Psaty and colleagues specialize in long-term studies of heart disease drugs

Dr. Bruce M. Psaty and his colleagues are a highly trained surveillance team. They analyze data from a drug epidemic in the United States for results that may save lives. What is different about this war on drugs, however, is that the drugs involved are legal.

Bruce Psaty

Approximately 70 percent of people over the age of 65 take an average of 2.8 different drugs per day for a myriad of conditions, said Psaty, a professor of medicine in the School of Medicine and epidemiology in the School of Public Health and Community Medicine. He is co-director of the UW Cardiovascular Health Research Unit (CHRU). The pharmaceutical companies that supply these drugs are a $100 billion-per-year industry, he added.

“This is an epidemic of drug use,” Psaty said.

Psaty and colleagues, notably Dr. David Siscovick, professor of medicine and epidemiology and co-director of the CHRU, and Drs. Susan Heckbert and Stephen M. Schwartz, professors of epidemiology, cite instances of the U.S. Food and Drug Administration pulling drugs from the market after the adverse effects of the drug are found to be greater than estimated in experimental clinical trials. The problem, they say, is that preapproval trials are often not large enough and not long enough.

“If a person is going to take a medication for many years, trials of a few months duration are probably not adequate to assess the long-term safety,” Psaty said.

The FDA uses evidence from randomized clinical trials to determine whether an experimental drug is effective. In these trials, researchers compare the experimental use of a drug in one group of patients with standard therapy or no treatment in other groups. These trials are usually small and measure efficacy based on differences in endpoints such as blood pressure or cholesterol levels. Psaty’s studies, on the other hand, focus on major disease endpoints, such as heart attacks or strokes. In what can be described as “observational studies,” he and his colleagues analyze years of data to determine outcomes in patients who have received various approved therapies.

“These large, long-term trials are often not done,” Psaty said. “Pharmaceutical companies have been unwilling to conduct these trials to evaluate more fully the safety and efficacy of commonly used and sometimes expensive medications.”

In a study published in the Journal of the American Medical Association in 1995, Psaty and his colleagues compared the association between heart attacks and the use of various hypertensive agents.

The patients were enrollees of Group Health Cooperative of Puget Sound who had been diagnosed with hypertension and were receiving at least one medication to treat high blood pressure. Psaty found that the incidence of first heart attacks was significantly higher in patients who received short-acting calcium channel blockers.

“This study was post-market surveillance of drugs that had not been adequately evaluated in large, long-term clinical trials,” Psaty said.

Currently, Psaty and colleagues are studying the potential role of interactions between genes and drugs in the occurrence of cardiovascular events. They ask: Does a particular genetic susceptibility influence the effectiveness of a specific drug?

In one ongoing study, the investigators are looking at a drug used to treat people with high blood pressure. In about 30 percent of the population, Psaty explains, high blood pressure appears to be linked to a mutation in one of several genes associated with sensitivity to salt. People with this genetic variant are more sensitive to salt and have higher blood-pressure.

The researchers are asking what happens to patients with this genetic variant who are treated with diuretics, compared to people without the variant who are receiving the same treatment. Is diuretic therapy particularly effective in patients with this genetic variant?

The long-term goal, Psaty said, is to help clinicians tailor therapy. Some people on the treatment may do better with diuretics than others. Ultimately, researchers want to be able to separate these patients and develop the most effective treatments for each group.

Psaty said that when he joined the UW, he recognized Group Health Cooperative, now a partner in the CHRU, as a key player in these studies. One of the reasons is that the health maintenance organization’s computer records of patients include pharmacy data. Another is that the researchers realized they could put the computers to work screening massive amounts of information that would have taken years to screen by hand.

“As a young epidemiologist, I was struck by the tremendous opportunity to study drugs and their potential associations with cardiovascular disease outcomes,” Psaty said.

Psaty’s colleagues at Group Health Cooperative include Drs. Edward H. Wagner, professor of health services, and Andrea Z. LaCroix, professor of epidemiology.

Psaty received a Ph.D. in from Indiana University in 1979. He graduated from Indiana University School of Medicine in 1981 and received a master’s in public health in epidemiology from the UW in 1986. He was a Robert Wood Johnson Clinical Scholar between 1982 and 1986.

Psaty will discuss his research in detail in a Science in Medicine Lecture, titled “From Pharmacoepidemiology to Pharmacogenetics,” on Wednesday, Dec. 8, from noon to
1 p.m. in room T-625 of the Health Science Center.

Will Morton