Second Verse of HERS Same as the First— No Clear Benefit or Harm for Cardiovascular Disease
The Heart and Estrogen/Progestin Replacement Study (HERS) began with a simple premise: Despite the widespread use of hormone replacement therapy as a heart disease preventive in postmenopausal women with coronary heart disease, no blinded, placebo-controlled clinical trial had ever proved its value beyond a doubt. To the surprise of many, HERS proved a negative—that the treatment had no cardiovascular benefit in these women.
In this issue of Circulation (Circulation. 2002;105:917–922), Curt D. Furberg, MD, PhD, a professor at Wake Forest University School of Medicine (Winston-Salem, NC), and his colleagues at Wake Forest, the University of California (San Francisco), the Chicago Center for Clinical Research, and Emory University School of Medicine (Atlanta, Ga), analyzed the subgroup data from the 2763 postmenopausal women with coronary heart disease enrolled in HERS and again found no clear effect. They identified 86 post hoc subgroup variables. A few of the groups indicated that there might be a trend one way or the other, but when the results were carefully examined, the authors observed:
“Under the assumption of no effect of hormone treatment and given the 86 subgroup analyses, by chance, 4 comparisons would be expected to have a value of P≤0.05 in the 1-year analyses, and another 4 would be expected to have a value of P≤0.05 in the overall analyses. Thus, the fact that we observed 6 nominally significant interactions in the first year and 3 in the overall trial is almost exactly what would have been expected by chance if none of the 172 subgroups tested represented real interactions. This is not surprising, inasmuch as true subgroup interactions are rarely observed in clinical trials. It is important to underscore that most clinical trials have limited power for discovering statistically significant interactions.”
They did add, however, “The more plausible findings of these subgroup analyses from HERS ought to be considered as hypothesis-generating and should be tested in ongoing and future trials.”
An accompanying editorial, by Elizabeth Barrett-Connor, MD, of the University of California at San Diego (Circulation. 2002;105:902–903), noted that “at the beginning of the Heart and Estrogen/Progestin Replacement Study (HERS), a secondary prevention trial of estrogen in postmenopausal women with heart disease, several experts opined that this trial was unnecessary at best and unethical at worst, given the consistency of the observational data, which certainly looks very impressive in a meta-analysis, and the plethora of potential cardioprotective mechanisms for estrogen that have been demonstrated in vivo and in vitro.”
A Little Cold Helps?
More than 225 000 Americans die each year from out-of-hospital cardiac arrest, and a similar number succumb in Europe. Two studies in the February 21, 2002, issue of the New England Journal of Medicine found therapeutic value for the use of slight hypothermia in the treatment of comatose cardiac arrest survivors. Both research groups—one in Europe and the other in Australia—found that when the body temperatures of such patients were lowered to 33°C for 12 to 24 hours, there was “impressive improvement in the neurologic outcome,” according to a perspective written by New England Journal of Medicine Editor Gerald D. Curfman, MD (N Engl J Med. 2002;346:546OpenUrlCrossRefPubMed).
He pointed out, however, that although the two studies were confirmatory of the benefit, “given the magnitude and complexity of the clinical problem, further studies of the efficacy and safety of therapeutic hypothermia in survivors of cardiac arrest should be given a high priority.”
The Australian team, led by Stephen A. Bernard, MB, BS of the Intensive Care Unit at Dandenong Hospital in Dandenong, Australia, found that 21 of 43 patients treated with hypothermia survived and were discharged home or to a rehabilitation facility, whereas only 9 of 34 patients whose temperatures were not lowered had a similar outcome (N Engl J Med. 2002;346:557–563OpenUrlCrossRefPubMed). The adjusted odds ratio for a good outcome with hypothermia as compared to normothermia was 5.25, they said. “However, the mechanism by which hypothermia may be beneficial is uncertain.”
In a larger study, the European Hypothermia after Cardiac Arrest Study group found that 75 of 136 patients in the hypothermia group for whom data were available had a favorable neurological outcome, whereas only 54 of 137 in the normothermia group had a similar outcome. At 6 months, mortality was 41% in the hypothermia group and 55% in the normothermia group.
The authors wrote, “Treatment with hypothermia may be of value in terms of public health. Each year, cardiac arrest occurs in approximately 375 000 people in Europe, about 30 000 of whom would meet our inclusion criteria. We can be 95% confident that treatment with hypothermia would prevent an unfavorable neurologic outcome in 1200 to 7500 of these patients.”
2.2 Million Americans Lost Health Insurance in 2001
The issue of access to health care came to the fore on February 12, 2002, when new figures showed that at least 2.2 million Americans had lost their health insurance in the previous year, the largest such increase in the uninsured in a decade.
A coalition of diverse organizations that ranged from the US Chamber of Commerce to the American Medical Association to the American Federation of Labor–Congress of Industrial Organizations (AFL-CIO) banded together to draw attention to the issue and call for action. They hope to bring pressure on Congress to expand health coverage to more Americans. However, their movement did not address the issue of how to accomplish that goal because the groups had differing views on the subject.
In the year 2000, the US Census Bureau estimated that 39 million Americans lacked health coverage, but that number jumped to at least 41.2 million in 2001. Job loss was the major cause behind loss of insurance, said Ron Pollack, executive director of the advocacy group Families USA. “Approximately one-half of this increase occurred in the period from September through December, thereby reflecting the impact of September 11,” he said. “The number of uninsured Americans now exceeds the cumulative populations of 23 states plus the District of Columbia.”
“These numbers, however, only paint part of the picture about America’s uninsured. The most poignant parts of the picture are the millions of people and families who are deferring unaffordable, needed health care—often with tragic results. Certainly, we can do much, much better—and we must,” he said.