Antihypertensive efficacy and tolerability of aliskiren/hydrochlorothiazide (HCT) single-pill combinations in patients who are non-responsive to HCT 25 mg alone^*

ABSTRACT

Objective: Thiazide diuretics such as hydrochlorothiazide (HCT) are a widely used first-line treatment for hypertension, but most patients will not achieve blood pressure (BP) control with HCT alone and so will require combination therapy. In this study the efficacy, safety and tolerability of a single-pill combination (SPC) of the direct renin inhibitor aliskiren with HCT were investigated in patients non-responsive to HCT 25 mg therapy.

Methods: In this study, 722 patients with hypertension and an inadequate response to 4 weeks of HCT 25 mg (mean sitting diastolic BP ≥90 and <110 mmHg) were randomized to once-daily, double-blind treatment for 8 weeks with an SPC of aliskiren/HCT 300/25 mg or 150/25 mg, or continued HCT 25 mg monotherapy. Least-squares mean changes in mean sitting systolic/diastolic BP (msSBP/DBP) from double-blind baseline were analyzed for the ITT population at week 8 endpoint.

Results: Aliskiren/HCT 300/25 mg and 150/25 mg SPCs lowered msSBP/DBP from baseline by 16.7/10.7 and 12.9/8.5 mmHg, respectively, both significantly greater reductions than HCT 25 mg alone (7.1/4.8 mmHg; both p < 0.001). Rates of BP control (<140/90 mmHg) were also significantly higher with aliskiren/HCT 300/25 mg (58%) and 150/25 mg (49%) than with HCT (26%; both p < 0.001). Aliskiren/HCT 300/25 mg provided significantly greater msSBP/DBP reductions and rates of BP control than the 150/25 mg SPC dose (all p < 0.05). Aliskiren/HCT SPC treatment showed similar tolerability to HCT alone and a numerically lower incidence of hypokalemia (serum potassium <3.5 mmol/L; aliskiren/HCT, 1.3–2.2%: HCT alone, 3.4%).

Conclusion: Aliskiren/HCT SPCs provide clinically significant BP reductions and improved BP control rates in patients who are non-responsive to HCT 25 mg monotherapy. Limitations of the study were the mainly Caucasian patient population and the non-responder design.

Key words: :

• Aliskiren
• Direct renin inhibitor
• Hydrochlorothiazide
• Hypertension
• Non-responder
• Single-pill combination

Acknowledgments

Declaration of interest: This study was funded by Novartis Pharmaceuticals Corporation.

G. I., Z. L. and J. Z. are employees of Novartis Pharmaceuticals, and are therefore eligible for Novartis stock and stock options. M. B., J. R., A. C. and K. A. have no conflicts of interest to declare.

M. B., J. R., A. C. and K. A. participated in the design of the study and in the writing of the study protocol, approved the final protocol, participated in the collection, analysis, and interpretation of data, and in the writing of the manuscript, and approved the final manuscript. G. I., Z. L. and J. Z. 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 and in the writing of the manuscript, and approved the final manuscript.

The authors take full responsibility for the contents of the paper but thank Dr Ann Taylor (Oxford PharmaGenesis™ Ltd) for assistance in collating and incorporating comments from all authors and editing the final manuscript; this work was funded by Novartis.

List of principal investigators: Denmark: O. Pedersen; B. Uhrenholt; P. Kristiansen; P. Schultz; M. Lytje; A. Høegholm; K. Ginger-Mortensen; L. Sterndorff; K. Christensen; A. Axelsen; S. Garne; G. Jensen. Finland: T. Pehkonen; R. Mauno; R. Gronfors; P. Järvinen; P. Meriranta; P. Järvinen; V-P. Harjola. Germany: A. Trostorff; C. Barho; H. Benduhn; R. Bodenschatz; B. Drewelow; W. Faust; U. Gerbaulet; V. Henning; C. Hinrichs; T. Hoch; M. Huptas; J. Jordan; M. Kiper; K. Kleinertz; R. Kniewel; M. Loddo; G. Mahla; F. Missel; S. Moeller; E. Mueller; E. Parsi; M. Schaper; S. Laus; L. Schulze; J. Stockhausen; A. Wagner; J. Weimer; K. Zitzmann; G. Fahron; G. Schirmeister; K. Haase; F. Bannout; H-G. Weber; M. Kuhrs; R. Brandstetter; G. Scholz; K. Seifert; J. Chevts; A. Himpel-Boenninghoff; H. Arievich; S. Mager; A. Linnhoff; T. Wende. Hungary: P. Torzsa; M. Dudas; E. Fabian; H. Bela. Iceland: B. Thorsson. India: R. Cama; V. Gowda; M. Naidu; J. Ramapuram. Netherlands: T. Boermans; W. Feis; H. Fransen; A. Kiel; H. Mevissen; W. Veerman; M. Willink; W. Spiering; A. Apperloo; P. van Leeuwen; A. Lambregts. Poland: M. Galewicz; M. Mierzejewski; K. Jacewicz; A. Kowalisko; M. Rozycka-Grudniewicz. Slovakia: D. Foldiova; L. Csala; T. Duris; S. Haeberleova; K. Benova. Spain: C. Brotons; A. Ibañez; X. Sanchez; M. Guiu; B. Queipo; G. Tamborero; M. Sas; J. Eizaguirre; M. Jimenez; C. Gracias; V. Aragüe; M. Oltra; L. Ezpeleta; J. Enriquez; C. Alvarez.

Notes

* These results have been presented at the 23rd Meeting of the American Society of Hypertension, New Orleans, USA; 14 – 17 May 2008; and at the 22nd Meeting of the International Society of Hypertension and the 18th Meeting of the European Society of Hypertension, Berlin, Germany; 14–19 Jun 2008