• Clinical science

Renin-angiotensin-aldosterone system inhibitors

Abstract

Renin-angiotensin-aldosterone system (RAAS) inhibitors are a group of drugs that act by inhibiting the renin-angiotensin-aldosterone system (RAAS) and include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and direct renin inhibitors. ACE inhibitors and ARBs are commonly used in the treatment of patients with hypertension, heart failure with reduced ejection fraction, certain types of chronic kidney disease, and patients who have suffered a myocardial infarction. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g. ARBs), while angioedema and hyperkalemia may occur in both ARBs and ACE inhibitor use. Direct renin inhibitors may be considered in hypertensive patients if ACE inhibitors or ARBs are not well tolerated; however, they should never be used in combination with other RAAS inhibitors.

Overview

The renin-angiotensin-aldosterone system (RAAS)

Types of RAAS inhibitors

Drug names Indications
ACE inhibitors Enalapril, lisinopril, ramipril, captopril, benazepril
ARBs

Valsartan, candesartan, losartan, irbesartan

Direct renin inhibitors Aliskiren

References:[1][2][3][4][5][6][7][7][8][9]

Effects

Mechanism of action and effect
ACE inhibitors
ARBs (sartans)
Direct renin inhibitors

References:[2][9][10]

Side effects

ACE inhibitors

ARBs

  1. Angioedema
  2. Hyperkalemia

Direct renin inhibitors

  1. Rash
  2. Diarrhea

Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with pre-existing kidney disease or in combination with NSAIDs!
References:[8][11][12]

We list the most important adverse effects. The selection is not exhaustive.

Contraindications

Contraindications for ACE inhibitors and ARBs

  • Absolute contraindications
    • Hypersensitivity
    • C1 esterase inhibitor deficiency (due to predisposition to angioedema)
    • Pregnancy
    • Breastfeeding
  • Relative contraindications

Contraindications for direct renin inhibitors

  • Hypersensitivity
  • Drug interactions (see “Interactions” below)

Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR!
References:[13][14][2][8][15][16]

We list the most important contraindications. The selection is not exhaustive.

Interactions

Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or pre-existing kidney disease!
References:[17][18][19][20][21]

Guidelines & therapy recommendations

References:[2][16]