Cardiovascular Disease Management

Introduction to RAAS Inhibitors

• The Renin-Angiotensin-Aldosterone System (RAAS) plays a critical role in regulating blood pressure and fluid balance through several key steps, including renin release, angiotensinogen conversion, angiotensin I conversion, angiotensin II effects, and aldosterone effects, which lead to vasoconstriction, increased sodium reabsorption, and aldosterone secretion 1, 2
• The American Heart Association recommends ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists as primary medications for managing RAAS-related hypertension, with calcium channel blockers and diuretics often used as complementary agents 3

Heart Failure Management

• For heart failure with reduced ejection fraction (HFrEF, EF <50%), the European Society of Cardiology recommends ACE inhibitor (or ARB if ACE inhibitor not tolerated) plus beta-blocker as initial therapy 4, 5
• The European Society of Cardiology recommends considering sacubitril/valsartan instead of ACE inhibitors in HFrEF patients remaining symptomatic despite treatment with ACEIs, beta-blockers, and MRAs 5
• For heart failure with preserved ejection fraction (HFpEF, EF ≥50%), the European Society of Cardiology recommends SGLT2 inhibitors to improve outcomes, and considering ARBs and/or MRAs to reduce heart failure hospitalizations 6

Hypertension Management

• The European Society of Cardiology recommends starting with an ACE inhibitor or ARB for patients with confirmed blood pressure (BP) ≥140/90 mmHg 6
• The European Society of Cardiology recommends considering combination therapy with a renin-angiotensin-aldosterone system (RAAS) inhibitor plus a calcium channel blocker or thiazide diuretic for patients with BP ≥150/90 mmHg 6
• Initial therapy with two drugs or a single-pill combination is recommended for patients with confirmed BP ≥150/90 mmHg, according to the European Heart Journal 7

Special Populations

• The European Society of Cardiology recommends initial therapy with a diuretic or calcium channel blocker (CCB), either alone or with a RAAS inhibitor, for black patients 6
• The European Society of Cardiology recommends starting a RAAS inhibitor when office BP ≥140/90 mmHg and targeting systolic blood pressure (SBP) to 130 mmHg and <130 mmHg if tolerated, but not <120 mmHg, for diabetic patients 6
• The American College of Cardiology recommends using ACE inhibitors or ARBs as first-line options for patients with diabetes, chronic kidney disease, or high cardiovascular risk, due to their proven mortality and morbidity benefits 8

Chronic Kidney Disease (CKD) Management

• The European Society of Cardiology recommends treating diabetic or non-diabetic CKD patients with office BP ≥140/90 mmHg with lifestyle advice and RAAS inhibitors 6
• The European Society of Cardiology recommends targeting systolic BP to 130-139 mmHg for CKD patients, and to 120-129 mmHg if tolerated for moderate-to-severe CKD patients with eGFR >30 mL/min/1.73 m² 6
• The National Kidney Foundation indicates that ACE inhibitors and ARBs have shown renoprotective effects beyond blood pressure lowering 9

Resistant Hypertension Management

• The European Society of Cardiology recommends adding low-dose spironolactone (mineralocorticoid receptor antagonist, MRA) to existing treatment for resistant hypertension 6
• The European Society of Cardiology suggests that MRAs can be effective for resistant hypertension and can reduce myocardial fibrosis, particularly in patients with heart failure with reduced ejection fraction (HFrEF) 8

Potassium Management

• The European Society of Cardiology recommends monitoring potassium levels regularly, especially in patients with renal impairment or diabetes 8
• The European Society of Cardiology recommends stopping RAAS inhibitors when potassium levels are >6.0 mEq/L, and reducing the dose or stopping RAAS inhibitors when potassium levels are >5.5 mEq/L 8
• Regular monitoring of potassium levels is essential, especially when using MRAs or potassium-sparing diuretics, or in patients with renal impairment or diabetes, as emphasized by the European Society of Cardiology 8

Medication Benefits and Side Effects

Combination Therapy

• The combination of ACE inhibitors and calcium channel blockers is recommended for CV event reduction, with strong evidence supporting this combination 10
• The combination of ARB and diuretic is effective for blood pressure control, according to the European Heart Journal 10
• Dual RAAS blockade is not recommended due to increased risk of renal events and hyperkalemia, as shown in the ONTARGET and ALTITUDE trials 10
• Fixed-dose combinations in a single tablet improve medication adherence and increase BP control rates, as reported in the European Heart Journal 10