Herz

, Volume 38, Issue 8, pp 868–880

Cabergoline use and risk of fibrosis and insufficiency of cardiac valves

Meta-analysis of observational studies
Original article

Abstract

Background

Therapy with ergot-derivative dopamine agonists (ergot-DAs) is suspected to cause or promote the development of insufficiency and regurgitation in previously normal cardiac valves. Thus, we conducted a systematic review and meta-analysis of the literature to determine whether administration of cabergoline, i.e., an ergot-DA used to treat Parkinson’s disease (PD) or hyperprolactinemia, is associated with an increased risk of valve regurgitation compared with pharmacological regimens not comprising ergot-DAs or with no therapy.

Methods

Observational studies were selected from the Pubmed and Embase databases. Studies had to have assessed the prevalence, odds, or risk of cardiac valve regurgitation in patients who underwent chronic treatment with cabergoline for PD or hyperprolactinemia compared with patients with the same diseases whose therapy did not include cabergoline or another ergot-DA. Separate meta-analyses were performed for PD and hyperprolactinemia patients.

Results

On the basis of five studies, 634 PD patients were taking cabergoline, while 9,120 PD patients were treated with dopa/dopamine decarboxylase inhibitor, alone or associated with a non-ergot DA. Valvular regurgitation of any degree—at one cardiac valve or more —was more frequent in PD patients who were taking cabergoline compared to those treated with a non-ergot DA agent or not treated with any dopamine agonist [adjusted (inverse variance: iv) odds ratio: 7.25 95 % CI: 3.71–14.18; p < 0.0001]. On the other hand, pooled data from seven studies showed that patients with hyperprolactinemia who were taking cabergoline (n = 444) exhibited significantly higher odds of mild- to-moderate tricuspid regurgitation compared to untreated controls (n = 954) [adjusted (iv) odds ratio: 1.92 95 % CI:1.34–2.73; p = 0.0003]. No significant differences in mitral or aortic valve regurgitation were detected between hyperprolactinemic patients taking cabergoline and controls.

Conclusion

In PD patients, the risk of valvular regurgitation of any grade involving one or more cardiac valves was proven to be strongly associated with cabergoline treatment. Furthermore, based on our results, hyperprolactinemic patients taking cabergoline have an increased risk of mild-to-moderate tricuspid valve regurgitation.

Keywords

Meta-analysis Parkinson’s disease Valvular regurgitation Fibrosis Cabergoline 

Cabergolingabe und Risiko einer Fibrose mit Herzklappeninsuffizienz

Metaanalyse von Beobachtungsstudien

Zusammenfassung

Hintergrund

Die Therapie mit Dopaminagonisten aus Ergotderivaten (Ergot-DAs) steht im Verdacht, die Entwicklung einer Insuffizienz und Regurgitation bei zuvor normalen Herzklappen zu verursachen oder auszulösen. Daher entschlossen wir uns zur Durchführung einer systematischen Übersichtsarbeit und Metaanalyse der Literatur, um zu ermitteln, ob die Gabe von Cabergolin, d. h. von einem Ergot-DA zur Behandlung der Parkinson-Krankheit oder der Hyperprolaktinämie, mit einem erhöhten Risiko der Klappenregurgitation im Vergleich zu medikamentösen Schemata ohne Ergot-DAs oder im Vergleich zu keiner Therapie einhergeht.

Methoden

Beobachtungsstudien wurden aus den Datenbanken Pubmed und Embase ausgewählt. In den Studien musste die Prävalenz, die Wahrscheinlichkeit oder das Risiko für eine Herzklappenregurgitation bei Patienten mit chronischer Cabergolinbehandlung wegen Parkinson-Krankheit oder Hyperprolaktinämie im Vergleich zu Patienten mit den gleichen Erkrankungen, aber ohne Therapie mit Cabergolin oder einem anderen Ergot-DA untersucht worden sein. Es wurden getrennte Metaanalysen für Parkinson- und Hyperprolaktinämiepatienten durchgeführt.

Ergebnisse

Grundlage waren 5 Studien, demnach nahmen 634 Parkinson-Patienten Cabergolin, 9120 Parkinson-Patienten wurden mit Dopa-/Dopamindekarboxylaseinhibitorpräparaten behandelt, allein oder mit einem Nicht-Ergot-DA kombiniert. Eine Klappenregurgitation jeglichen Grades – bei einer oder mehreren Herzklappen – war häufiger bei Parkinson-Patienten mit Cabergolintherapie als unter Therapie mit einem Nicht-Ergot-DA oder ganz ohne Dopaminagonist [adjustierte (inverse Varianz, IV) Odds Ratio: 7,25; 95 %-KI: 3,71–14,18; p < 0,0001]. Andererseits zeigten gepoolte Daten von 7 Studien, dass Patienten mit Hyperprolaktinämie unter Cabergolin (n = 444) eine signifikant höhere Wahrscheinlichkeit für eine leichte bis mittelgradige Trikuspidalklappenregurgitation im Vergleich zu unbehandelten Kontrollen aufwiesen [n = 954; adjustierte (IV) Odds Ratio: 1,92; 95 %-KI:1,34–2,73; p = 0,0003]. Ein signifikanter Unterschied hinsichtlich einer Mitral- oder Aortenklappenregurgitation stellte sich zwischen den Hyperprolaktinämiepatienten unter Cabergolin und den Kontrollen nicht heraus.

Schlussfolgerung

Bei Parkinson-Patienten war nachgewiesenermaßen das Risiko einer Klappenregurgitation jeglichen Grades mit Beteiligung einer oder mehrere Herzklappen stark mit einer Cabergolintherapie assoziiert. Außerdem besteht unseren Ergebnissen zufolge bei Hyperprolaktinämiepatienten mit Cabergolintherapie ein erhöhtes Risiko für eine leichte bis mittelgradige Trikuspidalklappenregurgitation.

Schlüsselwörter

Metaanalyse Parkinson-Krankheit Klappenregurgitation Fibrose Cabergolin 

Supplementary material

59_2013_3816_MO1_ESM.pdf (132 kb)
Appendix – summary of studies (PDF 0,1MB)

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Copyright information

© Urban & Vogel 2013

Authors and Affiliations

  1. 1.Cardiology Unit Presidio Sanitario Intermedio“Elena d’Aosta”NaplesItaly
  2. 2.Institute of Hygiene and Preventive MedicineSecond University of NaplesNaplesItaly

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