Recent in vitro findings of negative inotropy of pantoprazole did not translate into clinically relevant effects on left ventricular function in healthy volunteers

Wolfgang Schillinger, Nina Hörnes, Nils Teucher, Samuel Sossalla, Daniel Sehrt, Klaus Jung, Mark Hünlich, Bernhard Unsöld, Bianca Geiling, Giuliano Ramadori, Reinhard Hilgers, Harald Schwörer, Gerd Hasenfuss, Wolfgang Schillinger, Nina Hörnes, Nils Teucher, Samuel Sossalla, Daniel Sehrt, Klaus Jung, Mark Hünlich, Bernhard Unsöld, Bianca Geiling, Giuliano Ramadori, Reinhard Hilgers, Harald Schwörer, Gerd Hasenfuss

Abstract

Purpose: Reports on cardiac problems with oral proton pump inhibitors have caused extensive safety reviews by the US Food and Drug Administration. We provide additional data on acute cardiac effects of an intravenous application.

Methods: Echocardiography was performed in 18 healthy volunteers after administration of a common high-dose regimen of pantoprazole (80 mg i.v. bolus followed by 8 mg/h for 1 h) or placebo.

Design: The design included a randomized, double-blind, placebo-controlled cross-over trial.

Results: Ejection fraction (%, mean +/- SE) in the treatment group (placebo group) was 60.7 +/- 1.1 (61.2 +/- 1.7) at baseline, and 62.6 +/- 1.1 (62.1 +/- 1.9), 64.7 +/- 1.6 (63.5 +/- 1.3), 62.6 +/- 1.6 (61.0 +/- 1.6) and 63.0 +/- 1.4 (61.8 +/- 1.5) at 7.5, 15, 30 and 60 min after bolus application, respectively (p = n.s.). Similarly, no significant changes were found for cardiac output, cardiac index, blood pressure and heart rate. In contrast, gastric pH that was used as a treatment control was significantly increased 60 min after the application of pantoprazole as compared to baseline and to placebo.

Conclusions: Pantoprazole as injection is safe in healthy subjects with respect to cardiac contractile function. However, in view of recent reports of negative inotropy of the drug, further studies in heart failure patients are required.

Figures

Fig. 1
Fig. 1
Flowchart of participation in the study
Fig. 2
Fig. 2
Mean ± SE of systolic and diastolic blood pressure (a) and of heart rate (b) at baseline (BL) and during application of a pantoprazole high-dose regimen (cf. “Materials and methods”) as compared to placebo (n = 18 each)
Fig. 3
Fig. 3
Original recordings of typical gastric pH profiles of a healthy subject under treatment with pantoprazole (a) or placebo (b). cBoxandwhiskers plots showing median pH and 25–75% quartiles of gastric pH in healthy volunteers under treatment with pantoprazole or placebo at baseline (BL) and after 60 min. Outliers are marked with circles (n = 18 each)

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