Use of Statins in Management of Hypercholesterolemia

Erin D. Michos, MD, MHS, FACC, FASPC: Wow, we have a lot of work to do. Patients are not at their goal, and we’re underutilizing combination therapy. Some of this may be due to statin intolerance, perceived or real. Fortunately, we have newer agents for LDL [low-density lipoprotein] lowering. In our next segment, we’re going to dive deep into this; we’re going to talk about treatment options for hypercholesterolemia. But in this segment, Jorge, can we at least set the stage for why across all guidelines, statins are still first line, and why should we still try to prioritize statins when we can? What’s the evidence briefly behind statins?

Jorge Plutzky, MD: There’s incredible foundational evidence that statins are effective in reducing cardiovascular events. We’ve seen that progress from the very first trials of people with established cardiovascular disease, and LDLs that were elevated in 190 mg/dL range. Then we marched down from there to seeing people with less degrees of risk still have benefit from statin therapy. In those randomized placebo-controlled trials, they were very well-tolerated agents. That provides this basis between the efficacy of reducing events, and the safety and tolerability, and they have become our first go-to, and they’re now generic and readily available, and need to be utilized. One of the things we see is them not being utilized enough, in terms of titration at higher doses. This is often necessary because the biggest effect you get is with that first dose, and as you titrate up, you’re going to have lesser effects on LDL lowering with each titration. I believe most of us in preventive cardiology do that, we go on to higher doses. That evidence record is very strong, that lowering LDL with a statin will have benefits. Of course, there’s been a lot of thought about the other effects they may have, pleiotropic or otherwise. But we know that they work, and we know that they are generally well tolerated. So, it’s important to use them, even if we’re also thinking about how we move on to additional interventions.

Erin D. Michos, MD, MHS, FACC, FASPC: Pam, we all know that statins have this overwhelming evidence for benefit, and they are foundational therapy. But we heard also that patients are not achieving LDL goals in real-world practice. What is your approach when you have a patient on a statin who doesn’t appear to be achieving LDL goals? What are you thinking about? How do you address this in your clinical practice?

Pam Taub, MD, FACC, FASPC: You always want to uptitrate the statin to achieve your LDL goal, but statin intolerance is real. The studies estimate 5% to 30% of people have either partial or full statin intolerance. This concept of partial statin intolerance is new, but also very important. Some people can only tolerate a certain dose, and you just can’t titrate up any further or you induce adverse effects. So, we must recognize that there is statin intolerance. We cannot dismiss our patients when they tell us that they have adverse effects with a statin. The first thing I do is determine are there underlying metabolic derangements that I can correct that will help that patient not be intolerant to the statin? Some simple things to do are check thyroid levels, look at vitamin D levels, assess their alcohol intake, look at other drugs that could potentially increase the level of the statin. Those are some simple things. If you just look at that, there’s a significant number of patients you can get to tolerate a statin.

After you do that, if they still have adverse effects with the statin, you need to figure out what the maximum tolerated dose is. For most people, you can get on at least a low dose of a statin. There are some patients whose maximally tolerated statin dose is going to be 0, and this is where we have a lot of the nonstatin options. But ideally, we want to get patients on statins. Then there are all these nonstatin options we’re going to talk about that we can add. A lot of these nonstatin options, including the PCSK9 inhibitors and ezetimibe, have good cardiovascular outcome data.

Transcript edited for clarity