Direct renin inhibitors

Antihypertensives that block renin itself, the first step of the renin-angiotensin-aldosterone system.

Updated Nov 1, 2026

What they are

Oral drugs that inhibit renin. Aliskiren is the only one in use; it lowers blood pressure about as much as other RAAS blockers but has no outcome advantage, so it is a second-line choice.

Mechanism of action

Table 1Drugs that act on the RAAS

Drug class	Blocks	Examples	Key effects	Pregnancy
ACE inhibitors	Angiotensin-converting enzyme (ACE)	Enalapril · Captopril	Dry cough · angioedema · hyperkalaemia	Contraindicated
ARBs	Angiotensin II AT1 receptor	Losartan · Valsartan	Hyperkalaemia · cough is rare	Contraindicated
Renin inhibitor	Renin (first step of the axis)	Aliskiren	Diarrhoea · hyperkalaemia	Contraindicated
ARNI	AT1 receptor and neprilysin	Sacubitril/valsartan	Hypotension · angioedema · never with an ACE inhibitor	Contraindicated
Mineralocorticoid antagonist	Aldosterone receptor	Spironolactone · Eplerenone · Finerenone	Hyperkalaemia · gynecomastia (spironolactone)	Limited data; spironolactone is usually avoided

Five classes slow the same axis at different points, and all share the risk of hyperkalaemia.Source: Durgical, CC BY 4.0Table comparing five classes that act on the renin-angiotensin-aldosterone system: what each blocks, examples, key effects and pregnancy risk level. ACE inhibitors, ARBs, renin inhibitors and ARNIs are contraindicated in pregnancy; mineralocorticoid antagonists have limited data.

Renin cuts angiotensinogen into angiotensin I. Aliskiren occupies the active site of renin, so angiotensin I, angiotensin II and aldosterone all fall. Plasma renin concentration rises because feedback is lost, but its activity stays blocked.

Target: Renin (active site)

Drugs in this class

AliskirenThe only direct renin inhibitor: lowers blood pressure by blocking the first step of the renin-angiotensin system. A…Renin

Test yourself

Think of the answer, then tap the question to see it.

What does aliskiren do to plasma renin activity and plasma renin concentration?

Renin activity falls because the enzyme is blocked, while renin concentration rises because angiotensin II no longer feeds back.

In which patients is aliskiren contraindicated together with an ACE inhibitor or ARB?

In patients with diabetes, because of kidney injury, hyperkalaemia and hypotension.

Why is aliskiren stopped when pregnancy is detected?

Drugs acting on the renin-angiotensin system injure the developing fetus, especially in the second and third trimesters.

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