Pharmacology of major drug classes used - renin-angiotensin-aldosterone inhibitors

Overview

ACE inhibitors, ARBs, and MRAs (mineralocorticoid receptor antagonists) block the RAAS at sequential points - foundational therapy across hypertension, heart failure, and CKD

Among the most extensively evidence-based cardiovascular drug classes, with mortality benefit demonstrated across multiple conditions, not just BP-lowering

Drug	Site of action	Distinguishing feature
ACE inhibitors	Block conversion of angiotensin I to II	Cough (bradykinin accumulation) - the classic distinguishing side effect vs ARBs
ARBs	Block the AT1 receptor directly	No cough (bradykinin pathway unaffected) - used when ACEi not tolerated
MRAs (spironolactone, eplerenone)	Block the aldosterone receptor	Mortality benefit in HFrEF independent of diuretic effect; risk of hyperkalaemia and (spironolactone) gynaecomastia

Never combine ACEi + ARB - no added benefit, substantially increased risk of hyperkalaemia and AKI (ONTARGET trial)
Expect and tolerate an initial eGFR fall (up to ~30%) and mild hyperkalaemia after starting/uptitrating - stop only if the rise is progressive or K+ becomes significantly elevated, not for an isolated acceptable initial change
Contraindicated in pregnancy (teratogenic) and in bilateral renal artery stenosis (precipitates AKI by removing angiotensin II-dependent efferent arteriolar tone)
Foundational to HFrEF therapy (ACEi/ARB or ARNI + MRA as two of the four pillars), and first-line for hypertension with diabetic nephropathy/proteinuric CKD given renoprotective effect independent of BP lowering

Hypertension, heart failure with reduced ejection fraction, diabetic nephropathy, primary hyperaldosteronism (MRA as treatment)

The evidence base for this class has progressively expanded from pure BP control to genuine disease-modifying therapy across heart failure and CKD

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