What is the preferred initial treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) for a patient with hypertension (High Blood Pressure) or heart failure, considering potential contraindications such as impaired renal function or hyperkalemia?

ACE Inhibitors vs ARBs: Clinical Recommendations

ACE inhibitors should be the preferred first-line agent over ARBs for most patients with hypertension, heart failure, or post-myocardial infarction, unless the patient is intolerant to ACE inhibitors (primarily due to cough or angioedema). 1

Primary Indications Where ACE Inhibitors Are Preferred

Heart Failure with Reduced Ejection Fraction (HFrEF)

• ACE inhibitors are recommended as first-line therapy for all patients with LVEF ≤40% and for those with hypertension, diabetes, or chronic kidney disease, unless contraindicated. 1
• ACE inhibitors reduce morbidity and mortality in patients with previous or current symptoms of chronic HFrEF when ARNi (angiotensin receptor-neprilysin inhibitor) is not feasible. 1
• Beta-blockers should be added to ACE inhibitor therapy in patients with LVEF <40% and/or heart failure after stabilization. 1

Post-Myocardial Infarction

• ACE inhibitors should be started within the first 24 hours of STEMI in patients with evidence of heart failure, LV systolic dysfunction, diabetes, or anterior infarct. 1
• ACE inhibitors should be continued indefinitely in all patients who have had MI, particularly those with LVEF ≤40%. 1
• In patients with recent MI and LVEF <40%, no mortality difference has been demonstrated between ACE inhibitors and ARBs, but ACE inhibitors remain the standard of care based on extensive evidence. 2

Hypertension with Diabetes

• In patients ≥55 years with hypertension (or without hypertension but with another cardiovascular risk factor), an ACE inhibitor should be considered to reduce cardiovascular events. 1
• ACE inhibitors are preferred for BP control, primary prevention of diabetic kidney disease, and reduction of major cardiovascular and renal outcomes in type 2 diabetes. 3
• Initial drug therapy should include ACE inhibitors, beta-blockers, or diuretics as preferred agents for uncomplicated hypertension. 1

Chronic Kidney Disease with Albuminuria

• For patients with UACR ≥300 mg/g creatinine, ACE inhibitors (or ARBs) at maximum tolerated dose are recommended as first-line treatment. 1
• For patients with UACR 30-299 mg/g creatinine, ACE inhibitors or ARBs are recommended to reduce progressive kidney disease risk. 1
• ACE inhibitors may be continued as kidney function declines to eGFR <30 mL/min/1.73 m² for cardiovascular benefit without significantly increasing end-stage kidney disease risk. 1

When ARBs Are Appropriate

ACE Inhibitor Intolerance

• ARBs are recommended for patients intolerant to ACE inhibitors due to cough or angioedema who have heart failure, post-MI with LVEF ≤40%, or hypertension. 1
• Valsartan is specifically recommended as the preferred ARB alternative in patients with heart failure and/or LV systolic dysfunction who cannot tolerate ACE inhibitors. 1
• ARBs are useful in ACE-inhibitor intolerant patients with hypertension. 1

Equivalent Efficacy Scenarios

• In patients with hypertension without compelling indications, ARBs and ACE inhibitors show equivalent efficacy for blood pressure control and outcomes including all-cause mortality, cardiovascular mortality, MI, heart failure, stroke, and end-stage renal disease. 4
• For primary prevention of stroke, ACE inhibitors and ARBs demonstrate equivalent efficacy. 3

Critical Contraindications and Precautions

Absolute Contraindications

• History of angioedema with ACE inhibitors or ARBs is an absolute contraindication to that drug class. 1, 5
• Pregnancy is an absolute contraindication to both ACE inhibitors and ARBs. 5

Hemodynamic Considerations

• ACE inhibitors should not be initiated when systolic BP is <80 mmHg. 6
• Patients with systolic BP of 95 mmHg are considered high risk and require stabilization before initiating ACE inhibitors. 6
• ACE inhibitors should only be initiated when systolic BP is consistently ≥100 mmHg and the patient is euvolemic. 6

Renal Function Monitoring

• Creatinine level of 190 µmol/L (approximately 2.15 mg/dL) represents moderate renal impairment but is not an absolute contraindication. 6
• ACE inhibitors should be used with caution when creatinine is >3 mg/dL (265 µmol/L). 6, 5
• A 15-25% rise in creatinine during the first 2-4 weeks is acceptable and associated with long-term renoprotection. 6
• Discontinuation is recommended if creatinine rises >30% above baseline or potassium >5.5-5.6 mEq/L. 6
• Serum creatinine/eGFR and potassium should be monitored at least annually, and within 1-2 weeks after ACE inhibitor initiation or dose increase. 1, 6

Hyperkalemia Risk

• Risk factors include renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes. 5
• Elevated serum potassium (>5.7 mEq/L) occurs in approximately 1% of hypertensive patients and 3.8% of heart failure patients. 5

Dual Therapy: ACE Inhibitor + ARB Combination

The simultaneous use of an ACE inhibitor and ARB is potentially harmful and is not recommended for treating hypertension or any cardiovascular condition. 7

Evidence Against Combination Therapy

• The ONTARGET trial demonstrated that dual blockade increased harm without reducing cardiovascular events, despite lowering proteinuria more than single agents. 7
• Hyperkalemia risk is substantially elevated when both agents are used together. 7
• Acute kidney injury occurs more frequently with dual therapy compared to either agent alone. 7
• The American College of Cardiology provides a Class III Harm recommendation with Level A evidence against dual therapy. 7

Alternative Strategies

• If blood pressure remains uncontrolled on a single RAS blocker, add a calcium channel blocker or thiazide diuretic rather than combining ACE inhibitor with ARB. 7
• Optimize the dose of a single RAS blocker to maximum approved dose before adding other drug classes. 7

Practical Initiation Protocol for Patients with Renal Impairment

Stabilization First

• Begin with diuretic therapy alone (furosemide 20-40 mg daily) to achieve euvolemia before considering ACE inhibitors. 6
• Loop diuretics are preferred for symptomatic fluid overload, adjusting based on urine output and clinical response. 6

ACE Inhibitor Dosing

• Initial dose of lisinopril should be 2.5 mg once daily (half the usual starting dose due to renal impairment). 6
• Alternative options include enalapril 2.5 mg once daily or ramipril 1.25 mg once daily. 6

Adverse Effect Profile Comparison

ACE Inhibitor-Specific Effects

• Persistent nonproductive cough occurs with all ACE inhibitors due to bradykinin accumulation, always resolving after discontinuation. 5
• The incidence of cough tends to be overestimated, and risk can be reduced by using a lipophilic ACE inhibitor or combining with a calcium channel blocker. 3
• Angioedema risk is very low but serious; overall withdrawal rates due to adverse events are lower with ARBs than ACE inhibitors. 4

Shared Adverse Effects

• Both drug classes share serious adverse effects including hyperkalemia, renal failure, and hypotension. 2
• In one trial, angioedema was less frequent with ARB therapy (one less case per 500 patients). 2

Common Clinical Pitfalls

• Starting ACE inhibitors or beta blockers simultaneously in a hypotensive, volume-overloaded patient is a common error that must be avoided. 6
• Discontinuing ACE inhibitors for modest creatinine rises (15-30% above baseline) is not recommended, as this rise is expected and beneficial long-term. 6
• Failing to monitor renal function and potassium within 1-2 weeks after initiation or dose changes can lead to undetected complications. 6
• Using ARBs as first-line when ACE inhibitors would be more appropriate based on superior evidence for MI prevention, primary HF prevention, and secondary stroke prevention. 3