Feb. 26, 2004 -- Epidemiologist Klim McPherson, PhD, says he was lampooned and largely ignored when he warned that hormone replacement therapy increased heart disease risk -- five years before a huge prevention trial was halted early for the same reason.
The British researcher now says the hormone replacement therapy (HRT) experience could happen again unless drug manufacturers are required to change the way they report clinical trials. He wants government regulators to require the companies to record all adverse events when they conduct clinical studies and make all their results public. His commentary is published in the Feb. 28 issue of the British Medical Journal.
"If that had happened in this case, we would have known much earlier of the real effect that HRT has on coronary heart disease risk," he tells WebMD.
More Harm Than Good
It has been just over a year and a half since millions of postmenopausal women learned that the hormone therapy they were taking to lower their risk of heart disease and other diseases of aging might be doing them more harm than good. That was when a major government trial, known as the Women's Health Initiative (WHI), linked the long-term use of combined estrogen and progestin as menopausal hormone therapy to an increased risk of heart disease, as well as stroke and breast cancer.
Five years earlier, McPherson and colleagues raised the red flag about hormone replacement therapy and heart disease after analyzing 23 pharmaceutical-industry trials involving some 3,300 women. Instead of finding a 50% reduction in heart disease risk for women taking HRT, as observational studies suggested, the combined data indicated a 40% increase in risk.
"When we published these findings we were ridiculed by people who said the trials we used were inadequate and the follow-up times were too short," McPherson says. "We then began looking for unpublished trials to add to our findings."
The researchers found six such trials that had appropriate designs, involving 640 women, but they had to win a court battle with the drug companies that conducted them to gain access to the findings. The six studies showed an even stronger link between HRT use and heart disease risk.
Combined data from all the industry studies showed an increase in heart disease risk that was identical to that reported later for the first year of use in the WHI trial.
"The 29 trials we assessed were the only ones among about 200 trials conducted by drug companies in which adverse events were recorded," he says. "Companies that submit applications to regulatory agencies for the licensing of new drugs should be required to record these events and make them public."
Other Studies Questioned Benefits
Wake Forest University cardiology professor David Herrington, MD, agrees that drug companies should make their clinical trial safety data available to the public. But he adds that there were plenty of non-industry studies that questioned the cardiovascular benefits of HRT prior to the publication of the WHI findings.
The year after McPherson and colleagues reported their findings, a large government study showed that hormone replacement therapy increased heart attack risk during the first year of use in women with a history of heart disease. Herrington says many other studies published over the next few years showed either no cardiovascular benefit for HRT or clear evidence of harm.
"Long before WHI, the cardiovascular risks vs. benefits of HRT were being hotly debated within the medical community," Herrington tells WebMD. "Many people were highly critical of the negative studies because they went against the prevailing paradigm that HRT protected the heart. But eventually there was a critical mass of evidence that was contrary to this paradigm, which prompted a sea change in opinion."