Alternate Mechanisms of Action for Cholesterol Management

Peter Salgo, MD: You did mention some other drugs. Zetia is one, and there are bile acid sequestrants. Where do you use these? Are they effective? Do they really work?

Howard Weintraub, MD: Sure. Ezetimibe blocks absorption of cholesterol in the small intestine. It is not extraordinarily effective in monotherapy. You get 14%, 13%, maybe 15% LDL reduction. It tends to work great with statins. I kind of refer to it as the Hamburger Helper for statins, because it does get a little, sort of a more robust, response with statins. But there are times in which people have been statin intolerant with 3 different drugs, and the letter comes back, “Has the patient been tried on Zetia?” This patient is 80 mg/dL away, they would require a 60% reduction, and they want to know if they have been on Zetia. And you write them a letter that says, “There is no force of man that could ever make this guy’s cholesterol come down.”

Peter Salgo, MD: I’m not talking about the letter to the insurance company. I’m talking about, does Zetia work?

Howard Weintraub, MD: Yes, it does. Zetia does work, in certain cases, where you’re not that far away from your goal. If you have someone with an LDL of 100 mg/dL, and you want them to be at 70 mg/dL, you can add Zetia.

Peter Salgo, MD: What about the side effect profile of all these drugs, the bile acids and the Zetia?

Howard Weintraub, MD: Zetia does have some first-pass effect in the liver. There have been liver function test abnormalities and myalgias, but not nearly as much as statins. The bile acid sequestrants are the earliest drugs that we had. Cholestyramine was the first; it’s largely constipating, binds to other drugs (and particularly the thyroid hormone), and if you give it to certain older patients, you get put on their very unfavored list because you’ve constipated them. There’s a newer version of it that’s a little less constipating, and it doesn’t bind to other medicines. But for that, too, we get a prior authorization (PA) request.

Seth J. Baum, MD: And it costs a fortune.

Howard Weintraub, MD: Yes.

Peter Salgo, MD: What I’m hearing is, yes, these are second-line drugs and they work with maximally tolerated doses of statins. And if you’re going to be a significant distance away from your goal, adding these drugs is probably not going to get you there.

Howard Weintraub, MD: Correct.

Seth J. Baum, MD: Right.

Peter Salgo, MD: Do you understand what they’re saying? If somebody asks, “Have you tried Zetia? Have you tried cholestyramine? It’s not going to work.” Why even bother?

Gary L. Johnson, MD, MBA: I totally agree.

Peter Salgo, MD: Do you agree, too?

Jennifer Strohecker, PharmD, BCPS: Yes, absolutely. As monotherapy, they’re not going to help a patient reach their goals.

Gary L. Johnson, MD, MBA: Or if you have a long way to goal, they’re not going to reach it.

Jennifer Strohecker, PharmD, BCPS: Yes, even as dual therapy.

Howard Weintraub, MD: I was talking more about add-ons.

Peter Salgo, MD: But even as add-ons, you’re saying if you are 30% away or 40% away, this isn’t going to get it done?

Jennifer Strohecker, PharmD, BCPS: Right.

Howard Weintraub, MD: Correct. And we’ve had letters insisting that we give them Zetia. We have to show 3 months of therapy and what numbers you get.

Jennifer Strohecker, PharmD, BCPS: Then you have to wonder who’s reviewing their PAs.

Howard Weintraub, MD: We have 1 person in the office, and just about all she does is the PAs, and she’s good.

Jennifer Strohecker, PharmD, BCPS: I’m saying within the health plan. Within the health plan, you have to wonder if the person who’s reviewing the PA is actually going through the mathematics of action.

Seth J. Baum, MD: But this problem is ubiquitous. And so, from a utilization management standpoint, there are problems in every insurance payer. And we just published an abstract at the American College of Cardiology meeting that looked at the IMS formulary, the IMS quintile database, and showed that regardless of statin dose—so high-intensity statin, use of ezetimibe, use of dual antiplatelet therapy (which is really tantamount to having vascular disease)—there is no difference between approved and denied in PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors across the board with either of them. So, something is radically wrong in terms of how people are reviewing the PAs.