What is the recommended treatment for patients with Renin-Angiotensin-Aldosterone System (RAAS) implicated conditions, such as hypertension or heart failure?

RAAS Inhibitors in Hypertension and Heart Failure Management

Renin-Angiotensin-Aldosterone System (RAAS) inhibitors, particularly ACE inhibitors and ARBs, are the recommended first-line treatments for patients with hypertension, heart failure, diabetic nephropathy, and post-myocardial infarction, due to their proven mortality and morbidity benefits beyond blood pressure control. 1

Types of RAAS Inhibitors and Their Indications

ACE Inhibitors

• Mechanism: Block conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion 2
• Primary indications:
  • Heart failure with reduced ejection fraction (HFrEF) 3
  • Post-myocardial infarction 3
  • Diabetic nephropathy 3
  • Hypertension with high cardiovascular risk 3

Angiotensin Receptor Blockers (ARBs)

• Recommended for patients who:
  • Have indications for but are intolerant of ACE inhibitors (e.g., cough)
  • Have heart failure
  • Have had MI with LVEF ≤40% 3

Mineralocorticoid Receptor Antagonists (MRAs)

• Recommended for:
  • Post-MI patients without significant renal dysfunction or hyperkalemia who are already on ACE inhibitor and beta-blocker therapy
  • Patients with LVEF ≤40% who have either diabetes or heart failure 3
  • Resistant hypertension 3

Treatment Algorithms by Condition

Hypertension Management

1. Initial therapy:

   • For patients with confirmed BP ≥140/90 mmHg: Start with ACE inhibitor or ARB 3
   • For patients with BP ≥150/90 mmHg: Consider combination therapy with RAAS inhibitor plus calcium channel blocker or thiazide diuretic 3

2. Special populations:

   • Black patients: Initial therapy should include a diuretic or CCB, either alone or with a RAAS inhibitor 3
   • Diabetic patients: Start RAAS inhibitor when office BP ≥140/90 mmHg; target SBP to 130 mmHg and <130 mmHg if tolerated, but not <120 mmHg 3

3. Resistant hypertension:

   • Add low-dose spironolactone (MRA) to existing treatment
   • If intolerant to spironolactone, add eplerenone, amiloride, higher dose thiazide/thiazide-like diuretic, or loop diuretic 3

Heart Failure Management

1. Heart failure with reduced ejection fraction (HFrEF):

   • First-line: ACE inhibitor (or ARB if ACE inhibitor not tolerated) plus beta-blocker 3
   • Add MRA for persistent symptoms
   • Consider sacubitril/valsartan instead of ACE inhibitors in HFrEF patients remaining symptomatic despite treatment with ACEIs, beta-blockers, and MRAs 3

2. Heart failure with preserved ejection fraction (HFpEF):

   • SGLT2 inhibitors are recommended to improve outcomes 3
   • ARBs and/or MRAs may be considered to reduce heart failure hospitalizations 3

Chronic Kidney Disease Management

• For diabetic or non-diabetic CKD with office BP ≥140/90 mmHg: Treat with lifestyle advice and RAAS inhibitors 3
• Target systolic BP to 130-139 mmHg 3
• For moderate-to-severe CKD with eGFR >30 mL/min/1.73 m²: Target systolic BP to 120-129 mmHg if tolerated 3

Monitoring and Managing Side Effects

Hyperkalemia Management

• Monitor potassium levels regularly, especially in patients with renal impairment or diabetes 3

• Potassium management based on levels:

  • 6.0 mEq/L: Stop RAAS inhibitors 3

  • 5.5 mEq/L: Reduce dose or stop RAAS inhibitors 3

  • 5.1-5.5 mEq/L: Take measures to lower potassium when initiating RAAS inhibitors 3

  • 5.0 mEq/L: Do not start RAAS inhibitors; reduce dose or stop if already on therapy 3

• For patients with chronic or recurrent hyperkalemia on RAAS therapy:

  • Consider potassium-lowering agents when K+ levels are confirmed >5.0 mEq/L 3
  • Modern agents like patiromer and zirconium cyclosilicate can help maintain patients on RAAS inhibitors despite hyperkalemia risk 4

Renal Function Monitoring

• Assess renal function before starting therapy and periodically thereafter
• Use reduced initial doses in patients with creatinine clearance ≤30 mL/min 1
• Temporary discontinuation may be necessary during acute illness that may compromise renal function

Important Cautions and Contraindications

1. Avoid dual RAAS blockade:

   • Combination of ACE inhibitor and ARB is not recommended due to increased risk of renal events and hyperkalemia 5, 6
   • ONTARGET study showed ACEI/ARB combination was associated with more adverse effects without increased benefit 5

2. Pregnancy:

   • RAAS inhibitors are contraindicated during pregnancy due to risk of fetal harm

3. Volume depletion:

   • Use with caution in volume-depleted patients due to risk of hypotension 2
   • Consider lower starting doses in such patients

4. Renal artery stenosis:

   • Use with caution due to risk of acute kidney injury

By following these evidence-based recommendations and monitoring protocols, RAAS inhibitors can effectively manage hypertension, heart failure, and related conditions while minimizing adverse effects and improving patient outcomes.