Aliskiren (Rasilez▼): risk of cardiovascular and renal adverse reactions
- Medicines and Healthcare products Regulatory Agency
- 8 March 2012
- Therapeutic area:
- Cardiovascular disease and lipidology
New contraindications and warnings for combination of aliskiren (Rasilez) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
Article date: March 2012
Aliskiren inhibits the renin-angiotensin-aldosterone system (RAAS) by a direct effect on renin, blocking the conversion of angiotensinogen to angiotensin I. It has been licensed in the UK since 2007 for the treatment of essential hypertension at a dose of 150–300 mg once a day.
Early discontinuation of the ALTITUDE study
The ALTITUDE study (ALiskiren Trial In Type 2 diabetes Using cardiovascular and renal Disease Endpoints) was a 4-year, multicentre, randomised, placebo-controlled trial that looked at type II diabetic patients at high risk of cardiovascular and renal events who were randomised to receive either aliskiren 300 mg daily or placebo.
The study was designed to evaluate the effect of aliskiren on the risk of cardiovascular and renal events in these high-risk patients. All patients recruited into the trial were already taking either an ACE inhibitor or ARB, so those patients randomised to the aliskiren group received two agents that block the RAAS (dual RAAS block). In total, over 8600 patients were recruited into the study.
The ALTITUDE study was halted early in December 2011 following an interim analysis that showed:
- study patients were unlikely to benefit from aliskiren; and
- an increased incidence of non-fatal strokes, renal complications (including acute renal failure), hyperkalaemia and hypotension in patients randomised to the aliskiren group
In January 2012 prescribers were informed of the interim results of the ALTITUDE trial and advised that aliskiren in combination with an ACE inhibitor or an ARB is contraindicated in all diabetic patients.
Latest advice following a Europe-wide review
Further review of analyses from the ALTITUDE study, alongside all data from other studies and spontaneous reports of suspected adverse drug reactions now confirm a risk of adverse outcomes (hypotension, syncope, stroke, hyperkalaemia, and changes in renal function including acute renal failure) when aliskiren is combined with ACE inhibitors or ARBs, especially in diabetic patients and those with impaired renal function. Although less evidence is available for other patient groups, adverse outcomes cannot be excluded and therefore the combination is not recommended for any patient.
Severe renal impairment
In addition, prescribers should note that use of aliskiren is no longer recommended in any patient with severe renal impairment—ie, an eGFR <30 mL/min per 1.73m2, irrespective of whether it is used in combination with an ACE inhibitor or an ARB, another antihypertensive, or as monotherapy. This recommendation is based on an analysis of postmarketing surveillance data that showed an increased risk of renal adverse events and hyperkalaemia with aliskiren in this patient group.
Advice for healthcare professionals:
- prescribers should review the treatment of all patients taking aliskiren in combination with an ACE inhibitor or an ARB at a routine appointment
- in patients who are taking an ACE inhibitor or an ARB, healthcare professionals should stop aliskiren and not initiate new treatment in:
o diabetic patients; and o non-diabetic patients with an eGFR <60 mL/min per 1.73 m2
- aliskiren in combination with ACE inhibitors or ARBs is not recommended in any other patients. The benefits versus risks of continuing aliskiren treatment should be considered carefully
- If aliskiren is discontinued then alternative antihypertensive agents should be used as necessary
- use of aliskiren (either as monotherapy or in combination with other medicines) is no longer recommended in patients with severe renal impairment—ie, eGFR <30mL/min per 1.73 m2
- in all patients where aliskiren treatment is continued or initiated, eGFR and glucose tolerance should be monitored at appropriate intervals
- please report suspected adverse reactions to aliskiren on a Yellow Card (www.mhra.gov.uk/yellowcard)
Prescribers are reminded of NICE guidelines for the management of hypertension published in August 2011 and note that at present, these guidelines do not recommend the use of aliskiren.
See letter for healthcare professionals sent Feb 2012
Article citation: Drug Safety Update March 2012, vol 5 issue 9: A1.
Published: 8 March 2012
Therapeutic area: Cardiovascular disease and lipidology