PH4.6 | PH4.6 | Renin Angiotensin Aldosterone System Modulators — Summary & Reflection

KEY TAKEAWAYS

The RAAS cascade — renin → Ang I → ACE → Ang II → AT1 — is therapeutically targeted at four distinct points by ACEi, ARBs, ARNIs, and aliskiren. ACEi are first-line agents in HFrEF, post-MI, diabetic nephropathy, and high-risk cardiovascular prevention; their main ADRs are cough (class effect, bradykinin) and angioedema (rare but serious). ARBs lack the cough (no bradykinin accumulation) and are the appropriate substitute when ACEi-induced cough is intolerable; both classes share the same contraindications (pregnancy, bilateral renal artery stenosis, hyperkalaemia). The ARNI sacubitril/valsartan has superseded ACEi in HFrEF following PARADIGM-HF — but requires a mandatory 36-hour washout from ACEi to prevent dangerous angioedema. Aliskiren (direct renin inhibitor) is not recommended in combination with ACEi/ARBs. All RAAS modulators require creatinine and potassium monitoring at initiation and dose changes; the 'triple whammy' of ACEi/ARB + NSAID + diuretic can precipitate AKI and warrants explicit patient counselling.

REFLECT

Return to the opening case: the 58-year-old diabetic with microalbuminuria and hypertension who developed ACEi-induced cough on ramipril.

1. Using the mechanism you have now studied, explain to this patient in simple terms why the cough happened.
2. Which drug would you prescribe as an alternative? At what dose, and what monitoring would you arrange?
3. Is his eGFR of ~52 a contraindication to your chosen RAAS modulator? What creatinine rise would concern you at his 2-week review?
4. Over the next 5 years, what outcome do you expect from RAAS blockade — and what two laboratory values track that benefit?
5. If he develops heart failure in the future and his cardiologist wants to switch him to sacubitril/valsartan, what critical transitional step is required?

This patient's trajectory — from microalbuminuria to CKD prevention to HF management — illustrates why RAAS pharmacology is not a pharmacology topic but a career-long clinical skill.