Case-Based Evidence for Cardiovascular Risk Reduction - Episode 9
Deepak Bhatt, MD, MPH: Speaking of the next case, maybe we should move on to that. Jamie, that case is going to be one that you tee up for us. This was a woman in her early 60s with a history of hypertension, type 2 diabetes, and dyslipidemia. They often travel together, those risk factors. She is taking hydrochlorothiazide 12.5 mg every day, ramipril 10 mg a day, metoprolol 50 mg once a day, metformin 1 g bid [twice a day], and saxagliptin 5 mg a day. As it turns out, she didn't tolerate any statin regimen due to muscle complaints. Her total cholesterol is 230 mg/dL, the non-HDL [high-density lipoprotein] is 180 mg/dL, the triglycerides are 348 mg/dL. What are you going to do with her next?
James A. Underberg, MD: This is an interesting case, and I think this speaks to the art of medicine, that often we don't have evidence-based data to guide us. If we truly believe this woman is unable to take a statin, and as an expert in this area, I often see patients like this and ask them what does that mean? When you query people about their statement that they cannot take statins, it's often that they've tried 1 or 2 at very high doses, and they’ve decided they’re allergic to them or can’t take them.
I always want to make sure that we’ve tried every path toward some statin regimen, even if it's a longer acting statin such as rosuvastatin, once a week at a low dose. We try to get them on something. That's the first thing I would try to do with this woman. Because she is a high-risk diabetic patient, and when you look at someone her age, with hypertension, and lipid disorders, optimally, you'd want her to be on a moderate to high intensity statin. But unfortunately, we don't have a lot of evidence-based data for lipid lowering agents in the primary prevention space as monotherapy, other than statins. You could make the case to add ezetimibe. However, again, even though we have good data showing that ezetimibe, when added to a statin, seemed to have the best effect in the diabetic patients, it was on top of statin therapy.
You could make the same case for PCSK9 inhibitors, as another lipid lowering agent that at least in 1 of the 2 outcomes studies seemed to have a little better effect in diabetic patients, but always on top of statin therapy. In this case I think if you're going to use further lipid lowering therapy, you're doing it without a lot of good evidence-based outcome data to support that. Again, the idea of using 1 or the other as monotherapy or the 2 together is something that could be done, but you don't have a lot of data to support it. The question is whether this idea of statin intolerance poses a hurdle?
I think it is one that clearly is true. That's why I think trying multiple statins, as again, multiple different types of dosing regimens is reasonable. There was a great study in a journal called Cardiovascular Therapeutics, published several years ago. It was data from a lipid clinic in the United Kingdom. They looked at patients who were referred to them for muscle-related statin intolerance. Ultimately, they tried every statin available in the UK at the time. There were 6 different ones. They were able to get about 30% of those patients to be on a statin. We know, and again, from the PINNACLE data that somewhere between 29% and 37% of patients in high-risk cohorts don't get on statins or even non-statin therapies, so that's an issue.
But here is someone for whom we do have some evidence-based data when it comes to adding on icosapent ethyl, again on top of statin therapy, specifically in the primary prevention diabetic cohort, though, it's about as good as we're going to get. I do think that potentially ezetimibe and/or a PCSK9 inhibitor should be considered, but PCSK9 inhibitors are not approved for patients without heart disease or familial hypercholesterolemia. It's going to be very difficult to get her on that medication. I think ultimately this is a woman who may end up on ezetimibe as monotherapy and icosapent ethyl.
Deepak Bhatt, MD, MPH: Do you think that there is any particular value in pitavastatin in patients who are apparently intolerant to other statins?
James A. Underberg, MD: Well, I think there is value in another statin. Pitavastatin was the last statin available to us. Oftentimes when someone can take it and they do better, we have a moment of clarity and decide that it's better. It seems to probably have a better effect on dysglycemia and certainly the way it's metabolized gives you some reason to think that it might, in some patients, be better tolerated. I always try to use a different metabolic pathway than the one that's caused the problem. But ultimately, I think it's just because it's another statin that's available, it's always worth trying it if you can get a patient on it, and I'll try anything. So it’s a great thought.
Deepak Bhatt, MD, MPH: What do you think about the β-blocker here for presumably hypertension?
James A. Underberg, MD: If I were going to tweak her other medications, if we're starting to get outside of the lipid space now, I think there are 2 ideas. One, Bob spoke very eloquently about, some of the diabetes medicines of the newer classes, such as SGLT2 inhibitors and GLP-1 [glucagon-like peptide-1] agonists, especially in high-risk diabetic patients that I think might be more appropriate in a patient like this. Metoprolol is probably not the most lipid friendly agent that one could use for blood pressure control.
Even when you think about our newer blood pressure guidelines, it's lower down on the list now for management, so certainly that could have an impact on her triglycerides. We know that β-blockers can raise triglycerides, they can lower HDL cholesterol. She does have a rather significant dyslipidemia with a high non-HDL cholesterol. If you were going to use some of the newer formulas, like a Martin-Hopkins equation, to calculate her LDL [low-density lipoprotein], it would still be higher than it should be.
Ideally, she needs lipid lowering, but she really needs cardiovascular risk reduction more than anything.
Deepak Bhatt, MD, MPH: Right. The other thing that you alluded to, potentially her diabetic regimen could be tweaked. Saxagliptin is certainly a reasonable way to lower the glucose, but if she is just going to be on 1 other thing after metformin, I might have gone with an SGLT2 inhibitor or a GLP-1 agonist.
James A. Underberg, MD: We don't know her weight, but if she is obese or overweight that would be another reason that I would probably push in the direction of a GLP-1 agonist in that setting. She's already on metformin, and I'd leave her on that.
Deepak Bhatt, MD, MPH: Yes, I think I would do the same. Any other thoughts on her from the panel?
Robert Busch, MD: Deepak, if you added the SGLT2 inhibitor, you probably could get rid of the thiazide, and as you know, patients like getting rid of something when you add something, so the glucoretic effect of the SGLT2 might equal the diuretic effect of 12.5 mg of thiazide. There's where you negotiate, “I'll get rid of this, but I'm going to add this. This is a twofer that will lower your weight and your blood pressure.” And you can probably get rid of her saxagliptin then, if her A1C [glycated hemoglobin] was at goal. If not, I'd add it to that. This is because, as you said, saxagliptin has no cardiac benefit. It's safe but not beneficial.
Deepak Bhatt, MD, MPH: Yes, that's a great point. Not only could we add a number of medicines, as we said we would, but perhaps…
James A. Underberg, MD: Try pulling back.
Deepak Bhatt, MD, MPH: Yes, patients always like that. Any other thoughts on this case before we move on? All right, that was a good one there. We really completely redid her regimen.
Transcript Edited for Clarity