VIENNA — The dopamine agonist bromocriptine shows considerable promise for the treatment of peripartum cardiomyopathy, Dr. Olaf Forster said at the annual congress of the European Society of Cardiology.
“The results obtained by the addition of bromocriptine to standard heart failure treatment in this study are encouraging. Bromocriptine may represent a novel therapeutic approach in the treatment of peripartum cardiomyopathy, but the data need to be considered as preliminary,” according to Dr. Forster of the University of the Witwatersrand, Johannesburg, South Africa.
The hallmark of peripartum cardiomyopathy (PPCM) is onset of left ventricular failure between 1 month before and 5 months after delivery. The highest rates of PPCM in the world are reported in South Africa. “We get two or three new patients per week in Soweto,” said Dr. Forster, who is with the university's cardiovascular research unit at the Chris Hani Baragwanath Hospital, Soweto.
Treatment of PPCM involves standard heart failure medications and firm advice to avoid further pregnancies. A subsequent pregnancy can be fatal; half of women who become pregnant again after a first episode of PPCM experience long-term worsening of heart failure, whereas the other half return to their normal prepregnancy left ventricular systolic function.
Dr. Forster reported on 16 indigenous black women ages 26–39 with PPCM who presented with a subsequent pregnancy 1–6 years following their index PPCM pregnancy. The first six women—the control group—didn't receive bromocriptine because their pregnancies occurred before the South African team learned of evidence from German studies in knockout mice suggesting that the drug might be beneficial in PPCM. The next 10 patients received bromocriptine at 2.5 mg b.i.d. for 2 months beginning 4 hours post delivery. This was the first study of the drug in human PPCM.
All 16 patients were on a diuretic and β-blocker during pregnancy, with an ACE inhibitor added post partum.
The mean left ventricular ejection fraction in controls was 44% at baseline, declining to 36% at 1 month post partum and to 25% 3 months post partum. In contrast, the baseline ejection fraction was 51% in the bromocriptine-treated group, dropping to 43% 1 month post partum, and rebounding to 55% by 3 months post partum.
At 3 months post partum, 2 of 6 controls were dead of heart failure, compared with none of the 10 women who received bromocriptine.
Bromocriptine had no side effects, but some women on the prolactin inhibitor were quite disturbed that they couldn't breast feed, according to Dr. Forster.
In the STAT3 female knockout mouse model of PPCM, enhanced postpartum oxidative stress results in cathepsin D-facilitated cleavage of the 23-kd form of prolactin into its 16-kd form, which is proapoptotic and antiangiogenic. This short-form prolactin disrupts endothelial cell function and promotes vasoconstriction, resulting in impaired cardiac microcirculation, increased cardiac apoptosis, and reduced postpartum survival. Bromocriptine prevents PPCM in this model.
Session cochair Dr. Robert Califf, vice-chancellor for clinical research, director of the Translational Medicine Institute, and professor of medicine at Duke University, Durham, N.C., called the clinical results encouraging, but wondered why the investigators hadn't mounted a randomized trial. Dr. Forster replied that the risks posed by subsequent pregnancy in women with PPCM are so great that he and his coworkers believe it would be unethical to deny them bromocriptine. “The risk is simply too high—and we can see that it works,” he explained.
However, a randomized trial is ongoing in women experiencing a first episode of PPCM, Dr. Forster added.