At the American Heart Association meeting in Orlando, FL they just released the results of the ARBITER 6 HALTS study. No Vytorin was used in the study, but I am sure that all the headlines will mention Vytorin... and for good reason.
Here is the actual study published ahead of press online in the New England Journal of Medicine. Essentially, the enrolled over 200 patients from Walter Reed and Washington Adventist (right in my home town!) who had known heart disease or were at very high risk. These patient were already on a stable dose of a statin (40-50% on simvastatin -half of the Vytorin combination, and 40-50% on Lipitor) with LDL cholesterols (bad cholesterol) under 100 and HDL (good cholesterol) under 50 for men/55 for women. These patients were randomized to receive either Zetia (the other half of Vytorin) or Niacin (though you can get this vitamin over the counter, patients received the extended release prescription version, whose maker is also the sponsor of the study). They were looking to see whether or not there would be difference in progression of atherosclerosis (clogging of the arteries) over 14 months as measured by carotid intima-medial thickness (CIMT), and ultrasound of the neck arteries which seems to be a good measure of plaque buildup in the coronary or heart arteries. News broke earlier this year that the study was stopped early because there was a clear winner, but we didn't know which drug won until now.
Patients who got the Niacin had their good cholesterol raised by close to 20%. bad cholesterol lowered by close to 10%. The Zetia group lowered bad cholesterol by close to 20% but also lowered the good cholesterol too. More importantly, those patients taking the Niacin had a reduction in the plaque buildup, whereas patients taking the Zetia had no change in plaque build up. Surprisingly, and inexplicably, the more Zetia lowered your cholesterol, the more plaque build up patients had. Finally, and most importantly, only 1% of patients in the Niacin group had major cardiovascular events, compared to 4% in the Zetia groups. This was statistically significant.
This trial has broader implications than just the Vytorin issue (which I will get to in a second). It suggests that patients at high risk for cardiovascular disease may have additional benefit beyond lowering their bad cholesterol. Though the addition of Niacin was proven to show benefit, it might be possible that other drugs which raise HDL such as fish oil and fenofibrate (Trilipix) might benefit at risk patients as well.
I have posted extensively on Vytorin in the past. Most of the controversy had to do with the ENHANCE trial which I discussed in my post Vytorin and Zetia: What to do now? Briefly, whereas multiple statin trials have shown that lowering LDL with a statin led to decreased heart attacks and stroke, Vytorin only had data showing it lowered the LDL. Merk, the makers of Zocor (simvastatin), Zetia, and Vytorin (Zocor + Zetia) funded a trial that, similar to the HALT study, looked at CIMT to measure plaque buildup. It compared simvastatin to the same dose of simvastatin plus Zetia, or Vytorin. Though Vytorin lowered cholesterol more that the simvastatin alone, there was no difference in plaque buildup. Defenders of Vytorin said that ENHANCE was not an outcome study (designed to study actual heart attacks and strokes) and that there were no differences in outcomes between the two groups. Though the HALT study was also not designed as an outcome study, findings were consistent AND there was a difference in heart attacks and strokes: about triple the number in the Vytorin group. My initial recommendation was that though Vytorin was really useless, if patients couldn't reach their goal with a potent statin or couldn't tolerate the statin, then using or adding Zetia was reasonable. This is probably still the case. However, in the HALT study differences were seen in HDL (went up for Niacin and down for Zetia), and this may account for some of the difference. For patients whose HDL was low, I will probably be a little more cautious of using or adding Zetia, which may make their HDL go down in addition to their LDL.
Bottom Line: There is no good use for Vytorin, and it may even cause harm, not because of safety, but because the LDL goals achieved with Vytorin may lead to fewer heart attacks that could be prevented with a more potent statin. If you are on Vytorin, ask you doctor about considering a switch.
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6 comments:
Thanks for discussion the negatives for the same...more awareness should be reached on this..
Wow - a lot to digest am glad you've so sucinctly put the issues together.
I'm a 55yo male & have a family history of heart disease in both father & older brother as well has blood cholesterol levels that are indicitative of the familial problems. I have been on many cholersterol drugs and most recently Vytorin (10/40) combined with OTC time release niacinamide. Having just completed a full cardio workup w/stress test & physical both MD's were extremely pleased with outcome & bloodwork.
4 days ago I suffered a TGA (Trans Global Amnesia) episode of approx 7 hours and still am not quite right with slight disorientation & disassociation. When researching amnesia and memory events I was shocked at the link to statins & stopped Vytorin immediately. Am thinking that a complicating factor was the addition of Vitamin D3 - 5000 IU daily to my meds following D3 testing as part of my routine physical. Given the family history I feel a need for the purported preventative benefits of statins but after a TGA episode and subsequent research, am scared to death to go back on them. Will have a contrast MRI the day after next to verify that nothing else is up but after reading about TGA's and statins I think the outcome is quite clear. Your thoughts?
TGA is pretty rare. Linkage to statins is weak, but have been reported as you mention. Not sure what statins you have tried, but one thought is that the lipophillic statins (Lipitor, Vytorin) are more likely to cross the blood brain barrier, and the hydrophillic statins (pravastatin and Crestor) are less likely to cross this barrier and get into the brain, so these might be theoretically safer and less likely to cause TGA. I am not aware of a report of Crestor and TGA. Given your strong family history, you have a few options.
1. Try Crestor.
2. Zetia-though ENHANCE and HALTS show no benefit of add on Zetia to statin, Zetia may have benefit in a high risk patient like yourself compared to placebo
3. Welchol-not as strong as lowering LDL cholesterol as a statin, but does lower it some. Should not cause TGA.
4. Welchol plus Zetia. Combination may give enough LDL reduction to come close to statin. Should not cause TGA.
Thanks for your very useful comments; will discuss the alternative of hydrophillic statins with my cardiologist & GP.
Based on the recent tests, my blood cholesterol is all within
the suggested limits - no extremes so I don't feel I'm overmedicated.
(How all of the reciptors work and the interactions are beyond my level of chemistry - but if I'm following, the Vytorin intended to block blood cholesertol, may be crossing the blood brain barrier thereby reducing the needed cholesterol used in brain function.)
The TGA episode occurred approx. 3 wks. after adding the Vit. D3 regimen. It is the only variable that has changed; have been on Vytorin and the other meds & supplements for over 2 years without side effects or issues.
A couple of questions:
1.) What effect if any, could the addition of D3 have had?
2.) Could addition of D3 either stimulating or interacting with a sector of the brain or somehow interacting or adding interference to what may already be going on with the Vytorin in the brain function?
3.) Any problems or potential implications of my cold turkey stopping of Vytorin?
not sure why D3 would cause this. Shouldn't be a problem with stopping Vytorin cold turkey
Have switched the Vytorin to Crestor, stayed on the Zetia and added Benicar. Results of the brain MRI and vascular study of the brain were negative, thankfully. Not sure if it was a TGA or TIA episode but hopefully the hydrophillic statin is a change in the right direction.
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