What is the recommended treatment regimen for patients taking Lisinopril (Angiotensin-Converting Enzyme inhibitor) for hypertension or heart failure?

Lisinopril Treatment Regimen for Hypertension and Heart Failure

For hypertension, start lisinopril at 10 mg once daily and titrate to 20-40 mg daily based on blood pressure response; for heart failure, start at 2.5-5 mg once daily and aggressively titrate to the target dose of 30-40 mg daily to reduce mortality and hospitalizations. 1, 2

Initial Dosing

Hypertension

• Start with 10 mg once daily in treatment-naive patients 1
• Start with 5 mg once daily if the patient is already on diuretics 1
• Titrate at intervals of at least 2 weeks based on blood pressure response 3, 4
• Usual maintenance range: 20-40 mg once daily 1, 2
• Maximum studied dose is 80 mg daily, though doses above 40 mg provide minimal additional benefit 1

Heart Failure with Reduced Ejection Fraction

• Start with 5 mg once daily when used with diuretics and digitalis 1, 2
• Start with 2.5 mg once daily if serum sodium <130 mEq/L 1, 2
• Target dose is 30-40 mg once daily - this is critical for optimal outcomes 2, 3
• The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) reduced death or hospitalization by 12% and hospitalizations by 24% compared to low doses (2.5-5 mg daily) 2, 3

Post-Myocardial Infarction

• In hemodynamically stable patients within 24 hours of MI: 1
  • 5 mg orally initially
  • 5 mg after 24 hours
  • 10 mg after 48 hours
  • Then 10 mg once daily for at least 6 weeks
• Start with 2.5 mg if systolic BP is 100-120 mmHg in the first 3 days 1, 3

Titration Strategy

The most common clinical error is failure to titrate to target doses - many clinicians stop at low doses despite clear evidence that higher doses improve outcomes 3. Follow this algorithm:

• Increase dose every 2 weeks if tolerated 3, 4
• Check blood pressure, renal function (creatinine), and potassium 1-2 weeks after each dose increase 2, 3, 4
• Recheck at 3 months, then every 6 months thereafter 2, 4
• Aim for target dose or maximum tolerated dose - do not settle for subtherapeutic dosing 3, 4

Monitoring Parameters and Acceptable Changes

Renal Function

• An increase in creatinine up to 50% above baseline, or to 3 mg/dL (whichever is greater), is acceptable and does not require discontinuation 3, 4
• Only discontinue if creatinine rises substantially beyond these thresholds 2
• Monitor more frequently in patients with baseline renal impairment 2

Potassium

• Check potassium after 5-7 days of starting therapy 2, 3
• Recheck every 5-7 days during titration until values stabilize 2, 3
• Do not use if baseline potassium ≥5.0 mEq/L 2
• Avoid potassium-sparing diuretics during initiation unless specifically needed for persistent hypokalemia 2, 3

Blood Pressure

• Monitor for hypotension, especially after first dose 2, 1
• Hypotension after initial dose does not preclude careful subsequent titration 1
• Consider starting dose in evening when patient is supine to minimize hypotensive effects 2

Dose Adjustments for Renal Impairment

• Creatinine clearance >30 mL/min: No adjustment needed 1
• Creatinine clearance 10-30 mL/min: Start with half the usual dose (5 mg for hypertension, 2.5 mg for heart failure), titrate to maximum 40 mg daily 1
• Creatinine clearance <10 mL/min or hemodialysis: Start with 2.5 mg once daily 1

Combination Therapy

With Diuretics

• Thiazide or thiazide-type diuretics should be used together with ACE inhibitors for blood pressure control and volume management 2
• If blood pressure not controlled with lisinopril alone, add low-dose hydrochlorothiazide (12.5 mg) 1
• May need to reduce diuretic dose temporarily when initiating lisinopril to minimize hypotension 2, 1

With Beta-Blockers

• Beta-blockers (carvedilol, metoprolol succinate, bisoprolol, or nebivolol) should be used in combination with ACE inhibitors for heart failure with reduced ejection fraction 2
• This combination is Class I, Level of Evidence A 2

With Aldosterone Antagonists

• Add spironolactone or eplerenone for NYHA class II-IV heart failure with EF <35-40% despite ACE inhibitor and beta-blocker 2
• Monitor potassium frequently when combining with ACE inhibitors 2
• Do not use if creatinine ≥2.5 mg/dL (men) or ≥2.0 mg/dL (women), or if potassium ≥5.0 mEq/L 2

Critical Precautions and Drug Interactions

Avoid These Medications

• NSAIDs and COX-2 inhibitors - worsen renal function and reduce ACE inhibitor efficacy 2, 3
• Potassium supplements during initiation unless specifically indicated 2, 3
• In heart failure with reduced EF, avoid: non-dihydropyridine calcium channel blockers (verapamil, diltiazem), clonidine, moxonidine, and hydralazine without nitrate 2

Managing ACE Inhibitor Cough

• Occurs in up to 20% of patients 2
• Cough rarely requires discontinuation - only switch to ARB if cough is proven ACE inhibitor-related through withdrawal and rechallenge 3
• ARBs (candesartan, valsartan, losartan) are alternatives if ACE inhibitor truly not tolerated 2

Angioedema Risk

• Occurs in <1% but is life-threatening 2
• More common in Black patients 2
• If angioedema occurs, avoid all ACE inhibitors for life 2
• Use caution when substituting ARB, as cross-reactivity can occur 2

Special Populations

Pediatric Patients (≥6 years)

• Start with 0.07 mg/kg once daily (maximum 5 mg) 1
• Titrate to maximum 0.61 mg/kg once daily (maximum 40 mg) 1
• Only use if GFR >30 mL/min/1.73m² 1

Elderly Patients

• No specific dose adjustment required, but monitor closely for hypotension and renal function 5

Blood Pressure Targets

Hypertension with Increased Cardiovascular Risk

• **Target blood pressure <130/80 mmHg** in patients with increased cardiovascular risk (age >75, established vascular disease, chronic kidney disease, or Framingham Risk Score >15%) 2

Heart Failure with Hypertension

• Titrate GDMT to achieve systolic blood pressure <130 mmHg 2
• Use evidence-based doses of medications that both treat heart failure and lower blood pressure 2