Renin inhibitors in hypertension

Aliskiren is the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension, and blocks the renin system at its point of activation by directly inhibiting plasma renin activity.

Side effects:

• risk of angioedema and renal dysfunction
  • The MHRA have (1)
    • warned that angioedema may occur with use of aliskiren (Rasilez®)
    • also warned that extreme caution is required if aliskiren is used in patients with renal artery stenosis or conditions predisposing to kidney dysfunction (such as hypovolaemia, heart disease, liver disease, or kidney disease) because of a risk of acute renal failure
    • NSAIDs may reduce the antihypertensive effect of aliskiren, and elderly patients or patients with compromised renal function may be at risk of further deterioration of renal function if NSAIDs and aliskiren are used together
      
      
  • more recent guidance from MRHA hasstated that (2)
    • aliskirin should not be initiated for new patients who have diabetes or an eGFR <60 mL/min/1.73 m2 if they are already are taking an ACE inhibitor or an ARB. If existing patients of this type are already taking aliskirin with either an ACE inhibitor or an ARB, the aliskirin should be stopped
    • 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, i.e. eGFR <30mL/min/1.73 m2. In all patients where aliskiren treatment is continued or initiated, eGFR and glucose tolerance should be monitored at appropriate intervals
    • report suspected adverse reactions to aliskiren on a Yellow Card
      
      
  • a MeReC review has stated that
    • "..the combination of aliskiren with ACE inhibitors or angiotensin receptor blockers (ARBs) is now contraindicated in patients with diabetes (type I or type II) and other patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. In all other patient groups, aliskiren in combination with an ACE inhibitor or an ARB is not recommended. Aliskiren (either as monotherapy or in combination with other medicines) is no longer recommended for any patient with severe renal impairment (eGFR <30 mL/min/1.73 m2).." (3)
      

Reference:

1. MeReC Monthly No.16 July 2000
2. MHRA. Aliskiren (Rasilez): risk of cardiovascular and renal adverse reactions - new contraindications and warnings. Drug Safety Update. March 2012
3. MeRec Monthly No. 48 March 2012