Lisinopril. What diseases does it treat?

Use lisinopril to lower blood pressure, treat heart failure with reduced ejection fraction, reduce mortality and remodeling after myocardial infarction, and slow progression of diabetic nephropathy. For uncomplicated hypertension, typical initiation is 10 mg once daily, titrating to 20–40 mg once daily as needed; the maximum recommended dose is 80 mg/day. Adjust initiation dose to 2.5–5 mg for older adults or patients with renal impairment and uptitrate gradually while monitoring vital signs and labs.

For heart failure with reduced ejection fraction, initiate at 2.5–5 mg once daily and increase every 1–2 weeks as tolerated toward target doses commonly used in trials (20–40 mg/day). After acute myocardial infarction, start when hemodynamically stable (examples: initial 5 mg then titrate) to reduce remodeling and long-term mortality. For diabetic nephropathy, aim for doses that control blood pressure (frequently 10–40 mg/day) to reduce albuminuria; combine with glycemic and lipid control for best renal outcomes.

Before initiating lisinopril, obtain baseline serum creatinine and potassium; recheck within 1–2 weeks after starting or changing dose, and again periodically thereafter. Expect a modest rise in creatinine; increases up to 30% from baseline can be acceptable, while greater rises require reassessment for bilateral renal artery stenosis or volume depletion. Monitor blood pressure within days of initiation and watch for serum potassium > 5.5 mEq/L which requires prompt management. Avoid concurrent use of potassium supplements, potassium-sparing diuretics, or NSAIDs without careful monitoring; combine cautiously with ARBs or direct renin inhibitors.

Do not use lisinopril during pregnancy because it poses fetal risk; switch pregnant patients to alternative antihypertensives such as labetalol or nifedipine. Stop ACE inhibitors and seek urgent care for angioedema (facial or oropharyngeal swelling). Expect common adverse effects such as persistent dry cough, hypotension, hyperkalemia, and possible renal function decline; reduce or hold diuretics before initiation in volume-depleted patients to lower the risk of symptomatic hypotension. Communicate clearly with patients about when to report dizziness, oliguria, progressive leg swelling, or signs of allergic reaction, and schedule lab checks as part of routine follow-up.

Mechanism of Action: How Lisinopril Lowers Blood Pressure and Onset of Response

Start lisinopril at 10 mg once daily for most adults with normal renal function; reduce the initial dose to 2.5–5 mg for patients who are volume-depleted, are taking diuretics, or have renal impairment.

Lisinopril inhibits angiotensin-converting enzyme (ACE), which lowers circulating angiotensin II levels. Reduced angiotensin II causes arteriolar dilation (decreasing systemic vascular resistance/afterload) and efferent glomerular arteriole dilation (reducing intraglomerular pressure). Lower angiotensin II also decreases aldosterone secretion, promoting natriuresis and a fall in plasma volume that reduces preload.

ACE inhibition raises bradykinin concentrations by blocking its breakdown. Increased bradykinin contributes to additional vasodilation and to adverse effects–persistent dry cough typically appears weeks to months after starting therapy, and angioedema can occur at any time.

Pharmacokinetics explain the clinical time course: oral bioavailability ~25%, time to peak concentration (Tmax) 6–8 hours, and terminal half-life about 12 hours in patients with normal renal function. Expect measurable BP reduction within 1 hour of the first dose, maximal antihypertensive effect at ~6–8 hours, and stabilization of the full antihypertensive response over 2–4 weeks with continued dosing. Because the drug is excreted unchanged by the kidneys, half-life and exposure increase as renal function falls.

Adverse hemodynamic and laboratory changes follow characteristic timing. First-dose symptomatic hypotension can develop within hours in sodium-depleted or diuretic-treated patients. Serum creatinine and potassium commonly change within the first 1–2 weeks; plan biochemical recheck in that window after initiation or dose escalation. Cough often arises after weeks; angioedema onset is unpredictable. Expect hyperkalemia risk early after starting if the patient uses potassium supplements, potassium-sparing diuretics, or has baseline renal dysfunction.

Apply practical measures: check BP and electrolytes (serum creatinine and K+) within 1–2 weeks of starting or increasing a dose, reduce starting dose and extend titration intervals in renal impairment or advanced age, avoid concurrent potassium supplements or potassium-sparing diuretics unless monitored, and withhold or adjust dose in patients with bilateral renal artery stenosis or prior angioedema from an ACE inhibitor.

Hypertension Dosing Strategy: Starting Dose, Titration Steps, and Target Blood Pressure

Start most adults on lisinopril 10 mg once daily; increase to 20–40 mg once daily as the usual maintenance range and do not exceed 80 mg/day unless a specialist directs otherwise.

Initiate at 2.5–5 mg once daily for patients who are volume-depleted, taking a diuretic, elderly, or have significant renal impairment; consider holding or reducing diuretic dose prior to starting lisinopril to reduce the risk of symptomatic hypotension.

Titrate in 2–4 week intervals based on blood pressure response and tolerability: common stepwise regimens include 5 → 10 → 20 → 40 mg or 10 → 20 → 40 → 80 mg. If BP falls adequately at any step, maintain that dose rather than escalating further.

Target blood pressure: aim for <130/80 mmHg for most adults with hypertension. For patients aged ≥65 years who tolerate treatment well, target systolic <130 mmHg; select a higher target (for example <140/90 mmHg) for frail elderly or those with recurrent orthostatic symptoms. Set individualized goals for patients with diabetes, CKD, or cardiovascular disease, commonly aligning with <130/80 mmHg when tolerated.

Monitor serum creatinine and potassium at baseline and again 1–2 weeks after initiation or dose increase; if creatinine rises >30% from baseline or potassium >5.5 mmol/L, reduce dose or stop therapy and reassess. Check blood pressure within 1–2 weeks of a dose change and more frequently if symptoms of hypotension appear.

If blood pressure remains above target at maximally tolerated lisinopril dose, add a complementary antihypertensive (thiazide-type diuretic or calcium-channel blocker) rather than exceeding recommended lisinopril limits. Discontinue lisinopril immediately for angioedema or pregnancy and arrange alternative therapy.

Post‑Myocardial Infarction Use: When to Initiate Lisinopril and Short‑Term Goals

Start lisinopril within 24 hours for hemodynamically stable patients who have left ventricular systolic dysfunction (EF ≤40%), clinical heart failure after myocardial infarction, or large anterior infarct; delay initiation if the patient requires vasopressor support or has cardiogenic shock.

Initiation protocol

• Baseline tests: measure serum creatinine and potassium before first dose and document blood pressure and heart rate.
• Usual starting dose: 5 mg PO once daily for most adults. Use 2.5 mg once daily for age ≥75, low body weight, SBP <110 mmHg, or significant renal impairment (eGFR <30 mL/min/1.73 m2).
• Early uptitration: if SBP remains ≥100 mmHg and creatinine/K stable at 24–48 hours, increase to 10 mg once daily. Consider outpatient titration to maintenance dose (commonly 10–20 mg daily, up to 40 mg) over 1–4 weeks based on tolerance.
• Do not start or continue if history of angioedema, bilateral renal artery stenosis, pregnancy, or serum potassium >5.5 mEq/L; consult nephrology if renal artery stenosis suspected.

Monitoring and short‑term clinical goals

• Hemodynamics: maintain systolic BP ≥100 mmHg and avoid a drop >20 mmHg from baseline. Adjust dose or hold lisinopril for symptomatic hypotension.
• Renal function and potassium: recheck creatinine and K at 24–72 hours after initiation or dose change, then again at 1–2 weeks. Expect an early creatinine rise up to 30%; if creatinine increases >30% or K rises >5.5 mEq/L, reduce dose or stop and reassess causes.
• Clinical targets in first 30 days: limit adverse left ventricular remodeling, reduce pulmonary congestion, and lower risk of early heart failure progression. Track symptoms (dyspnea, orthopnea), daily weight, and signs of volume overload.
• Medication reconciliation: continue or start concurrently with beta‑blockers and high‑intensity statin unless contraindicated. Avoid combining with an ARB or aliskiren in patients with renal dysfunction or hyperkalemia risk.
• Discharge plan: document starting dose, stepwise uptitration plan, lab monitoring schedule, and who will check creatinine/K within 3–7 days after discharge.

Heart Failure (HFrEF) Indications: When to Start, Dose Up‑Titration, and Monitoring

Start lisinopril in patients with LVEF ≤40% who are hemodynamically stable and not contraindicated; initiate 2.5–5 mg once daily and uptitrate every 1–2 weeks as tolerated toward a target of 20–40 mg once daily (or 10–20 mg twice daily depending on local practice).

Begin therapy when the patient is euvolemic or after diuretic dose adjustment to avoid excessive hypotension. Use 2.5 mg for patients who are elderly, volume‑depleted, on multiple antihypertensives, or have baseline systolic blood pressure <100 mmHg. For moderate-to-severe renal impairment (eGFR <30 mL/min/1.73 m2) start 2.5 mg and increase more slowly with close monitoring.

Titrate by doubling the dose every 1–2 weeks: 2.5 → 5 → 10 → 20 → 40 mg daily, stopping escalation if symptomatic hypotension, a marked rise in creatinine, or hyperkalemia occurs. If intolerance develops at higher doses, maintain the highest tolerated dose rather than discontinuing ACE inhibitor therapy without alternatives.

Monitor serum creatinine/eGFR and potassium at baseline, within 1–2 weeks after initiation or any dose increase, and again at 4–6 weeks; thereafter check every 3 months or more frequently if renal function or potassium is unstable. Measure blood pressure at each visit and ask patients to report dizziness or syncope.

Use these action thresholds: hold or reduce dose if systolic BP <90 mmHg with symptoms; recheck renal function if serum creatinine rises >30% from baseline – if rise ≤30% continue and recheck in 1 week, if >30% stop and investigate; hold lisinopril and treat if K+ ≥5.5 mEq/L, recheck within 24–48 hours and manage hyperkalemia per protocol.

Address common management issues: reduce diuretic dose or correct volume depletion before stopping lisinopril if hypotension occurs; avoid initiating potassium supplements or high‑dose potassium‑sparing diuretics without close monitoring; counsel patients to stop NSAIDs when possible and to notify for pregnancy or angioedema signs (facial/lip/tongue swelling or airway compromise).

Do not rechallenge after angioedema. If ACE inhibitor intolerance persists, consider ARNI or ARB per guideline pathways once contraindications are excluded and after specialist input for complex cases.

Item	Recommendation
Indication	LVEF ≤40% (symptomatic or asymptomatic with reduced EF) unless contraindicated
Initial dose	2.5–5 mg PO once daily (use 2.5 mg for elderly, volume depletion, low BP, or renal impairment)
Titration schedule	Double dose every 1–2 weeks (2.5 → 5 → 10 → 20 → 40 mg) as tolerated
Target dose	20–40 mg daily (or equivalent split dosing); reach highest tolerated dose
Monitoring timeline	Baseline labs; recheck 1–2 weeks after start or dose change; at 4–6 weeks; then every ~3 months or as needed
Action thresholds	Hold or reduce if symptomatic SBP <90 mmHg; stop if creatinine rises >30%; hold if K+ ≥5.5 mEq/L
Contraindications / immediate stop	Pregnancy, history of ACE‑inhibitor–related angioedema, bilateral renal artery stenosis

Diabetic Nephropathy Management: Using Lisinopril to Reduce Proteinuria and Track Kidney Function

Use lisinopril to reduce albuminuria and slow renal function decline in patients with albuminuric diabetic nephropathy, unless contraindications (history of angioedema, pregnancy, bilateral renal artery stenosis) are present.

Dosing guidance: for most adults begin with 5–10 mg once daily and titrate toward a maintenance range of 10–40 mg once daily as tolerated. In patients with eGFR <30 mL/min/1.73 m2 use lower initial doses (2.5–5 mg) and smaller titration steps; maximum daily dose commonly remains 40 mg but adjust based on response and tolerability.

Baseline assessment: measure serum creatinine and potassium, calculate eGFR, obtain a spot urine albumin-to-creatinine ratio (ACR) or 24-hour urine protein, and record blood pressure. Repeat serum creatinine and potassium 7–14 days after initiation or after each dose increase, then at 4–6 weeks; if stable, monitor every 3 months during the first year and every 6 months thereafter.

Acceptable laboratory changes: an increase in serum creatinine up to 30% from baseline after starting or increasing lisinopril is often acceptable and can reflect hemodynamic effect. If creatinine rises >30% or absolute rise >0.5 mg/dL, reassess for reversible causes (volume depletion, NSAIDs, renally active agents), reduce dose or stop lisinopril, and consider nephrology referral.

Proteinuria targets and timing: expect a measurable reduction in ACR within 4–12 weeks; many patients achieve a 30–50% fall in albuminuria. Recheck ACR at 3 months after reaching a stable lisinopril dose and then every 3–6 months. Aim for ACR <30 mg/g if achievable; a sustained reduction of >30% from baseline correlates with better renal outcomes.

Hyperkalemia management: check potassium at baseline, 7–14 days after dose changes, and periodically thereafter. If K rises to 5.5–6.0 mmol/L, reassess diet and interacting drugs (potassium supplements, potassium-sparing diuretics, trimethoprim, NSAIDs); consider dose reduction. If K >6.0 mmol/L, stop lisinopril and manage hyperkalemia urgently.

Drug interactions and co-therapy: avoid concomitant NSAIDs and high-dose diuretics during initiation. Combining an ACE inhibitor with an ARB or direct renin inhibitor for the sole purpose of reducing proteinuria is not recommended because of higher risks of renal dysfunction and hyperkalemia. Use thiazide or loop diuretics, calcium-channel blockers, or mineralocorticoid antagonists as indicated for blood pressure and proteinuria control with careful monitoring.

When to involve nephrology: refer if eGFR falls rapidly (>25% decline or sustained decline to <30 mL/min/1.73 m2), creatinine increases >30% despite reversible causes addressed, persistent ACR >300 mg/g despite optimized therapy, recurrent hyperkalemia limiting ACE inhibitor use, or diagnostic uncertainty about the renal lesion.

Contraindications and Safety Flags: Pregnancy, Angioedema History, Renal Artery Stenosis, and Hyperkalemia Guidance

Do not prescribe lisinopril to pregnant patients; discontinue immediately if pregnancy is confirmed and arrange obstetric follow‑up.

Pregnancy and women of childbearing potential

Exposure to lisinopril in the second or third trimester causes fetal renal dysplasia, oligohydramnios, pulmonary hypoplasia and neonatal renal failure; stop the drug as soon as pregnancy is known. For women of reproductive potential, verify reliable contraception and discuss switching to safer alternatives prior to conception (typical alternatives: labetalol, nifedipine ER, or methyldopa). If first‑trimester exposure has occurred, arrange targeted fetal ultrasound and specialist obstetric consultation to assess anatomy and growth.

Angioedema, renal artery stenosis and immediate actions

Do not give lisinopril to anyone with prior ACE inhibitor–related angioedema or to patients with hereditary or idiopathic angioedema. If angioedema develops on therapy (facial/tongue/laryngeal swelling or respiratory compromise), stop lisinopril immediately, secure the airway, treat acutely (epinephrine and supportive measures as indicated) and refer to ENT/allergy for definitive evaluation. Do not rechallenge with any ACE inhibitor; avoid ARBs unless an allergy specialist has assessed the risk and a clear plan is in place.

Avoid initiation in patients with bilateral renal artery stenosis or stenosis of a solitary functioning kidney because of high risk of acute renal failure. If unexplained acute rise in serum creatinine follows initiation or dose escalation, stop lisinopril and evaluate for renovascular disease with appropriate imaging (renal duplex, CT or MR angiography) and vascular/nephrology referral.

Baseline and early monitoring: obtain serum creatinine (or eGFR) and serum potassium prior to starting lisinopril. Repeat both tests within 3–7 days and again at 2 weeks after initiation or after any dose increase; adjust frequency for renal impairment or concomitant interacting drugs.

Action thresholds for creatinine: if creatinine increases by ≤30% from baseline and the patient is clinically stable, continue therapy with close monitoring. If creatinine rises >30% or by an absolute increase >44 µmol/L (≈0.5 mg/dL), stop lisinopril, investigate for renal artery stenosis or other causes, and consult nephrology.

Hyperkalemia surveillance and management: check serum potassium before starting lisinopril. Avoid starting if K+ >5.5 mmol/L. Recheck K+ within 3–7 days and at 2 weeks; thereafter, monitor every 3 months for the first year and then every 6–12 months if stable, with more frequent checks for CKD or co‑medications that raise potassium.

Manage elevated potassium as follows: for K+ ≥6.0 mmol/L, stop lisinopril and treat as emergency hyperkalemia. For K+ 5.5–5.9 mmol/L, stop or reduce dose, remove reversible contributors (potassium supplements, salt substitutes, NSAIDs, trimethoprim, heparin, MRAs, potassium‑sparing diuretics), institute dietary potassium restriction, and consider a loop or thiazide diuretic if volume and renal function permit. For persistent chronic hyperkalemia, consider long‑term potassium binders (patiromer or sodium zirconium cyclosilicate) in collaboration with nephrology.

Drug interaction checklist: before prescribing, review concomitant medications that increase hyperkalemia or renal injury risk (spironolactone/eplerenone, amiloride/triamterene, ARBs, NSAIDs including COX‑2 inhibitors, trimethoprim, calcineurin inhibitors). Adjust or stop interacting agents and intensify laboratory monitoring when co‑administration is unavoidable.

Document counseling on pregnancy risk, angioedema warning signs, and the laboratory monitoring plan in the chart; escalate to nephrology or vascular surgery if creatinine or potassium thresholds are crossed, or if renovascular disease or severe angioedema is suspected.