The Ins and Outs of Clinical Research Studies

The American Heart Association meeting took place in Orlando this year and provided additional insight into the treatment of heart disease. One study in particular was eagerly awaited. This was the Arbiter6-Halts study. Study results are embargoed before presentation or publication. What this means is that no results can be discussed or presented in any format until its release time. This is in spite of many people knowing the results. The only time this is not done is if something is of great importance to public health. Then it is rushed to print on line. The web has made this vastly easier but all the more difficult in that information often “escapes” early.

In Arbiter’s case, the study compared niacin — a drug that I have blogged about several times in the past.  It is a very useful drug but one that is very difficult to take secondary to side effects. As I have also blogged, we are presently involved in an early phase study working on a compound that acts like niacin without the side effects.

Niacin was being compared to Zetia, or as it is known generically, ezetimibe. I have not spoken much about this drug because of my own bias about it. It is, however, widely used and has undergone several evaluations; most have been negative as far as its use.

When this study was stopped early this past summer, Wall Street immediately began to dump the stock of the company that manufactures it. This was compounded by the chairman of the company having to have a conference call and providing negative earnings guidance for the company. This was all before the data was presented and individuals had an opportunity to review it. Just another example of how intertwined everything we do is.

Also involved in this issue is the difference between the old and new FDA approval process. In the past, as in Zetia’s case, drugs were approved because they lowered cholesterol. Now the drug must lower cholesterol and provide a clinical benefit. This is a high hurdle but a distinction that is critical. Why take a drug unless you get a benefit for it? When Zetia was approved it did not have outcome data. This is why these studies are so important.

Next…what is Zetia?

Tags: Arbiter6-Halts study, Ezetimibe, Niacin, Zetia
Posted in Cholesterol | 1 Comment »

Niacin: A beneficial drug

Recently we received a question on the blog regarding cholesterol treatment and the use of a test called Lp-PLA2. I thought I might dedicate a blog to the test and the rationale for it. I have discussed before the concept of evaluating your overall risk of cardiovascular disease by the use of the Framingham Risk Calculator as described in my blog from September 4, 2009 . If your risk is low, much of what we do to lower individual risks such as cholesterol or high blood pressure follows a more isolated approach. When the risk is high, a very aggressive approach needs to be taken to lower all the possible risk factors. Obviously, genetics at this time cannot be overcome.

Over time, many tests have come forward regarding cardiovascular risk. Almost all have some small value but none rise to the level of adding them to the risk calculator. Cholesterol has many components and we hold the most important to be LDL levels. If you can lower LDL levels primarily by statin drugs the known benefits are very impressive.

Recently, in the Journal of the American Medical Association (JAMA 2009; 302(4):412-423), a report on Emerging Risk Factors Collaboration was published. Researchers found, after reviewing the records of 126,634 patients, that Lp(a) was associated with risk, but that the effect was modest compared to LDL lowering. The only agent we have to lower the Lp(a) levels is niacin, which also lowers LDL and raises HDL; so it is not specific.

In the example provided in the comment, the substitution of a more potent statin to drive the LDL below 100 would be useful. Lovaza in doses of greater than 1 gram a day may actually raise LDL levels. Niacin in any dose would be the most beneficial drug because it will lower LDL, triglycerides and raise HDL. As you can see, it will also lower Lp(a). Talk to your doctor about taking niacin. In general, we recommend: starting with 500mg a night and increasing the dose to 2000mg if possible very slowly; and taking only slow released compounds after taking an aspirin and before going to bed.

Tags: Framingham Risk Calculator, HDL, JAMA, LDL levels, Lovaza, Lp(a), Lp-PLA2, Niacin, triglycerides
Posted in Cholesterol | No Comments »

Study to Lower Cholesterol Now Enrolling

I have been involved with the study of compounds regulating cholesterol synthesis in many different forms, and have been principal investigator of many clinical trials studying this topic. Our newest study here at the JMHVRI will be headed by Dr. Molly Zachariah. This study sponsored by Schering-Plough is to test the safety of SCH 900271 in patients with high cholesterol for a period of 8 weeks. The entire study can last for up to 22 weeks.The compound being tested is a nicotinic acid (nothing to do with nicotine from cigarettes) receptor agonist. This drug is to mimic the use of niacin, which is useful in raising HDL, but is very difficult to take because of side effects, primarily itching and flushing. Raising HDL 1% lowers cardiovascular mortality by up to 3%.

Niacin was first identified in 1873 by Hugo Weidel and is the vitamin which prevents the disease pellagra, one of the five diseases caused by vitamin deficiency. The name comes from the contraction NIcotinic ACid + vitamIN. It is Vitamin B3. In cardiology it is used to reduce total cholesterol, triglycerides, very-low-density lipoprotein, LDL and increase HDL. Niacin blocks the breakdown of fats to VLDL. Doses used are generally 1000-2000mg. two to three times a day.

Even when given in special preparations the agent causes troubling itching and flushing. Although harmless, the reactions are difficult to tolerate even in highly committed patients. This study will evaluate the compound for safety and effects on patients with documented levels of cholesterol. If successful, the compound will then go on to the next stage of study for efficacy.

To be considered for this study, patients may not take lipid lowering agents, such as Lipitor or other common drugs. These individuals are excluded from participation in the study. The individuals we are most interested in are those whose cholesterol problems are being treated by diet modification.

If you are interested please call the JMHVRI at 954-229-8400.

Tags: cholesterol synthesis, Niacin
Posted in Cholesterol | 3 Comments »