Despite science’s ability to develop sophisticated and targeted new drugs, predicting the effect of a drug in an individual is still maddeningly difficult. Not every drug works for everyone that takes it. Similarly, the very same drug can be well tolerated in some, but can cause intolerable side effects in others. So-called “targeted therapies” were supposed to improve our accuracy, by focusing on specific targets on cells. That’s been good – but not sufficient to make drug treatments more consistently effective. Pharmacogenomics is the relationship between your DNA and how your body responds to drugs: how they’re absorbed, how they work, and how they’re eliminated from the body. It has been heralded for some time as the white knight of drug therapy. The genome revolution was supposed to remove (or dramatically reduce) the uncertainty in medicine, telling us which drugs will work more effectively, and which we might want to avoid. And to some extent, the genome-based treatment era is already here. There are over 100 drugs approved by the Food and Drug Administration (FDA) now that include genomic information in their prescribing information. For a small number of drugs, genomic testing is warranted. Increasingly, genomic testing is more accessible, moving from the research bench directly into retail pharmacies for sale when you pick up your prescription. Given pharmacies have a less-than-stellar record of selling laboratory testing that isn’t validated or even useful, I was immediately skeptical when I saw a new story on pharmacy-based genomic testing. Titled “Your pharmacist’s secret weapon: How your DNA can help perfect your medication,” it appeared in last week’s Globe and Mail: (more…)
Posts Tagged warfarin
This will be a departure from my usual posts. Several announcements in the news and medical journals have caught my attention recently, and as I delved into the details, I thought I would share them with our SBM readers. Topics include AIDS cures, the continuing danger of polio, eating nuts for longevity, racial differences in vitamin D, and the use of pharmacogenetic testing to guide the dosage of anticoagulant drugs. They are all examples of science-based medicine in action.
Have patients been cured of AIDS?
I read that the HIV virus had returned in patients thought to have been cured by bone marrow transplants, and I mistakenly thought they were referring to the original claim of cure I had read about. Nope, that one still stands. (more…)
Critics of mainstream medicine often point to the dangers of drugs. I previously wrote about “Death by Medicine,” where I explained the fallacy of fixating on harmful effects of drugs without putting them into perspective with all the good drugs do. Yes, patients have died from severe allergic reactions to penicillin, but penicillin has also saved countless lives.
A recent article in The New England Journal of Medicine looks at emergency hospitalizations for adverse drug events in elderly Americans. It confirms that adverse reactions are a serious problem, but some of its findings are surprising.
On October 19, 2010, the FDA approved a long-awaited new drug, dabigatran, expected to replace warfarin (Coumadin) as a better way to prevent blood clots in susceptible patients. This provides an opportunity to re-visit several issues that we have addressed before, including Big Pharma tactics, drug approval by the FDA, deciding what is adequate evidence, applying science to clinical practice, and making individual health care decisions based on evidence that is sometimes incomplete.
Patients with atrial fibrillation, artificial heart valves, deep vein thrombosis, pulmonary embolism, antiphospholipid syndrome, and people undergoing certain types of surgery are at risk of blood clots, embolism, and stroke. They are currently being treated with rat poison. Warfarin (Coumadin) is an anticoagulant originally intended to kill rats. It inhibits the vitamin K dependent synthesis of several clotting factors. It saves human lives but is a mixed blessing. It takes several days to achieve therapeutic levels. Patients must be monitored with frequent blood tests to ensure that their prothrombin levels stay between an INR (international normalized ratio) of 2 and 3. When starting out, this means blood tests every couple of days. For some patients, dosage fluctuates and requires frequent adjustments; others can eventually drop down to a monthly blood test. Warfarin interacts with a long list of other drugs that raise or lower its blood levels. It interacts with many foods, and patients have to modify their diet. It can cause serious bleeding complications; while preventing thrombotic strokes it can cause hemorrhagic strokes. It is taken once daily. There is an antidote, vitamin K, that can reverse its effects promptly.
Warfarin is the 11th most prescribed drug in the US. Its benefits clearly outweigh its risks, but we wish the risks were fewer. We have yearned for a better option: something safer, something that would not require monitoring with blood tests, something that foods wouldn’t interfere with, something that would not interact with every other drug in the book. And now it seems we have it: a direct thrombin inhibitor called dabigatran.
Anticoagulation is advised for patients who have had a blood clot or who are at increased risk of blood clots because of atrial fibrillation, artificial heart valves, or other conditions. Over 30 million prescriptions are written every year in the US for the anticoagulant warfarin, best known under the brand name Coumadin. Originally developed as a rat poison, warfarin has proved very effective in preventing blood clots and saving lives; but too much anticoagulation leads to the opposite problem: bleeding. A high level of Coumadin might prevent a stroke from a blood clot only to cause a stroke from an intracranial bleed. The effect varies from person to person and from day to day depending on things like the amount of vitamin K in the diet and interactions with other medications. It requires careful monitoring with blood tests, and it is tricky because there is a delay between changing the dose and seeing the results.
In his book The Language of Life, Francis Collins predicts that Coumadin will be the first drug for which the so-called Dx-Rx paradigm — a genetic test (Dx) followed by a prescription (Rx) — will enter mainstream medical practice. FDA economists have estimated that by formally integrating genetic testing into routine warfarin therapy, the US alone would avoid 85,000 serious bleeding events and 17,000 strokes annually.
A recent news release from the American College of Cardiology described a paper at their annual meeting reporting a study of
896 people who, shortly after beginning warfarin therapy, gave a blood sample or cheek swab that was analyzed for expression of two genes — CYP2C9 and VKORC1 — that revealed sensitivity to warfarin. People with high sensitivity were put on a reduced dose of warfarin and had frequent blood tests. People with low sensitivity were given a higher dose of warfarin.
During the first six months that they took warfarin, those who underwent genetic testing were 31 percent less likely to be hospitalized for any reason and 29 percent less likely to be hospitalized for bleeding or thromboembolism than were a group that did not have genetic testing.
Epstein said that the cost of the genetic testing — $250 to $400 — would be justified by reduced hospitalization costs.
At this point, I don’t believe this study. I’ll explain why I’m skeptical. (more…)