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Renin-angiotensin-aldosterone system inhibitors

Last updated: February 1, 2021

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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 inhibitors (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, and certain types of chronic kidney disease, as well as patients who have had 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 with 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.

The renin-angiotensin-aldosterone system (RAAS)

Types of RAAS inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhibitors)

Angiotensin-receptor blocker (ARBs, sartans)

  • Drug names: valsartan, candesartan, losartan, irbesartan
  • Indications: same as ACE inhibitors, mostly used as second-line treatment if ACE inhibitors are not tolerated
    • Angioedema: can be tried under close surveillance if no adequate alternative is available [5]
    • Non-life-threatening side effects (e.g., dry cough; ): commonly used

Direct renin inhibitors

ACE inhibitors

ARBs

Direct renin inhibitors

aLESkiREN: LESS RENin with aliskiren.

ACE inhibitors

Side effects of CAPTOPRIL: Cough, Angioedema, Pemphigus vulgaris, Teratogenicity, hypOtension, high Potassium, Renal failure, Increased creatinine, Low GFR.

ARBs

Direct renin inhibitors

Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with preexisting kidney disease or in combination with NSAIDs

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

Contraindications for ACE inhibitors and ARBs

Normally, angiotensin II constricts efferent vessels, increasing the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, reducing the GFR.

Contraindications for direct renin inhibitors

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

ACE inhibitors and ARBs [12]

Direct renin inhibitors [15]

Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or preexisting kidney disease.

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