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Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

Journal of Human Hypertension volume 24, pages 93–103 (2010)Cite this article

Abstract

Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) ⩾85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo (‘missed dose’) on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P⩽0.008). Loss of BP-lowering effect with aliskiren in the 24 h after a missed dose (1.0/0.7 mm Hg for 24–48-h vs 0–24-h MASBP/MADBP) was significantly lower than with irbesartan (3.6/2.2 mm Hg, P<0.01) or ramipril (4.0/2.6, P<0.0001). This equates to maintenance of 91/91% of the MASBP/MADBP-lowering effect with aliskiren, greater than irbesartan (73/77%) or ramipril (64/65%). The incidence of adverse events was similar across treatments (32.9–36.0%), although ramipril treatment was associated with an increased incidence of cough (ramipril, 6.1%; aliskiren, 0.5%; irbesartan, 1.8%). Aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24–48 h period after dose than irbesartan 300 mg or ramipril 10 mg.

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Acknowledgements

PP, WJ and ES participated in the writing of the study protocol, approved the final protocol, participated in the collection, analysis and interpretation of data as well as in the writing of the paper, and also approved the final paper. JB, CB and DLK participated in the design of the study and in the writing of the study protocol, approved the final protocol, supported the undertaking of the study, participated in the analysis and interpretation of the data as well as in the writing of the paper, and also approved the final paper. The authors take full responsibility for the content of the paper but thank Dr Richard White (Oxford PharmaGenesis™ Ltd) for assistance in collating the comments of the authors and editing the final paper. This work was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy

    P Palatini

  2. Department of Cardiology, Academic Hospital Villingen, Villingen-Schwenningen, Germany

    W Jung

  3. Scientific Research Institute of Cardiology, Saint Petersburg, Russia

    E Shlyakhto

  4. Novartis Pharma AG, Basel, Switzerland

    J Botha

  5. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    C Bush & D L Keefe

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  1. P Palatini
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  6. D L Keefe
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Corresponding author

Correspondence to P Palatini.

Appendix

Appendix

List of principal investigators

Brazil: Heno F Lopes, Osvaldo Kohlmann, Andrea Brandao, Virginia de Abreu, Lilian da Costa, Mario Torus Neves; Canada: Guy Chouinard, Guy Tellier, John Li, Brian Zidel, John C Fulop, Frederick F Jardine; Germany: Claudia Ulbrich, Reiner T Lehmann, Eberhardt Meier, Bjoern Paschen, Peder-Lars Stahnke, Eva Borbas, Hilmar Boeneke, Ernst Radermacher, Claus-Werner Blauth, Anton Strobel, Eckhard Massmann, Juergen Merke, Sigrid Gessner, Hans-Joachim Ulmer, Josef Junggeburth, Ludger Luetticke; Hungary: Tamas Forster, Janos Penzes, Judit Simon, Akos Kalina, Denes Pall, Emoke Csupor; Italy: Lucio Mos, Paolo Palatini, Flavio Scanferla, Valter Donadon, Massimo Santonastaso, Mario Sprovieri, Roberto Fogari, Natale Antonio Varì, Enrico Agabiti-Rosei, Roberto Pedrinelli, Maurizio Destro, Antonio Vinciguerra, Giuseppe Lembo, Claudio Ferri, Giuseppe Licata, Pier Giuseppe Agostoni, Giuseppe Guzzardi, Raffaele De Caterina, Claudio Borghi; Netherlands: Hans Prak, Peter Coenen, Harry Van Mierlo, AFE Bots, Hugo Rol, Robertus Costongs, Paulus Meurs, Willibrordus de Backer, Adriaan de Jong; Norway: Jørn Gronert, Asgeir Græsdal, Hans Olav Høivik, Sigbjørn Elle, Lasse G Gøranson, Dan Nørager, Charlotte Jacobsen, Russia: Eugene Shlyakhto, Inna Brodskaya, Tatiana Tyurina, Elena Baranova, Tatiana Novikova, Marina Balliuzek; Slovakia: Jan Murin, Jozef Semetko, Dagmar Okalova, Mikulas Szakacs, Viliam Bugan, Marian Snincak; Spain: Isabel Irizar, Ander Larrazabal, Francisco Valls Roca, Jose L Lafuente, Ana Puertas, Jose Abellan Aleman, Fernando Hernandez, Josefina Olivan, Pablo Gomez, Antonio Ortega, Carlos Calvo Gomez, Josep Lluis Fernandez Roure, Arturo Saenz Fernandez, Isidro Lopez, Jose A Dura Garcia, Jose Tolosana.

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Palatini, P., Jung, W., Shlyakhto, E. et al. Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study. J Hum Hypertens 24, 93–103 (2010). https://doi.org/10.1038/jhh.2009.38

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