Aliskiren added to ACE, ARB Therapy causes higher adverse events

On December 20, 2011 in Basel, Switzerland; Novartis announced that the data safety and monitoring board (DSMB) for the ALTITUDE trial identified an increase in adverse events and no apparent benefit among patients randomized to aliskiren (Rasilez/Tekturna, Novartis), thus prompting their recommendation for termination of the study.

The ALTITUDE trial tried "to determine whether, in patients with type 2 diabetes and pre-existing disease of the heart and the circulatory system and/or the kidney, aliskiren at a target dose of 300 mg once daily (compared to placebo), on top of conventional treatment, reduces death and disease caused by the heart, the circulatory system and the kidney."

Simply put, the trial was studying aliskiren on top of ACE-inhibitor or angiotensin-receptor-blocker (ARB) therapy in patients with type 2 diabetes and renal impairment compared with a placebo add-on.

Novartis Headquarters in Basel Switzerland

In making its recommendation, the DSMB noted that the active-treatment group experienced an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension over 18 to 24 months of follow-up. The committee concluded that patients were unlikely to benefit from aliskiren on top of standard antihypertensive therapy.

"Novartis is in ongoing discussions with health authorities worldwide about the implications of the findings from ALTITUDE for patients," a press release reads. "As a precautionary measure, Novartis will cease promotion of Rasilez/Tekturna-based products for use in combination with an ACE inhibitor or ARB."

The company is also checking in with the DSMBs of other clinical studies studying aliskiren alone or in combination.

ALTITUDE investigators are being told to remove aliskiren from their patients' treatment regimen and review their current blood-pressure medications; patients in ALTITUDE are advised to contact their doctors.

Earlier that same year (in 2011), positive results of the ACCELERATE trial looking at aliskiren in combination with a calcium-channel blocker were published in the Lancet. A year before this (in 2010) the FDA approved both a dual- and triple- combination drug including aliskiren, but neither drug included an ACE inhibitor or ARB.

About Novartis
Novartis International AG is a Swiss multinational pharmaceutical company based in Basel, Switzerland, ranking number two in sales (46.806 billion US$) among the world-wide industry in 2010.

Reference(s):

1. Novartis. Novartis announces termination of ALTITUDE study with Rasilez/Tekturna in high-risk patients with diabetes and renal impairment [press release]. December 20, 2011. Available at http://www.novartis.com/newsroom/media-releases/en/2011/1572562.shtml
2. Norvatis. Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints (ALTITUDE): ClinicalTrials.gov/NCT00549757
3. Wikipedia. Novartis. Available at http://en.wikipedia.org/wiki/Novartis