At the American Heart Association meeting in Orlando, the results of the ARBITER 6-HALTS study were released. No Vytorin was used in the study, but I am sure that all the headlines will mention Vytorin.
The actual study published ahead of press online in the New England Journal of Medicine. Essentially, they enrolled over 200 patients from Walter Reed and Washington Adventist who had known heart disease or were at very high risk. These patients were already on a stable dose of a statin (40-50% on simvastatin – half of the Vytorin combination, and 40-50% on Lipitor) with an LDL cholesterol (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. 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.
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. Merck, 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.
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.
Matthew Mintz is an internal medicine physician and blogs at Dr. Mintz’ Blog.
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