Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study

Abstract

AimsAn anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM.Methods and resultsIn this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died.ConclusionBromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.Clinical trial registrationClinicalTrials.gov, study number: NCT00998556.

Marked Vascular Dysfunction in a Case of Peripartum Cardiomyopathy

“…We speculate that the observed coronary artery dysfunction resulted in myocardial underperfusion and compromised reactive hyperemia, especially during the peripartum phase of marked hormonal and metabolic changes, possibly leading to ischemic insult to the myocardium and subsequent myocardial dysfunction. This might explain in part why early treatment with bromocriptine, a dopamine agonist known to vasodilate, resulted in an improved outcome of PPCM [9]. …”

Peripartum cardiomyopathy

“…A recent randomized trial of 63 German women with PPCM that compared one week and eight week regimens of bromocriptine found similar improvements in LVEF 136. No women died or required LVAD or transplantation.…”

“…Notably, two cases of venous thromboembolism and one case of peripheral arterial thrombosis occurred despite the use of prophylactic anticoagulation. No placebo group was included because this was thought to be unethical given the pilot data, but the authors noted that 23 of 37 women with baseline LVEF <30% recovered to an LVEF ≥50% compared with 10 of 27 women with a baseline LVEF <30% in the IPAC cohort (of whom only one received bromocriptine) 136. The different racial compositions of the study populations (only one woman was black in the German trial compared with 30 women in IPAC) limits direct comparison of these study outcomes 136.…”

“…No placebo group was included because this was thought to be unethical given the pilot data, but the authors noted that 23 of 37 women with baseline LVEF <30% recovered to an LVEF ≥50% compared with 10 of 27 women with a baseline LVEF <30% in the IPAC cohort (of whom only one received bromocriptine) 136. The different racial compositions of the study populations (only one woman was black in the German trial compared with 30 women in IPAC) limits direct comparison of these study outcomes 136. Of note, 72% of women in the IPAC cohort overall recovered to an LVEF ≥50% without the use of bromocriptine 76…”

“…Some experts and clinical investigators advocate for bromocriptine as part of the management of all women with PPCM,136150 whereas others advise breast feeding for all women who are stable enough to do so, citing fetal benefit and lack of evidence of harm to the mother 13117151. As discussed above, until further data are available, it would be reasonable to consider the use of bromocriptine in women with severe left ventricular dysfunction (eg, LVEF <25%) or cardiogenic shock.…”