Some of you are wondering about my response to this news. First of all, you should know that I’m on Vytorin. My doctor had recommended a statin, along with omega-3 fatty acids for my increasing triglycerides and decreasing LDL (lethal) cholesterol. When my cholesterol particle counts (we don’t just follow my lipid profile) didn’t meet goal, my doctor added Zetia (using the statin and Zetia combination drug of Vytorin). Voilà, my particle counts are way normal.
Does this new information change my view about the reasonableness of adding either nyacin or Zetia to a statin as add-on drugs? Absolutely not. You can read my previous blogs on Zetia here:
In the meantime, for the many doctors who read this blog, I’ve solicited the opinion of a friend and internationally-recognized lipidologist, Tom Dayspring, MD. Here’s his response to the newest study data. It’s a long, and complex read, but well worth it for medical professionals:
By now you have likely heard something about the ARBITER-6 HALTS trial which was just presented at the AHA and published in the New England Journal of Medicine. Basically this is a trial designed to show what happens to carotid intima–media thickness (IMT) when either Zetia or Niaspan is added to a long term statin use.
For those who do not know, I am a consultant and National Speaker for both Abbott Labs and Merck (Schering Plough). I educate professionals all the time about aggressive use of lipid drugs to achieve goals.
I believe Niaspan, Zetia, fenofibrate, Trilipix, and Lovaza are grossly under prescribed. They are all potential “statin-helper” drugs.
Without outcome data (data on heart attacks, strokes, deaths), no one can ever state one combination is superior to another.
Readers of my newsletters know by now that statins have serious residual risk in all their trials and only get a minority of patients to apoB or LDL Particle Count (LDL-P) goal. Per all guidelines combination therapy is indicated to achieve goal.
There is zero Level One outcome data with any of the potentially available combination therapies that are out there right now.
So the only sane way to know what drugs to add to a statin is will the combo help me get to lipid goals (non-HDL-C) or lipoprotein goals like apoB or LDL-P and perhaps an emerging goal – HDL-P (not always the same thing as HDL-C)).
I happen to very much like both Niaspan and Zetia as wonderful statin-helping therapies.
I personally take 2000 mg of Niaspan as well as Zetia 10 mg every day (along with TriCor) along with once weekly statin (because of myalgia). And, I prescribe Zetia and Niaspan a lot in my practice to help achieve goal.
Based on multiple existing angiographic trials and now the ARBITER-6 HALTS trial it is my belief that if you have coronary heart disease (CHD), I want to know why Niaspan, unless it is not tolerated, is not part of your regimen to help achieve goal (except for unusual circumstances I never use niacin or Zetia monotherapy).
The ARBITER-6 HALTS trial was small, open-label (impossible to do a blinded trial with niacin) randomized trial enrolled CHD patients (with high or very high risk) who were on a statin for several years (mostly atorvastatin with some simvastatin) at or near LDL-C goal (all < 100 mg/dL).
They then received either Niaspan (extended release niacin) titrated to 2000 mg (a dose rarely used in the real world) or Zetia (ezetimibe) 10 mg daily. As expected there were more Niaspan dropouts due to drug side effects in the trial compared to Zetia.
The endpoint was change in carotid IMT over a year.
Unfortunately the trial was stopped prematurely, for no good reasons (both of the editorialists [see the editorials here and here] in the NEJM and the discussants at the AHA meeting agreed on that). Premature stoppage likely means whatever findings occurred are over-exaggerated.
Furthermore, the morons in the press are running around telling people they can take an over the counter vitamin for CHD. Niacin at 2000 mg or more mg per day is way beyond the vitamin dosage: it is a major pharmacological dose of a vitamin B3 and cannot be considered a vitamin at that dose and certainly has issues that must be followed.
Patients in the study had at goal or near goal LDL-C and borderline low HDL-C at the lower end of normal (remember baseline HDL-C was assayed while on a statin – not in a drug naive state).
Tragically the author did not see fit to measure the far more important parameters apoB or LDL-P or apoA-I or HDL-P. That is a mind boggling oversight in 2009 and it also makes it much more difficult to truly interpret what are the benefits of statin/Zetia (Vytorin) or statin/Niaspan (Simcor).
Most of these patients were on statins for over 5 years and thus their carotids have many years of statin therapy. Over the very short 14 month period of this trial the carotid IMT (CMIT) changes regressed on Niaspan/statin while statin/Zetia caused non-progression or miniscule regression (just like Crestor, a proven outcome therapy, did in METEOR).
Thus neither combination therapy failed, but Niaspan/statin induced what certainly seem to be more favorable changes than the statin/Zetia.
However there is no data that event reduction would be any different in patients with no progression versus regression. So until we have outcome trials, no one can conclude which combo therapy is in reality the best therapy.
Both editorialists and all discussants at AHA made that clear. However, let’s be also be very clear that based on CIMT changes statin/Niaspan was the winner.
However, because of the lack of data correlating therapy-produced, precise imaging changes to outcomes, there are no guidelines advising us to judge the efficacy of our drugs by performing repeat imaging procedures (including IMT).
Does everyone remember that estrogen, raloxifene, Fosamax and torcetrapib all have positive CIMT data and NONE have been shown to reduce cerebrovascular disease (CVD) events? Indeed both estrogen and torcetrapib also raise HDL-C.
Statin data on IMT changes are all over the map (positive and negative) yet all statins reduce outcomes. There does not seem to be much linkage. Pravachol reduces outcomes in its trials but was associated with plaque progression in an IVUS study (REVERSAL).
The lipids concentrations and presumably lipoprotein were beneficially altered with the addition of either Zetia or Niaspan. Zetia helped LDL-C more than niacin and niacin helped TG and HDL-C more than Zetia (no surprise there). Both drugs helped non-HDL-C.
My guess is the LDL-P (apoB) was fairly well controlled by the several years of statin use in this trial and both Zetia and Niacin further improved that crucial parameter (LDL-P or apoB). My guess is also that niacin improved apoA-I and total HDL-P and the Zetia did not. That would likely be a benefit in the Niaspan column.
Want to help lower apoB (LDL-P):
So, if I take a drug like Niaspan and can help a statin achieve better apoB levels and raise HDL-P levels, I think I have a great add on. Simcor would save be a copay, but Crestor/Niaspan would be the more potent therapy.
The ARBITER-6 HALTS trial certainly supports Niaspan/statin use. I prescribe Niaspan as they did in the study: get all patients to 2000 mg ASAP. I suggest you do the same. You cannot expect lower doses of Niaspan to achieve these results.
With proper advice, and perseverance Niaspan use is easier done than commonly believed. Abbott also offers a nice program to help patients properly take Niaspan. Talk to your reps.
This study does not change the fact that apoB (LDL-P) reduction is the primary goal, but it enforces the belief that raising HDL-P should be the secondary goal (by the way, fibrates raise HDL-P more so than niacin, yet fibrates, because of what they do to LDL size, do not raise HDL-C anywhere near what niacin does). This is one reason HDL-P is more informative than HDL-C.
If a patient on statin/Zetia is still not at LDL-P goals of therapy, Niaspan can help even if the HDL-C is not low. Also, if I have a patient on statin/Niaspan and LDL-P is not at goal I add Zetia. There is published data that statin/Zetia/Niaspan is a great lipid modulating triple therapy.
I want to conclude some of the what I consider outrageous statements made in the paper by the author.
In conclusions: FACTS:
Conclusion: Combination treatment with E/S plus N showed superior lipid-altering efficacy compared with N or E/S in type IIa or IIb hyperlipidemia patients and was generally well tolerated aside from N-associated flushing. This combination offers an effective, broad, lipid-altering therapy with improvements in lipid effects beyond LDL-C in these patients.
Tom Dayspring, MD