Bad Medicine: Supposed heart drug helper causes more heart attacks - http://www.usatoday.com/news/health/2007-06-17-heart-drug_N.htmIn December 2006, Pfizer, the world's largest drug company, put the kibosh on a 15,000 patient trial of a hopeful drug seen as the next blockbuster treatment for coronary artery disease.
A preliminary peek at the data by outside experts revealed that torceptrapib had a dark side. Reviewers found 60 percent more deaths had occurred among patients taking torceptrapib with Lipitor, a best-selling, cholesterol-lowering statin, than among those taking Lipitor alone.
The finding left the company no choice. It notified federal drug regulators, investors and the public and shelved the drug. (But what happened to the people who died during the drug study?)
Doctors are now trying to determine what made torceptrapib so deadly - and whether those risks extend to similar experimental drugs that raise high-density lipoprotein, or HDL, the so-called good cholesterol. The episode also leaves doctors groping for new drugs that, when paired with statins, can further reduce a patient's risk of heart attack and stroke.
How to exploit HDL and avoid its pitfalls are among the hottest questions in heart research: Studies show that people with lots of good cholesterol and low levels of bad cholesterol are less likely to have heart attacks and strokes. Steven Nissen of the Cleveland Clinic reported in 2003 that a super HDL, derived from human blood and dripped into arteries, actually reversed coronary artery disease within six weeks. Nissen likened the substance, Apo-A1 Milano, to Drano for arteries.
Pfizer hoped that torceptrapib in pill form, could achieve similar success. The firm was so confident that it staked $800 million on development.
But good cholesterol is more complicated than bad cholesterol. Reduce your blood levels of bad cholesterol, and you inevitably reduce your risk of heart disease. But good cholesterol comes in different forms. Some may be helpful; some not.
For instance, one of HDL's beneficial properties is to combat artery inflammation. Inflammation can worsen artery fat deposits and cause them to rupture, the deadly prelude to a heart attack. But some forms of HDL appear to worsen inflammation.
According to researchers, what makes torceptrapib's failure so frustrating is that the drug did everything its developers asked it to do:
- Raised the blood's supply of good cholesterol
- Reduced levels of bad cholesterol or low-density lipoproteins (LDL) that carry fats into arteries, where it can build up and block blood vessels.
But an early hint of trouble appeared in preliminary studies showing that torceptrapib can increase blood pressure. More bad news emerged in March showed that even though torceptrapib raises HDL, the resulting HDL lacks the muscle to scrub arteries.
What researchers are trying to figure out is whether torceptrapib is uniquely dangerous or poses risks that are common to all experimental drugs in this class. Doctors say torceptrapib's power to raise blood pressure may be a sign that the toxicity may be limited to the one drug. None of the other HDL boosters raise blood pressure.
