Dataset Information

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

ABSTRACT:

Aims

An 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 results

In 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.

Conclusion

Bromocriptine 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 registration

ClinicalTrials.gov, study number: NCT00998556.

SUBMITTER: Hilfiker-Kleiner D

PROVIDER: S-EPMC5837241 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Right ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement. METHODS:In this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF?<?45%). We examined the effect of short-term (1W: bromocriptine, 2.5 mg, 7 days, n?=?10) compared with long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for another 6 weeks, n?=?14) in addition to guideline-based heart failure therapy in patients with an initial RVEF?<?45% on the following outcomes: (1) change from baseline (? delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF???50%) and (4) rate of patients with full RV recovery (RVEF???55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging. RESULTS:Reduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p?=?0.027). RVEF increased from 38?±?7 to 53?±?11% with a delta-RVEF of +?15?±?12% in the 1W group, and from 35?±?9 to 58?±?7% with a ? RVEF of +?23?±?10% in the 8W group (? RVEF 1W vs 8W: p?=?0.118). LVEF increased from 25?±?8 to 46?±?12% with a ? LVEF of +?21?±?11% in the 1W group, and from 22?±?6 to 49?±?10% with a ? LVEF of +?27?±?9% in the 8W group (? LVEF 1W vs 8W: p?=?0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p?=?0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p?=?0.092). CONCLUSIONS:Despite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment.

Project description:Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size.The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM.This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months.This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM.ClinicalTrials.gov Identifier: NCT00998556.