Using Niacin Plus Statins After AIM-HIGH
Using Niacin Plus Statins After AIM-HIGH
Hi. I'm Dr. Henry Black. I'm a Clinical Professor of Internal Medicine at the New York University School of Medicine and a member of the Center for the Prevention of Cardiovascular Disease.
There is a concern among preventive cardiologists that even though we have effective therapies, especially for lipids, and we can get low-density lipoprotein (LDL) down to below our targets, there still seem to be residual risks. I'm not sure if we can ever get the risk for cardiovascular events down to zero any more than we can get unemployment to zero.
The objective of the AIM-HIGH study that was recently published in the New England Journal of Medicine was to see if the addition of extended-release niacin to a full dose of a statin (and ezetimibe, if necessary) would reduce the risk for cardiovascular events. There was evidence from other studies that using niacin, usually in non-extended release, would reduce events. Surrogate studies have shown that a carotid intima-media thickness or atherosclerotic plaque could be reduced by niacin, but no events trials were done to show that the addition of those 2 agents [ie, a statin and ezetimibe] would really make a difference. That was the objective of the AIMHIGH study -- to see whether high-risk individuals who were mostly already on statins or ezetimibe and who had LDLs...in the low 70s would benefit from the addition of extended-release niacin to the current regime vs placebo. This was a placebo-controlled study that planned to show superiority, not inferiority [of the addition of 1500-2000 mg extended-release niacin] in a high-risk group of individuals who were already on statins. About 94% of patients in both groups were already on statins. The combined endpoint was cardiovascular events, deaths from cardiovascular events, myocardial infarction, stroke, and much of the usual issues.
The study cohort subjects...were very typical of what we see after cardiovascular events after percutaneous coronary intervention in high-risk individuals. The study was stopped about a year early for a couple of reasons. The major one was that it was clear that the hypothesis that the addition of niacin to simvastatin (usually at 40 mg plus ezetimibe, if needed) would reduce events was incorrect. The event rates in the niacin group and the placebo group were identical, about 16%, and although there was some benefit for other metabolic risk factors, there was no benefit in outcome.
Some of the lipid folks think that they didn't really study particle size, but they did study lipoprotein A, they did study high-density lipoprotein subfractions, and they were all pointing in the direction that niacin would help. However, the outcomes were identical. What do we make of this? Is it an issue of not having this modality to help us, or is it an issue about the fact that we can never get event rates as low as we think we would like to unless we begin to treat people much earlier and prevent the atherosclerotic damage that you see in coronary arteries and in other tissues?
It is interesting that there were more strokes in the niacin group, although not significantly, and that led to some concern because in observational studies and in smaller studies, the increased stroke risk was not there. What are we to make of that? From my perspective as a preventive cardiologist focusing more on blood pressure than on lipids, I would say that I don't have to add niacin. I don't think it's going to help. This was a somewhat selected group and they were already on statins, so maybe you're just not going to get much more benefit. The adverse events were a little greater in the group that got niacin, but the diabetes risk was very small, so I think our concerns about giving niacin to people with diabetes are probably not an issue. I think there are going to be some substudies and there are going to be some other issues when we begin to look at particle size more, but right now, there's no value in using extended-release niacin on top of statins.
Thank you very much.
Hi. I'm Dr. Henry Black. I'm a Clinical Professor of Internal Medicine at the New York University School of Medicine and a member of the Center for the Prevention of Cardiovascular Disease.
There is a concern among preventive cardiologists that even though we have effective therapies, especially for lipids, and we can get low-density lipoprotein (LDL) down to below our targets, there still seem to be residual risks. I'm not sure if we can ever get the risk for cardiovascular events down to zero any more than we can get unemployment to zero.
The objective of the AIM-HIGH study that was recently published in the New England Journal of Medicine was to see if the addition of extended-release niacin to a full dose of a statin (and ezetimibe, if necessary) would reduce the risk for cardiovascular events. There was evidence from other studies that using niacin, usually in non-extended release, would reduce events. Surrogate studies have shown that a carotid intima-media thickness or atherosclerotic plaque could be reduced by niacin, but no events trials were done to show that the addition of those 2 agents [ie, a statin and ezetimibe] would really make a difference. That was the objective of the AIMHIGH study -- to see whether high-risk individuals who were mostly already on statins or ezetimibe and who had LDLs...in the low 70s would benefit from the addition of extended-release niacin to the current regime vs placebo. This was a placebo-controlled study that planned to show superiority, not inferiority [of the addition of 1500-2000 mg extended-release niacin] in a high-risk group of individuals who were already on statins. About 94% of patients in both groups were already on statins. The combined endpoint was cardiovascular events, deaths from cardiovascular events, myocardial infarction, stroke, and much of the usual issues.
The study cohort subjects...were very typical of what we see after cardiovascular events after percutaneous coronary intervention in high-risk individuals. The study was stopped about a year early for a couple of reasons. The major one was that it was clear that the hypothesis that the addition of niacin to simvastatin (usually at 40 mg plus ezetimibe, if needed) would reduce events was incorrect. The event rates in the niacin group and the placebo group were identical, about 16%, and although there was some benefit for other metabolic risk factors, there was no benefit in outcome.
Some of the lipid folks think that they didn't really study particle size, but they did study lipoprotein A, they did study high-density lipoprotein subfractions, and they were all pointing in the direction that niacin would help. However, the outcomes were identical. What do we make of this? Is it an issue of not having this modality to help us, or is it an issue about the fact that we can never get event rates as low as we think we would like to unless we begin to treat people much earlier and prevent the atherosclerotic damage that you see in coronary arteries and in other tissues?
It is interesting that there were more strokes in the niacin group, although not significantly, and that led to some concern because in observational studies and in smaller studies, the increased stroke risk was not there. What are we to make of that? From my perspective as a preventive cardiologist focusing more on blood pressure than on lipids, I would say that I don't have to add niacin. I don't think it's going to help. This was a somewhat selected group and they were already on statins, so maybe you're just not going to get much more benefit. The adverse events were a little greater in the group that got niacin, but the diabetes risk was very small, so I think our concerns about giving niacin to people with diabetes are probably not an issue. I think there are going to be some substudies and there are going to be some other issues when we begin to look at particle size more, but right now, there's no value in using extended-release niacin on top of statins.
Thank you very much.
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