As I said in my post last week, the now published ENHANCE study does not mean that Zetia is a bad drug, but that combining this drug with a statin (which is what Vytorin is) should not be used as first line therapy and adding to a statin when LDL goals are not met, may be beneficial.
Now, we have some evidence that this is in fact the case.
The SANDS study, reported in today's Journal of the American Medical Association shows that starting with a statin, and then adding Zetia improved atherosclerosis in diabetic patients treated to more aggressive LDL goals.
Bottom Line: If you have high cholesterol, your doctor says it needs to be lower, and diet and exercise won't get it down; first take a statin. If you can't take a statin or if a high dose statin can't get you to goal, then taking or adding Zetia is appropriate. If you get side effects with higher doses of statins, take the highest dose you can tolerate, then add Zetia if needed.
There is now really no good reason to ever start taking Vytorin. Though if you are on Vytorin, you should talk with your doctor before stopping.
For those who want more info:
The SANDS study looked at more aggressive goals for LDL (bad) cholesterol and blood pressure in patients with diabetes who are at very high risk for heart attacks and strokes. The took about 500 diabetic patients and half were treated to standard targets (LDL <100) and a systolic blood pressure (top number, SBP) of 130 mm Hg or lower. The other half was treated more aggressively to an LDL of 70 or lower and SBP of 115 mm Hg or lower. To look at progression of atherosclerosis (plaque build up), they measured by common carotid artery intimal medial thickness (IMT). The study showed that standard care group and progressive thickening of their arteries, but the aggressively treated group actually had regression or improvement. Unfortunately, there were no differences in deaths or heart attacks, but the rate of both were much lower than expected in the "normal" group, and it is possible that following these patients for a longer period of time will eventually show a difference.
The relation to Vytorin/Zetia is that in order to achive these more agressive blood pressure and cholesterol goals, more drugs were needed, including Zetia. More patients in the aggressive group got Zetia added to their statin medication, which was used first in both groups.
The ENHANCE trial also looked at the same outcome as SANDS, the CIMT.
In ENHANCE there was no improvement in CIMT when patients with very high cholesterol were given Zocor (simvistatin) 40mg or Zocor 40mg plus Zetia (Vytorin), even though Vytorin did lower the ldl more than the Zocor alone. This study got a lot of publicity for a number of reasons, but from a scientific standpoint it called into question the use of LDL as a target for cholesterol lowering. In addition to the multiple studies that show lowering LDL with a statin leads to fewer heart attacks and strokes, the SANDS study seems to confirm that LDL is indeed important, but in light of ENHANCE, how you get there is critical. You need to lower the LDL with a statin, but if you can not achieve LDL goals with a statin, you should add another medication like Zetia. The SANDS study is also important, because is suggests that patient with diabetes should be treated even more aggressively than current standards.
Zetia In, Vytorin Out.
Simvistatin, which is now generic, may be appropriate for many patients. However, it is not the most powerful statin. Newer drugs like Lipitor and Crestor are much more potent (and have CIMT, IVUS and other strong data to support preventing and even reversing atherosclerosis). At maximum dose, simvistatin 80mg can reduce LDL cholesterol by less than half, where as Lipitor and Crestor can achieve this at 20mg and 10mg respectively. Also, the higher the dose (regardless of potency) of a statin, the higher the chance of side effects. Thus, if you need your LDL reduced more than 40%, simvistatin is not likely going to be able to do this. In this situation, more potent statins such as Crestor and Lipitor should be used (as opposed to adding Zetia or starting with/switching to Vytorin which will decrease the LDL to goal, but may not lead to actual changes in the arteries). If a more potent statin can not achive LDL goals at a lower dose, a higher dose should be used. If this doesn't work (based at least on the diabetic patients in SANDS), then Zetia should be added since benefit was shown. Thus,
There is now really no good reason to ever start taking Vytorin.