AIM: ICDs do not reduce mortality risk for women with heart failure
Implantable cardioverter defibrillators (ICDs) do not appear to be associated with a reduced risk of death in women with advanced heart failure, according to a meta-analysis in Monday’s issue of Archives of Internal Medicine.
Heart failure affects about 5.3 million U.S. patients, almost half of them women, according to the authors. Patients with heart failure are six to nine times more likely than the general population to experience sudden cardiac death. In addition to medication, treatment for heart failure involves preventing sudden cardiac death through the implantation of a cardioverter defibrillator. This therapy is supported by numerous clinical trials, the authors noted; however, questions remain regarding the benefits in certain patient subgroups, including women.
Hamid Ghanbari, MD, and colleagues at Providence Hospital Heart Institute and Medical Center in Southfield, Mich., searched for randomized clinical trials of implantable defibrillator therapy for heart failure patients published between 1950 and 2008 that included data on the risk of death for female patients. They identified five eligible trials that included 934 women.
According to the researchers, none of the five trials demonstrated a significant benefit of defibrillator implantation over medical therapy for women. When they pooled the data and performed a meta-analysis, the ICD was not associated with decreased all-cause mortality in women. Among the 3,810 men in the studies, however, a statistically significant decrease in death rate was found in each of the five trials alone and in the combined meta-analysis.
There are several possible reasons for the sex differences in these results, the authors noted. Among patients with heart disease, women have about one-fourth the risk of sudden cardiac death as men. This may be because women have different patterns of arrhythmias and also because they have more co-occurring illnesses that may increase their risk of death from other causes.
Therefore, the researchers said that a larger study population may be needed to show any benefit of defibrillator implantation in women.
"Most clinical trials have been heavily weighted toward men; therefore, generalization of the results to women remains questionable. The best answer to this problem would be to perform a clinical trial that specifically targets women with heart failure to test the hypothesis of whether ICD implantation reduces their overall mortality rate," the authors concluded.
Because clinical guidelines already recommend defibrillator treatment to prevent sudden cardiac death, such a trial may be difficult to propose, they noted. "However, on the basis of our findings it seems that a trial targeting women is needed, and a meta-analysis such as ours may be an appropriate first step to explore this hypothesis," Ghanbari and colleagues wrote.
In an accompanying editorial, Rita F. Redberg, MD, of University of California, San Francisco, and the editor of Archives of Internal Medicine, said that approximately 30 percent of ICD recipients are women. “However, data supporting the efficacy of ICDs for primary prevention in women is sparse," she wrote. "In other words, ICDs are being implanted in hundreds of thousands of women without substantial evidence of benefit, apparently based on the assumption that, to paraphrase the old saying, 'What's good for the gander is good for the goose.'"
"It is important to know the benefits of implantable cardioverter defibrillator use in women, especially considering the known risks of morbidity and mortality," Redberg continued. "Ghanbari et al rightly conclude that further studies are needed. Part of the reason for the lack of sex-specific data for devices may be related to the lack of FDA guidance in this area. There is reason to be optimistic that this deficit will start to be corrected in the near future."
"Until then, meta-analyses such as the one by Ghanbari et al are the best way to determine if the goose is doing as well as the gander," she concluded.
Heart failure affects about 5.3 million U.S. patients, almost half of them women, according to the authors. Patients with heart failure are six to nine times more likely than the general population to experience sudden cardiac death. In addition to medication, treatment for heart failure involves preventing sudden cardiac death through the implantation of a cardioverter defibrillator. This therapy is supported by numerous clinical trials, the authors noted; however, questions remain regarding the benefits in certain patient subgroups, including women.
Hamid Ghanbari, MD, and colleagues at Providence Hospital Heart Institute and Medical Center in Southfield, Mich., searched for randomized clinical trials of implantable defibrillator therapy for heart failure patients published between 1950 and 2008 that included data on the risk of death for female patients. They identified five eligible trials that included 934 women.
According to the researchers, none of the five trials demonstrated a significant benefit of defibrillator implantation over medical therapy for women. When they pooled the data and performed a meta-analysis, the ICD was not associated with decreased all-cause mortality in women. Among the 3,810 men in the studies, however, a statistically significant decrease in death rate was found in each of the five trials alone and in the combined meta-analysis.
There are several possible reasons for the sex differences in these results, the authors noted. Among patients with heart disease, women have about one-fourth the risk of sudden cardiac death as men. This may be because women have different patterns of arrhythmias and also because they have more co-occurring illnesses that may increase their risk of death from other causes.
Therefore, the researchers said that a larger study population may be needed to show any benefit of defibrillator implantation in women.
"Most clinical trials have been heavily weighted toward men; therefore, generalization of the results to women remains questionable. The best answer to this problem would be to perform a clinical trial that specifically targets women with heart failure to test the hypothesis of whether ICD implantation reduces their overall mortality rate," the authors concluded.
Because clinical guidelines already recommend defibrillator treatment to prevent sudden cardiac death, such a trial may be difficult to propose, they noted. "However, on the basis of our findings it seems that a trial targeting women is needed, and a meta-analysis such as ours may be an appropriate first step to explore this hypothesis," Ghanbari and colleagues wrote.
In an accompanying editorial, Rita F. Redberg, MD, of University of California, San Francisco, and the editor of Archives of Internal Medicine, said that approximately 30 percent of ICD recipients are women. “However, data supporting the efficacy of ICDs for primary prevention in women is sparse," she wrote. "In other words, ICDs are being implanted in hundreds of thousands of women without substantial evidence of benefit, apparently based on the assumption that, to paraphrase the old saying, 'What's good for the gander is good for the goose.'"
"It is important to know the benefits of implantable cardioverter defibrillator use in women, especially considering the known risks of morbidity and mortality," Redberg continued. "Ghanbari et al rightly conclude that further studies are needed. Part of the reason for the lack of sex-specific data for devices may be related to the lack of FDA guidance in this area. There is reason to be optimistic that this deficit will start to be corrected in the near future."
"Until then, meta-analyses such as the one by Ghanbari et al are the best way to determine if the goose is doing as well as the gander," she concluded.