Friday, July 30, 2010

Preventing Heart Attacks: Is Crestor the answer?

In 2008, Dr. Paul Ridker, a physician-scientist from Harvard, published a study known as JUPITER, which found that Crestor (rosuvastatin) is beneficial in the primary prevention of cardiovascular disease, as it reduced the risk of MI, CVA and death.  

The trial studied males over 50 and women over 60 years of age. Both groups had LDL (bad) cholesterol <130, but they had to have one important risk factor: hs-CRP>2.  

Dr. Ridker believes that there is an important inflammatory component to coronary heart disease and pioneered the development of CRP, an inflammatory marker that is elevated in people at higher risk for cardiovascular disease. His theory was that this inflammation often precedes the hardening of the arteries, which is indirectly measured by cholesterol levels.  

The JUPITER trial was gutsy, because it was going to test whether or not this theory actually holds.  What if you took people with normal cholesterol levels, but elevated inflammatory markers (in the form of CRP) and treated them with a statin?  Would that reduce the development of cardiovascular disease? 

If so, it could be important proof that inflammation is a major driver of cardiovascular disease.  A corollary would be that waiting to treat until the cholesterol levels are high, might be waiting too long and that intervention should take place when the inflammatory process has begun.    

The results of the JUPITER trial seemed to come out strongly in favor of Dr. Ridker's theory.  Earlier this year, the FDA was also convinced and decided to grant permission for Crestor's use in primary prevention of cardiovascular disease. It suggested 3 criteria for use: 

  • Age (> 50 years in men; > 60 years in women), and
  • An elevated high-sensitivity C-reactive protein level (> 2 mg/L), and
  • Presence of at least one additional cardiovascular risk factor (e.g., high blood pressure, low HDL-C, smoking, or a family history of premature heart disease).
No other statin, such as Lipitor, has this permission.  Besides low-dose aspirin in men, no other drug is currently approved for primary prevention of cardiovascular disease.  

There have, however, been a lot of criticisms of the study.  Late in June, four papers came out in the Archives of Internal Medicine, all of which criticized the notion that statins are useful in primary prevention.  One of the studies, by Dr. de Lorgeril, targeted the JUPITER trial claiming it was flawed and that, "[t]he results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors."  

These papers have sparked a lot of controversy in the cardiovascular community, which is well summarized by this article on  What is interesting about the de Lorgeril paper is that it seems to personally attack Dr. Ridker and another physician, Dr. Rory Collins, which is unusual for someone to do in a scholarly paper. 

I do think these papers make an important point, which is that previous statin trials have not demonstrated benefit in primary prevention of cardiovascular disease.  Also, there was a slight increase in diabetes seen in patients on Crestor.  Lastly, the JUPITER trial was stopped after less than 2 years, so we don't have real long-term data on how these patients will do. It may be that the benefit from Crestor is short-term and not durable.  

It is also possible, however, that Crestor has unique properties that make it different from previous statins (it is far more potent than previous statins, for instance) and why it is able to show some benefit in this area.  In addition, it is important to remember that JUPITER did not take anyone with low cholesterol into the trial, only patients with low cholesterol and high CRP levels.  This kind of stratification hadn't really been done so explicitly in previous trials.  

At the end of the day, everyone agrees that diet, exercise and smoking cessation should be the initial interventions in people hoping to reduce cardiovascular risk.  Add in a baby aspirin if you are a high-risk male between 45 to 79 years old.  

As far as my own practice, I may consider Crestor for primary prevention in patients who meet the FDA prescribing guidelines (age, hs-CRP>2 and one other risk factor), but I may limit treatment to 2 years (as there is no data for treating patients longer).  In addition, I would counsel patients on the cost and side effect profile of Crestor and ensure they have already made therapeutic lifestyle changes.  

Of course, everyone is different and your decision should be made in consultation with a physician who knows your personal and family medical history.  

Wednesday, July 28, 2010

Pakistan's UN Ambassador speaks on US-Pakistani relations

An interesting interview of Abdullah Hussain Haroon, Pakistan's UN Ambassador, on The Brian Lehrer Show (click on the "Listen" link).  The interview came ahead of the 1st Annual New York Sufi Music Festival hosted by the Ambassador and the Pakistani Peace Builders Initiative.

Ambassador Haroon said some controversial things - like that Pakistan was a democracy before the United States because all Pakistani adults could vote in 1947 whereas blacks and women in America were not given true access to the ballot until the Civil Rights Act of 1964.

Whatever you think of Ambassador Haroon, he is quite confident of his opinions! He also made the case that Pakistan's sacrifice in fighting terrorism is not appreciated given the amount of Pakistani soldiers that have died helping US operations in Afghanistan.  But, overall, he was quite positive about Secretary of State Hillary Clinton and her approach to US-Pakistani relations.

Tuesday, July 27, 2010

The Cordoba House: A Community Center Maligned

A lot has been written about the Cordoba House, a plan to build a Muslim community center in Manhattan. Many excellent editorials have been written by open-minded Americans on why the House should be built and the importance of religious freedom in America (Washington Post, Sojourners, USA Today, Downtown ExpressJewish Daily Forward).

Another editorial worthy of attention, is the one written by NY Times editorialist Robert Wright, entitled, "A Mosque Maligned."  In his editorial, Wright actually shows how many of the attempts to malign Imam Feisul Abdul Rauf and his wife, Daisy Khan, actually have no connection to their own activities or viewpoints.

Imam Feisul subscribes to Sufism, a more spiritual approach to Islam.  You can see a talk he gave on how to live a spiritual life at beliefnet.  Both Imam Feisul and Daisy Khan have worked hard to show that terrorism has no place in Islam.  We should promote such efforts, both to defeat the evils of terrorist ideology and to honor the great American tradition of religious freedom.

You can keep up with media coverage of the Cordoba House via the newly launched Cordoba Initiative blog.

Monday, July 26, 2010

Enrollment in TIDE trial halted by FDA

The FDA has decided to halt further enrollment in the TIDE trial, a clinical trial sponsored by GlaxoSmithKline (GSK) to compare Avandia (rosiglitazone) to Actos (pioglitazone).  Avandia has come under a lot of fire recently, due to safety concerns, including increasing Congressional scrutiny.

The FDA released the following statement, which reads, in part:

The FDA has instructed GSK to update investigators, institutional review boards (IRBs) and ethics committees involved in the TIDE trial regarding new safety information presented at the joint FDA Advisory Committee meeting held on July 13 and 14, 2010, along with information regarding the deliberations and votes of that meeting.

The decision by the FDA is somewhat surprising given that the same FDA Advisory Committee meeting suggested keeping Avandia on the market, despite uncertainty over its safety profile.  

All in all, I think this is a smart, and surprisingly bold, move by the FDA. It is really advocating for patient safety, though a lot of this may be directly related to bi-partisan pressure from Congress and public perception that the FDA is too closely aligned with the pharmaceutical and medical device industries.  

Caffeine and Pregnancy

There is apparently a lot of debate in the ob/gyn community about how caffeine consumption affects pregnancy.  The American College of Obstetrics and Gynecology (ACOG) just released an opinion stating that <200mg (about one cup of coffee) per day does not increase the risk for miscarriage or preterm birth.  No conclusion could be made about the relationship between caffeine and intrauterine growth.

Dr. Barth, Chair of the Committee on Obstetric Practice, was quoted as saying, "Given the evidence, we should reassure our pregnant patients and let them know that it's OK to have a cup of coffee."

I'm not too surprised about ACOG's opinion, given the amount of tea South Asians drink, and I can't imagine all of our women giving up chai during pregnancy! Tea also has less caffeine content, about 100mg, than coffee, which may help. A reminder to pick your addictions wisely! :-)

Of course, one should always make any decisions regarding pregnancy and caffeine intake with one's physician, as every situation is different and depends on any underlying medical conditions.

Saturday, July 24, 2010

Friday, July 23, 2010

Money and Medicine: The Story of Avandia

Nice piece on the controversy surrounding Avandia, or rosiglitazone. I think it should be pulled from the market or that additional black box warnings accompany the medication.  Risk-benefit ratio just doesn't add up to me.

...of course, people should make their decisions in consultation with their physician, not my online musings...

This is a nice timeline of significant events with Avandia. Below is the video interview:

Watch the full episode. See more Need To Know.