COMMENTARY

Vytorin/Zetia ACC Update (posted 4/3/2008) Nothing new presented, my position has not changed

Please see statement from the National Lipid Association regarding recent presentation of data originally discussed in January of this year.
NLA Statement on ENHANCE Study Findings: Premature Judgment Unwarranted
The limitations of the ENHANCE study, in terms of its design and the patients studied, are such that physicians should not alter their prescribing policies at this time. Current discussion regarding the ENHANCE Study is not based upon published work subject to peer review and thus cannot yet be evaluated by the medical community.
The ENHANCE trial was not powered to examine differences in clinical outcomes. The limitations in question include the patient population studied, which were patients who had familial hypercholesterolemia with an average baseline LDL-C of 319 mg/dL. The statin-ezetimibe combination reduced LDL-C more than did the statin alone. However, there were no statistically significant differences in the primary endpoint, which was carotid intimal-media thickness, as measured by ultrasound. The combination therapy (Vytorin) resulted in a greater reduction of LDL-C (17 percent) compared to simvastatin alone. Further, the therapy examined does not present safety concerns as there were no differences in adverse events between the two treatment groups.
Given that other studies are currently in progress to examine cardiovascular endpoints, generalization and extrapolation of ENHANCE results to different populations with regard to clinical outcomes is premature.
The National Cholesterol Education Program (NCEP) guidelines suggest patient goals but do not specify which drugs should be used to attain them. That matter is left to the judgment of the physician, whose primary objective is to help patients reach their treatment targets.
The NLA re-emphasizes the importance of following NCEP guidelines and ezetimibe and its combination form remain reasonable options that can be safely prescribed when appropriate. Until the ENHANCE Study is formally published and presented to the medical community, there is no basis on which physicians can make an informed decision and to do so now would be an unwarranted rush to judgment.

Zetia and Vytorin Update: NY Times Gets It Wrong

(Posted 1/16/08)

On January 14^th of this year the NY Times published and article in the business section reporting results of a clinical trial involving the drug ZETIA used in combination with the drug Simvastatin (previously know as ZOCOR). The study lasted two years and examined the role of high dose Simvastatin (80 mg) used alone versus in combination with Zetia (10 mg). The study was small (720 patients), and was done in a group of patients with a genetic disorder (familial hyperlipidemia) who had very high LDL cholesterol levels (bad cholesterol). The average LDL cholesterol for patients in this study was 320 mg/dl (normal being below 130). The patients were followed for two years and had ultrasounds of the carotid artery (major artery in the neck). The hypothesis being that the group taking Simvastatin and Zetia who lowered their LDL cholesterol on average to 133 mg/dl would have either less progression or more regression of atherosclerotic disease in the carotid arteries compared to the group taking Simvastatin alone (who lowered their cholesterol on average to only 187 mg /dl).

It is well know that to delay or actually regress atherosclerotic disease one must lower LDL cholesterol much lower than the levels achieved in this study , perhaps in the range of 70 mg/dl or even lower. Thus, it came as no surprise to myself or any other lipid specialist that the results of this study showed that there was no difference between the two groups, since neither group achieved very low cholesterol levels. This was because the levels were so high to start. The NY Times states that the group taking Zetia had “plaques that grew almost twice as fast s those taking Zocor alone” THIS IS FLAT OUT WRONG, AND INACCURATE. There was no statistical difference between the two groups. In an editorial released today the NY Times further compounds this misguided presentation by stating that since neither drug reduced plaque formation, “it seems clear that Zetia and Vytorin (Simvastatin + Zetia) should be used sparingly, in cases where all other drugs have failed”, again missing the point. The cholesterol levels in this study were so high to start that no current single available cholesterol agent currently on the market today would have reduced cholesterol levels enough to show beneficial changes in these patients. Does this mean that we should stop using all cholesterol drugs? Of course not.

My advice to patients taking Zetia or Vytorin is the following. DO NOT STOP YOUR MEDICATIONS. The reasons for taking Zetia remain the same. It should be used as add-on therapy to a Statin medication when the Statin alone does not lower cholesterol enough, or in patients who do not tolerate Statins in combination with other cholesterol lowering agents. Regarding side effects, the study under discussion showed that there was NO increased risk of side effects in the group that took Zetia, in fact there were fewer cases of muscle problems in the group that took the Zetia.

If you wish to discuss this further please call my office and set up an appointment.

Calcium Supplementation and Cardiovascular Risk (Posted 1/17/08)
Recently a group of medical researchers from New Zealand published the results of a clinical trial in the British Medical Journal that investigated the risk of heart disease in post-menopausal women who took calcium supplements. The basis for this investigation was that prior “observational studies” had suggested that there might be a cardiovascular protective effect for women who took calcium supplements. Earlier studies on the effects of calcium supplementation have shown that it both increases HDL (good) cholesterol and slightly decreases LDL (bad) cholesterol. The overall effect would be considered beneficial to preventing cardiovascular disease. Given the fact that many women, especially those who have progressed past menopause take calcium supplements to treat or prevent osteoporosis, it seemed reasonable to investigate this in further detail.

The study looked at a group of 1471 post-menopausal women who did NOT have osteoporosis, were NOT already taking calcium, and who had normal vitamin D levels. The average age of the women in this study was 74 . This study was what is called a “secondary endpoint study”, meaning that it was originally designed to look at something else (in this case hip fractures). For this reason secondary endpoint studies are often not set up to yield statistically significant results, i.e. there is a greater likelihood that the results may be due to chance. The patients were followed for a period of five years and the investigators looked at several different cardiovascular results. Half of the women took calcium citrate 1000 mg a day, the other half took placebo.

Many of the women in this study did not take their calcium regularly. In addition many of the events that happened were not documented, but merely reported by the patients; hence the accuracy may be questioned.

The final results showed a borderline significant increase in myocardial infarction (heart attacks) in the women who took calcium citrate, and a non-significant increase in stroke. The total number of women having events in both groups was small, and therefore these results must be interpreted very carefully. The study does not prove the calcium causes heart disease, but it does suggest that perhaps in older women who do NOT have osteoporosis or risk for osteoporosis, calcium supplementation should be reassessed. In younger perimenopausal, post menopausal or premenopausal women with or at risk for osteoporosis, calcium supplementation to prevent bone loss should be continued and may also have a cardioprotective effect.

My advice to patients is that if you are a women greater than 70 years old and do NOT have osteoporosis you may want to discuss discontinuing calcium supplementation. Younger women with osteoporosis or at risk should continue calcium supplementation.

If you wish to discuss this further please call the office to schedule an appointment