Pharmacy Times Interviewed Erin McConnell, PharmD, pharmacy quality program manager at the University of Pittsburgh Medical Center, discusses factors influencing cholesterol treatment management decisions and new treatments for high-risk patients.
Pharmacy Times: Statins, PSCK9 Inhibitors or newer agents like inclisiran?
McConnell: The cornerstone of treatment is a healthy lifestyle. This includes optimal body weight, smoking cessation, adequate exercise (usually around 150 minutes per week), and a diet low in saturated and trans-fatty acids and rich in dietary fiber, fruits, vegetables, and oily fish. If lifestyle changes alone are not sufficient or a combination with pharmacotherapy is recommended, we usually start with statins. These are the first-line drugs for this disease and should be considered in all patients unless there are contraindications or the patient has already tried multiple drugs and failed them due to ineffectiveness or unmitigable side effect problems. Statins lower LDL by 22% to 50%, depending on the drug and strength used. They also reduce both primary and secondary cardiovascular events and have the lowest cost.
And then from there we add alternative therapies, add therapies, offer alternative therapies. [which] It really depends on the patient’s clinical profile and situation. Then we look at drugs like inclisiran. [Leqvio; Novartis]is the next drug that can be added to statins and other lipid-lowering therapies. It will lower LDL by an additional 13% to 20%. Therefore, it is not very effective on its own and is usually used in addition. It has a low incidence of side effects and is now available as a generic drug, so it is fairly inexpensive. Therefore, if you need to lower your LDL even further, it is a good option.
Another option is PS inhibitors, which can be added to maximally tolerated statin therapy when further LDL lowering is required, lowering LDL by an additional 43-64%, or can be used alone when statin therapy is not appropriate or contraindicated. PCSK9s It is also an option for patients with familial disease, because these patients tend to have higher initial LDL levels and it can lower those levels to a greater extent than statins.
Recent data shows that these drugs are also effective in reducing major adverse cardiovascular events (MACE) and overall mortality in patients with CVD. There is some benefit beyond lowering LDL. And while the cost of these drugs has come down in recent years, their high cost tends to limit their use for some patients. You need to consider the risk-benefit profile for your patient and whether they can actually afford the drug.
Finally, there are several other types of drugs available: drugs such as inclisiran, an anti-ischemic small interfering ribonucleic acid agent, adenosine triphosphate citrate lyase inhibitors (ACLs), or bempedoic acid. [Nexletol; Esperion Therapeutics, Inc]; Angiopoietin-like protein 3 inhibitor Evanacumab [Evkeeza; Regeneron Pharmaceuticals, Inc]And finally, fibroids may also be an option for patients who need to further lower LDL or triglycerides in combination with a statin, or when statins are contraindicated or not tolerated compared with placebo.
The use of ACL inhibitors has been demonstrated to reduce the composite endpoint of cardiovascular death and nonfatal myocardial infarction. [MI] Reduced rates of stroke and other coronary revascularization procedures, fatal and non-fatal myocardial infarction and coronary revascularization procedures. And finally, FIB [fibrate] Patients with high triglycerides and low HDL levels may benefit from FIB rates, and there are studies showing that FIB rates can also reduce cardiovascular events. So, there are different options and different approaches that can be taken depending on the patient’s clinical profile.
Pharmacy TimesHow have recent updates to cholesterol management guidelines from the ACC and AHA impacted clinical practice?
McConnell: We still set targets for total cholesterol, LDL, and HDL, but as I mentioned, we try to look at the whole picture of the patient and what else is going on. The days of managing these high-risk patients solely with those targets are really over. Targets can and should be considered when selecting medications and when considering add-on or alternative therapies to statins. However, recent guidelines recommend adding a moderate or high-intensity statin drug to lifestyle therapy regardless of the patient’s current cholesterol levels. For example, high-intensity statin therapy should be initiated for patients of any age who have diabetes and also have ASCVD. Patients over 40 years of age with diabetes are at high risk of developing ASCVD, and moderate-intensity statin therapy can be used for patients under 75 years of age with ASCVD. Lower doses should be used if the patient has diabetes but does not currently have ASCVD based on the risk-benefit profile, if the patient is over 40 years of age and at low risk for cardiovascular disease due to diabetes, or if they have ASCVD and have a condition or drug interaction that may affect safety or are statin intolerant.
Options other than statins should also be considered, but some are not yet included in the guidelines because they are new to the market or did not have the same types of clinical outcomes as the older agents when the guidelines were last updated. Hence the emphasis on statins. I think we are seeing a gradual increase in adoption of these guidelines, which has been greatly facilitated by the incorporation of some quality measures in the National Quality Assessment Program. Pharmacists can play a role in educating both patients and providers about these updated recommendations for diabetes and CVD patients, the benefits of statin therapy in addition to LDL lowering, and how to continue statin therapy if certain side effects occur.
Pharmacy Times: What new or emerging therapies for cholesterol management are showing promise in clinical trials?
McConnell: Several chemical entities with new mechanisms of action are being investigated. Several of these agents have shown positive results in Phase 1 and Phase 2 trials and are currently in Phase 3 trials. I won’t go into too much detail on these agents because they are still a few years away from FDA approval, but I will say that they are also being studied for their ability to lower LDL more effectively without increasing side effects. They are also being studied to raise HDL for both primary and secondary prevention in a variety of conditions, including hypercholesterolemia and dyslipidemia, as mentioned earlier.
New indications for existing drugs are also being investigated. For example, inclisiran is effective in the treatment of homozygous familial hypercholesterolemia, coronary artery disease, primary hypercholesterolemia, mixed dyslipidemia, and in the prevention of cerebrovascular and cardiovascular events. And, oddly enough, resmetirom is [Rezdiffra; Madrigal Pharmaceuticals]is a drug recently approved by the FDA to treat the disease formerly known as NASH. [now known as non-alchoholic fatty liver disease]is being investigated for use in heterozygous common hypercholesterolemia, meaning it has a different mechanism of action than that drug.
