Melissa Walton-Shirley, MD; Roger S. Blumenthal, MD; Karol E. Watson, MD, PhD

Disclosures

May 02, 2014

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Statins: Discussion Before Prescription

Melissa Walton-Shirley, MD: Hi. I am Dr. Melissa Walton-Shirley, from theheart.org|Medscape Cardiology, and we are at the American College of Cardiology (ACC) 2014 Scientific Session. We are here to discuss lipid therapy. We have with us today Dr. Karol Watson from the University of California at Los Angeles (UCLA) and Dr. Roger Blumenthal from Johns Hopkins University. Thank you both very much for joining me.

We will get right into it. The current lipid treatment guidelines[1] include patients with any history of myocardial infarction, stroke, or established coronary disease; patients aged 40-75 years with a 7.5% higher risk for events in the next 10 years; those with diabetes aged 40-75 years; and patients older than 21 years with low-density lipoprotein cholesterol (LDL-C) levels higher than 190 mg/dL. Karol, have you heard anything at this meeting that influences your interpretation of those guidelines?

Karol E. Watson, MD, PhD: No. The guidelines are based on sound randomized, controlled clinical trial evidence, and nothing new has been presented that will influence how I'm going to treat patients.

I have heard some exciting things, however. The PCSK9 inhibitor trials[2,3,4,5,6] suggest that a newer agent could be available in the future, but we still have to see outcomes data on myocardial infarction, stroke, cardiovascular death, or any kind of clinical outcomes. We have seen robust LDL-C lowering with those agents.

Dr. Watson-Shirley: Indeed we have. We just need to match the dosage of statins to those used in trials. Roger, are the terms "low-, moderate-, or high-intensity statin therapy" obsolete now?

Roger S. Blumenthal, MD: From a primary prevention point of view, the moderate-intensity statins are probably what most clinicians think about starting, whether that is 10 mg or 20 mg of atorvastatin or 20 mg or 40 mg of simvastatin. For secondary prevention (the higher-risk individuals), we think about more high-intensity or high-potency statins -- eg, 40 mg or 80 mg of atorvastatin, or 20 mg or 40 mg of rosuvastatin.

I have one caveat. One of the nice things that came out of the meeting here is what Sanjay Kaul[7] talked about: the fact that just because a person is above that 7.5% risk threshold doesn't mean that it is mandated to begin statin therapy. Karol and her colleagues (on the guideline writing committee) talked about the need for a risk discussion. We know that older individuals may have a higher risk score, yet have very good lipid levels. Clinicians may decide to deal with the other risk factors in those individuals. It's not automatic that you have to prescribe a statin.

Dr. Watson: I agree. None of the recommendations are automatic. For every risk group, we recommend a patient/provider risk discussion to decide on the goals of therapy, whether we want to start a statin, and what the patient should be managed with.

Dr. Walton-Shirley: If we don't monitor levels, how do we determine compliance?

Dr. Watson: The guidelines do recommend that you monitor levels. We recommend that in the first 4-12 weeks, you get a lipid level, and then repeat this periodically to ensure adherence and to assess whether you have achieved the levels that you and the patient in conjunction have decided are optimal lipid levels.

Calcium Scoring: Who, When, and How Often?

Dr. Walton-Shirley: I want to ask you both about calcium scoring. I heard some very interesting data. They were retrospective trials, of course. Do you use calcium scoring in your practices?

Dr. Watson: In my practice -- and also in our clinical trial, which is the Multi-Ethnic Study of Atherosclerosis (MESA) trial -- we do a lot of calcium scoring.

Dr. Walton-Shirley: Let me give you a scenario. The patient is aged 65 years. Her mother had a heart attack at age 58, but oddly, the 65-year-old patient does not have calcium on her calcium score. Let's say she has a calcium score of zero, but her LDL-C is 180 mg/dL. Do you treat her or not?

Dr. Watson: I would do her risk assessment and estimate her 10-year risk. If her other risk factors are not elevated (her blood pressure is okay, no diabetes, and she doesn't smoke), she may not actually meet that risk threshold. So, I would not treat her, but I would continue to monitor and continue to enforce diet, exercise, and lifestyle.

Dr. Walton-Shirley: Roger, how would you approach the patient?

Dr. Blumenthal: I agree. Several articles from MESA have been published recently. One is by Seth Martin[8] showing that coronary calcium scoring clearly trumps the lipid abnormalities. Mike Silverman[9] showed also from MESA that calcium scoring is a much better predictor than the old Framingham risk score.

In that individual, I would do the same thing. I would try to work on lifestyle to bring down that LDL-C of 180 mg/dL.

Dr. Walton-Shirley: What if she says, when do I get my next calcium score? What would you recommend, just on the basis of your gestalt of the issue?

Dr. Blumenthal: In general, our data from MESA suggest about 7 years. If you truly have a zero calcium score and you don't smoke, you have an extremely low risk over the next 7.5 years. In the next 7.5 years, we might have some other therapies besides statins. I feel pretty comfortable that in that individual, over the next 5-7.5 years, we can just work on lifestyle. On the other hand, if that person has glucose intolerance or high blood pressure, then that may change the equation somewhat.

Dr. Walton-Shirley: Karol, do you agree?

Dr. Watson: I absolutely agree. We say once every 5 years if it's zero (a true zero) without high risk factors.

PCSK9 Inhibitors: Watch the LDL-C Plummet

Dr. Walton-Shirley: We heard about the PCSK9 inhibitors. They're all the rage and they should be, on the basis of the information that we have. In LAPLACE-2,[2,3,4] we added it to the statin and the LDL-C level plummeted. In GAUSS-2,[5,6] it was well tolerated in 300 statin-intolerant patients, with good LDL-C reduction. Do you think the fact that it's a subcutaneous injection will affect compliance? Will patients be more prone to take an injection every 2 weeks or monthly than to take a pill daily? How do you think that is going to play out?

Dr. Blumenthal: These will be individuals who can't get to a reasonable LDL-C level or people who are intolerant of statins. Because patients with diabetes routinely take injections, individuals who are truly high-risk will be compliant with once- or twice-a-month subcutaneous injections, assuming the outcome studies look good and that there are no off-target effects that would change the equation.

Dr. Walton-Shirley: Karol, it was at this presentation that I heard the rhetorical question of the century. What will we do with this medication if the US Food and Drug Administration (FDA) approves it without outcomes data? Do we really want to get on the same trajectory as ezetimibe and niacin with this medication?

Dr. Watson: My answer is, no we don't. I am hopeful that the FDA will not approve this medication for broad general use without outcomes data. If they do approve it, it may for the slim indication of patients with heterozygous or homozygous familial hypercholesterolemia, who are at such high risk that we are looking for whatever we can to help lower their massively elevated LDL-C levels. For a broad application, however, we really need outcomes trials, because we have been led astray by presumably very good lipid changes but not good outcomes.

Dr. Walton-Shirley: Should we be finished with surrogates for lipid therapy trials?

Dr. Blumenthal: Surrogates have been misleading at times. I agree with Karol that it will really be the outcome studies that will determine whether the guidelines will endorse other medicines on top of statin therapy for more routine use. In the back of clinicians' minds, they may very well have a secondary prevention patient, perhaps a post-bypass patient, in whom they are trying to do everything they can to minimize the recurrence of a cardiovascular event. Because there were somewhat favorable changes in dyslipidemic groups in ACCORD[10] and in AIM-HIGH,[11] some clinicians may selectively give fenofibrate or niacin on top of a high-potency statin, after a frank risk discussion that we clearly don't have definitive data. Some patients will want to do whatever they can to minimize an event. Other patients will prefer not to add that second medicine unless we have more compelling data.

Dr. Walton-Shirley: Karol, have you changed the way you prescribe ezetimibe? I don't prescribe it much.

Dr. Watson: On the basis of the clinical trial data, absolutely. We got lulled into thinking that lower LDL-C levels must translate into improved outcomes. Right now, statin therapy is so much more robust that if at all possible, I'm prescribing a statin. If patients are unable to tolerate a statin, then we can consider other options, but in general it's a statin-based world.

Dr. Walton-Shirley: Absolutely. Thank you both for joining us today on Medscape Cardiology and theheart.org for ACC 2014.

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