Long-term safety, tolerability and efficacy of combination therapy with aliskiren and amlodipine in patients with hypertension

ABSTRACT

Objective: Most patients with hypertension require antihypertensive combination therapy to achieve BP control. This study investigated the safety and efficacy of the direct renin inhibitor aliskiren combined with the calcium channel blocker amlodipine.

Methods: Overall, 556 patients with hypertension (msDBP ≥95−<110 mmHg) received open-label aliskiren/amlodipine 150/5 mg for 2 weeks, followed by forced titration to aliskiren/amlodipine 300/10 mg for 52 weeks. Add-on hydrochlorothiazide (HCT) was permitted from week 10 to achieve BP control (<140/90 mmHg). The primary objective of the study was to evaluate the long-term safety and tolerability of aliskiren/amlodipine combination therapy; the BP-lowering efficacy of the combination was also assessed (week 54 endpoint; last observation carried forward).

Results: In total, 452 patients completed 54 weeks’ treatment with aliskiren/amlodipine 300/10 mg, with or without add-on HCT. The most frequently reported adverse events (AEs) were peripheral edema, upper respiratory tract infection, headache and bronchitis. Peripheral edema (the most common AE), occurred in 22.7% of treated patients, and was generally mild or moderate in intensity and transient in nature. Few patients exhibited laboratory abnormalities. Aliskiren/amlodipine combination therapy provided a mean BP reduction from baseline to week 54 of 24.2/15.5 mmHg; 74.3% of patients achieved BP control. In the subgroup of patients with stage 2 hypertension (baseline msSBP ≥160 mmHg and/or msDBP ≥100 mmHg), the mean BP reduction at week 54 was 29.1/17.1 mmHg, and 67.0% of patients achieved BP control.

Conclusion: In this open-label study, aliskiren/amlodipine 300/10 mg combination therapy, with or without add-on HCT, effectively reduced BP, particularly in patients with stage 2 hypertension. The most common AE was peripheral edema, consistent with the known AE profile of high-dose (10 mg) amlodipine. Further studies comparing the aliskiren/amlodipine combination with the component monotherapies and other antihypertensive combinations are warranted.

Trial registration: ClinicalTrials.gov identifier: NCT00402103.

Key words: :

• Aliskiren
• Amlodipine
• Calcium channel blocker
• Combination drug therapy
• Direct renin inhibitor
• Hypertension
• Safety

Acknowledgments

Declaration of interest: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Y. Z. and W. L. are employees of Novartis Pharmaceuticals Corporation, and are thus eligible for Novartis stock and stock options. P. T. is a member of the German board of the ONTARGET/TRANSCEND study, is involved in Novartis clinical studies, and has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merckle-Recordati, Novartis, Solvay and Takeda. T. W. L and G. H. have no conflicts of interest to declare.

All authors participated in the development and writing of the paper, and approved the final manuscript. The authors take full responsibility for the contents of the article but thank Dr Jenny Handford (Oxford PharmaGenesis™ Ltd) for assistance in collating and incorporating comments from all authors to produce a final draft manuscript for submission. This medical writing assistance was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

List of principal investigators

Belgium: J Mortelmans, P Feys, F Heyvaert, G Hollanders, R Leliaert, A Pollet, E Schatteman, D Van Troyen, J Vernijns. Denmark: J Vinberg, R Christensen, N Gerdes, T Fogh-Andersen, S Mygind, S Wichmand, J Flintholm, A Høegholm. Finland: T Tikkanen, J Hopsu, P Pippola, P Kasemets, U Laisi, R Kaaja, J Strand, J Muusavi, I Kantola. Germany: H Benduhn, A Tat, K Droese, M Krueger, L Maiwald, M Rauch, J Hauptmann, R Rummel, G Stuchlik, H-P Unterberg, R Stern, I Senftleber, H Samer, W Rechl, M Stern, W Trs, R Franz. Iceland: G Thorgeirsson. India: U Rani, A Kumar, M Thomas. USA: G Balaji, A Carr, K Dexter, W Spisak, J Mallory, A Dallas, C Farrington, T McKnight, S Christiansen, M Borsheim, W Gray, S Cox, P Gibb, Y Sierra, D Huffman, W Smith, S Akbar, J Gabriel, S Jones, P Kumar, T Littlejohn, R Lipetz, N Lunde, J Austin, P Lane, J Brown, S Wilson, A Soo, J Vazquez-Tanus, S Rapo, T Rossiter, C Martorell, D Brautigam, T Herman, J Vasil, J Rhudy, J Williams, S Hippler. Switzerland: A Petrillo, H-J Bopp, C Ott, G Nager.