ApoB lowering, consider prescribing high-dose EPA.
Advise patients to stop smoking and actively manage their blood pressure, as these are foundational interventions for preventing heart disease.
Do not be concerned that very low LDL cholesterol levels (e.g., 10-30 mg/dL) will impair hormone production or lead to other diseases, as genetic studies show no such deficiencies.
Be aware that cognitive impairment is listed as a potential side effect in the FDA package insert for all statins, indicating it can occur in some patients.
If a patient complains of cognitive impairment while on a statin, consider discontinuing the drug, as it is a potential cause and often the first explanation for such symptoms.
Continue to use statins as the backbone of antilipid therapy, but apply them thoughtfully and with individualized consideration for each patient’s unique profile and potential sensitivities.
Consider slowly migrating patients from Lipitor to Crestor, especially if they tolerate it well, as a preferred statin choice based on current practice trends.
Consider using pravastatin more frequently for patients who do not tolerate other statins or experience slight CK elevations, even without pain, due to its favorable profile.
Gain a deeper understanding of how laboratory tests are performed to better interpret results and identify potential blind spots in patient assessment, enhancing clinical acumen.
For highly statin-intolerant patients or those with specific conditions where statins have not shown benefit (e.g., aortic stenosis, chronic renal failure), consider alternative lipid-lowering therapies.
If concerned about statin side effects or over-suppression of cholesterol synthesis, consider reducing statin dose and adding ezetimibe or, if affordable and indicated, a PCSK9 inhibitor.
Be skeptical of claims extolling niacin’s efficacy for cardiovascular outcomes, as current evidence from well-designed trials has not consistently demonstrated positive results.
If considering niacin, be aware that clinical trials used massive pharmacological doses (e.g., 4 grams/day of immediate release), which are associated with significant side effects like flushing and pruritus.
Exercise caution with immediate-release niacin due to its high doses and common side effects, which make it largely intolerable for most people.
Understand that PCSK9 degrades LDL receptors, and inhibiting it (with PCSK9 inhibitors) improves LDL clearance, leading to lower LDL and reduced cardiovascular events, providing a strong rationale for its use.
Ideally, cholesterol synthesis inhibition should be targeted primarily to the liver, as it is the main tissue for upregulating LDL receptors and clearing LDL particles, minimizing inhibition in other tissues.