Congratulations to the two cardiologists who went public with crucial information rarely explained to the public. Their target: Heart drugs prescribed to healthy people who are expected take them every day for the rest of their lives. Guess what? These drugs can be great at improving your blood test results but not so great at helping you live longer or delaying the symptoms of heart disease. (And isn’t that the point, after all?) Billions of dollars were spent annually on drugs that, initially, showed promise that didn’t hold up with long-term scientific scrutiny. And too often, failure to prove any benefit does not dull the prescribing enthusiasm.
Vinay Prasad, MD, Northwestern University, Chicago, and Andrae Vandross, MD, Yale University, cite examples of widely prescribed drugs that were ultimately proven useless (Tricor), dangerous (extended-release niacin), or their advantage is uncertain (Zetia, Vytorin). In the current issue of Archives of Internal Medicine, the two cardiologists propose “setting the bar” higher for drugs prescribed to healthy people. This means clinical trials with a large number of healthy adults who are randomly assigned to take either the new drug or a placebo and are followed for many years. In other words, drug makers should prove their products can cut the rate of death, heart attack, stroke before the drugs are approved for healthy people.
As things stand now, drugs are usually approved after a few months of study on the basis of short-term results. For example, a drug must be better than a placebo at lowering cholesterol, or blood pressure, etc. It has long been assumed that this, in turn, will ultimately lower the rate of deaths from heart attack, stroke, etc. This assumption hasn’t always panned out. This was shown in 2006, when a much-anticipated drug called torcetrapib was in the process of getting FDA approval for its ability to greatly increase the so-called good cholesterol. But the clinical trial had to be stopped because the drug also increased the number of deaths and heart problems.
Occasionally, the large clinical trial proposed by the two cardiologists is, in fact, conducted—-but the results aren’t in for a decade or two after the drug was approved. Worse, prescriptions continue to rise for a drug found to be useless. One widely prescribed drug called fenofibrate (some brand names: Tricor, Lipofen, Antara) was approved by the FDA in 1993 for the treatment of very high triglycerides in the blood. Tricor became a blockbuster four years after a 2005 meta-analysis cast doubt on the benefits of all drugs in this class known as fibrates. There were no improvements in overall survival, and this was confirmed in a landmark clinical trial. “Although it was prescribed for more than a decade to further improve lipid profiles [standard test for fats in the blood] for patients already prescribed a statin, we now know the error of this practice.”
Cost is no small matter, as noted in this paper. “Annual spending on statins exceeded $19 million in 2005, ezetimibe (in the form of Vytorin and Zetia) costs over $5 billion in 2007, and fenofibrate costs passed $1 billion in 2009.”
Another improvement suggested by Drs. Prasad and Vandross: Drugs given to healthy people must be shown to lower the rate of deaths from all causes before they are approved. Too often a drug will lower the rate of heart-related deaths but not the total rate of deaths. If the drug succeeds with the former but not the latter, this raises the possibility that the drug itself is killing some people. The only way to rule this out is to demand that the clinical trials not only keep track of heart-related deaths but also total deaths.
If this sounds familiar, it is the same argument that has emerged over how to prove the lifesaving value of screening tests (also “prescribed” for healthy people). “While screening for breast, prostate, and colon cancer decreases cancer-specific death, none [emphasis added] have shown an overall mortality benefit in prospective trials,” wrote the two cardiologists. Screening can lead to potentially fatal, unnecessary, aggressive cancer treatments. click here for breast cancer screening, here for prostate cancer screening, and here for colorectal cancer.
Whether these excellent proposals ever see the light of day remains to be seen. After all, the current system of short-term pre-approval trials serves drug industry interests, and healthy people in early middle age are its favorite “market share.” (Unlike the sick and the elderly, healthy people have a longer lifespan ahead in which to take drugs.) It’s a good idea to think long and hard before accepting “preventive” drug therapy if you don’t have heart disease. Drs. Prasad and Vandross have given us the blueprint for the issues to be raised with the prescribing doctor.
Maryann Napoli, Center for Medical Consumers©