New Data on Risks when Renin Inhibitor Aliskiren is Used With ARBs, ACE Inhibitors

New Data on Risks when Renin Inhibitor Aliskiren is Used With ARBs, ACE Inhibitors
The US Food and Drug Administration (FDA) is warning of possible risks when using blood pressure medicines containing aliskiren with angiotensin converting enzyme(ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with diabetes or renal impairment.

These drug combinations should not be used in patients with diabetes. In addition, a new warning is being added to avoid use of these drug combinations in patients with renal impairment.

The labels for aliskiren-containing drugs are being updated based on preliminary data from the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) study. In ALTITUDE, the risks of renal impairment, hypotension, and hyperkalaemia in a group of patients taking aliskiren plus an ARB or ACE inhibitor increased relative to a group of patients taking an ARB or ACE plus placebo.

The preliminary data from ALTITUDE also demonstrated a slight excess of cardiovascular events (death or stroke) in the aliskiren group. However, the FDA has reached no definite conclusion regarding an actual link between these drugs and death or stroke.

The FDA will evaluate the final trial results as well as results from other aliskiren trials and will communicate any new information when it becomes available.

The following recommendations are being added to the drug labels for aliskiren-containing products as of 4/20/12:
• A new contraindication against the use of aliskiren with ARBs or ACE inhibitors in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalaemia.
• A warning to avoid use of aliskiren with ARBs or ACE inhibitors in patients with moderate to severe renal impairment (ie, glomerular filtration rate <60 mL/min).

Aliskiren and valsartan (Valturna) should not be used in patients with diabetes. This drug will no longer be marketed after July 2012.

The purpose of ALTITUDE was to determine whether aliskiren plus conventional treatment reduces death and disease caused by the heart, the circulatory system, and the kidney. Patients with type 2 diabetes with renal disease were randomised to aliskiren 300 mg daily (n = 4,283) or placebo (n = 4,296). All patients were receiving concomitant therapy with an ARB or an ACE inhibitor.

The primary efficacy outcome was the time to the first event of the primary composite endpoint, which consisted of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalisation for heart failure, onset of end-stage renal disease, renal death, and doubling of serum creatinine concentration from baseline sustained for at least 1 month.

After a median patient follow up of about 27 months, the trial was terminated early for lack of efficacy. Greater risks of renal impairment, hypotension and hyperkalaemia were observed in the aliskiren group compared with the placebo group.

SOURCE: US Food and Drug Administration