UKidney Nephrology News and Insights

No benefit of Aliskiren added on to ACE or ARB: a disappointing development

Plasma Renin ActivityIn a stunning development, Novartis said Tuesday that it will terminate the late-stage ALTITUDE study investigating Rasilez (aliskiren) in patients with type 2 diabetes and renal impairment on the recommendation of an independent data monitoring committee. The company indicated that the committee concluded that "patients were unlikely to benefit" from the addition of Rasilez to standard anti-hypertensives and also identified higher adverse events in this group (source: FirstWord).

On a personal and professional note, these results come as a great disappointment to me. Not only does it suggest no further protection for our patients prescribed this strategy in an effort to reduce the burden of cardiorenal disease, but I was a great believer in the hypothesis and taught about it extensively throughout my career.

Cracks began to appear in the theory of aggressive renin-angiotensin inhibition with the ONTARGET, ACCOMPLISH, ASCEND and ROADMAP studies, where patients experienced no outcome benefit despite aggressive renin-angiotension and successful lowering of urinary albumin excretion. The ALTITUDE study will call in to question, not only the role of renin inhibition, but  the rationale for albuminuria reduction as well when attempted to reduce cardiovascular end-points.

As a cautionary note, we must await the publication of this study to fully understand the findings. Furthermore, Aliskiren has been shown to be a very safe antihypertensive following over 200,00 patient-years of data. But the combination of multiple (even) safe drugs in this class, like we saw in ONTARGET with ACEi and ARBs, is not a promising strategy any longer.

Finally, a tantalizing issue lingers in the story of renin inhibition; it is conceivable that direct renin inhibition is the best way to block this system, better than ACEi and ARBs, since the latter 2 cause reflexive increase in plasma renin activity whereas aliskiren does not. However, because aliskiren was introduced so late and no head-to-head or non-inferiorty studies were ever done against ACEi or ARBs, we will likely never know.

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