Drugs that act on the renin-angiotensin system (RAS) include:
- angiotensin-receptor blockers (ARBs)
- angiotensin-coverting enzyme inhibitors (ACE inhibitors) and
- direct renin inhibitors (aliskiren).
Following an EU review (including data from the ONTARGET, ALTITUDE and VA NEPHRON-D studies and a meta-analysis by Makani), healthcare professionals are advised not to prescribe an ACE inhibitor in combination with an ARB in patients with diabetic nephropathy as these individuals are already at risk of developing hyperkalaemia.
Candesartan and valsartan are licensed as add-on therapy to ACE inhibitors for people with symptomatic heart failure who require such a combination despite optimal therapy. Combination therapy should be limited to patients intolerant of mineralocorticoid antagonists and with persistent symptoms despite other optimal therapy. The triple combination of an ACE inhibitor, ARB, and a mineralocorticoid receptor antagonist or other potassium-sparing diuretic is not recommended.
Aliskiren in combination with an ACE inhibitor or ARB is contraindicated in patients with renal impairment (eGFR <60ml/min/1.73m2) or diabetes.
Patients currently on combination treatment
Individuals currently receiving combination therapy with RAS-blocking agents should be reassessed at their next routine appointment to determine the need for ongoing treatment.
If combination treatment is necessary, it must be carried out under specialist supervision with blood pressure, renal function and electrolytes monitored at the start of therapy and monthly thereafter, as well as after any dose change and during intercurrent illness.