CHICAGO – Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that – among other things – would identify whether they had a problem activating clopidogrel.
By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren’t aged 75 or older received the pricier, alternative agent prasugrel.
This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the annual scientific sessions of the American Heart Association.
The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.
Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics," Dr. Roden said in an interview.
"In the long perspective, every 50-year-old" is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but – stopping short of such global use right now – the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.
"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription," he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient’s record and finds the genotype information" to decide whether to flash a screen alert about the patient’s genotype and the implications.
The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs. Test results get posted into the record within a day of specimen collection.
So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money," said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.
Dr. Roden reported that he is or has been a consultant to Merck, Novartis, Sanofi-Aventis, Daiichi Sankyo, and Astellas and has received royalties from Clinical Data Inc.