Pharmacology  ·  Cardiovascular

RAAS Blockers in Heart Failure

ACE inhibitors, angiotensin receptor blockers, sacubitril/valsartan, and shared contraindications

• Renin-angiotensin-aldosterone system blockade was the first strategy shown to improve survival in heart failure; ACE inhibitors reduce angiotensin II and raise bradykinin, producing vasodilation, reduced aldosterone secretion, and anti-fibrotic effects — but the bradykinin elevation also causes the characteristic dry cough and, rarely, angioedema.
• Angiotensin receptor blockers act one step downstream, blocking the angiotensin II receptor rather than preventing its formation; because they do not raise bradykinin they eliminate the cough and substantially reduce angioedema risk, making them the alternative when ACE inhibitors are not tolerated.
• Sacubitril/valsartan is the preferred RAAS blocker in heart failure with reduced ejection fraction — sacubitril inhibits neprilysin to amplify protective natriuretic peptides, while valsartan simultaneously blocks the angiotensin II receptor to prevent the unopposed rise in angiotensin II that neprilysin inhibition alone would cause.
• All three classes share the same major contraindications: pregnancy, bilateral renal artery stenosis, and hyperkalemia risk; sacubitril/valsartan is additionally contraindicated with prior ACE inhibitor angioedema, and must never be combined with an ACE inhibitor or another ARB.
• When RAAS blockade cannot be used, the combination of hydralazine and isosorbide dinitrate provides an alternative through direct vasodilation, with particular mortality benefit demonstrated in self-identified Black patients with heart failure with reduced ejection fraction.