What is the recommended dose adjustment for an adult patient with hypertension or heart failure taking ramipril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

ARNI Dose Adjustment

The question asks about ARNI (Angiotensin Receptor-Neprilysin Inhibitor) dose adjustment, but the evidence provided only addresses ramipril (an ACE inhibitor), not ARNIs like sacubitril/valsartan. Since no ARNI-specific evidence is available, I cannot provide evidence-based recommendations for ARNI dose adjustment.

Important Clarification

• ARNIs (e.g., sacubitril/valsartan) and ACE inhibitors (e.g., ramipril) are distinct drug classes that should never be combined due to increased risk of angioedema 1
• A mandatory 36-hour washout period is required when switching from an ACE inhibitor to an ARNI to avoid this serious adverse effect
• The evidence provided addresses only ACE inhibitor dosing, not ARNI management

If You Meant Ramipril (ACE Inhibitor) Dose Adjustment

For Hypertension

Start ramipril at 2.5 mg once daily and titrate according to blood pressure response, with a usual maintenance range of 2.5-20 mg per day administered as a single dose or in two divided doses 2.

• If antihypertensive effect diminishes toward the end of the dosing interval with once-daily dosing, increase the dose or switch to twice-daily administration 2
• If blood pressure remains uncontrolled on ramipril alone, add a diuretic 2
• Target doses from clinical trials: 5 mg twice daily or 10 mg once daily 3

For Heart Failure Post-Myocardial Infarction

Begin with ramipril 2.5 mg twice daily (5 mg total per day), or 1.25 mg twice daily if the patient becomes hypotensive 2.

• After one week at the starting dose, increase toward a target of 5 mg twice daily if tolerated, with dose increases spaced approximately 3 weeks apart 2
• Observe the patient under medical supervision for at least 2 hours after the initial dose, and until blood pressure stabilizes for an additional hour 2
• Reduce concomitant diuretic doses when possible to minimize hypotension risk 2

Renal Impairment Adjustments

For patients with creatinine clearance >40 mL/min, use usual dosing regimens; for worse impairment, use 25% of the usual dose 2.

• Hypertension with renal impairment: Start at 1.25 mg once daily, titrate upward to a maximum of 5 mg total daily dose 2
• Heart failure with renal impairment: Start at 1.25 mg once daily, may increase to 1.25 mg twice daily, up to a maximum of 2.5 mg twice daily 2
• Monitor renal function and potassium within 1-2 weeks of initiation or dose changes 3

Special Circumstances

For volume depletion or suspected renal artery stenosis, initiate at 1.25 mg once daily and adjust according to blood pressure response 2.

• Exercise caution with systolic blood pressure <80 mm Hg, serum creatinine >3 mg/dL, bilateral renal artery stenosis, or serum potassium >5.0 mEq/L 3
• An increase in creatinine up to 50% above baseline, or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 3
• Hyperkalemia up to 5.5 mEq/L is generally acceptable, though levels >6.0 mEq/L require intervention 3

Monitoring Requirements

• Check blood pressure, renal function (creatinine), and electrolytes (potassium) 1-2 weeks after each dose increment 3
• Recheck at 3 months, then at regular 6-month intervals 3
• Avoid concomitant potassium supplements, potassium-sparing diuretics, or NSAIDs which increase hyperkalemia risk 2, 4

Common Pitfalls

• Never combine two ACE inhibitors - this significantly increases risk of hypotension, hyperkalemia, and renal dysfunction without additional benefit 1
• Asymptomatic hypotension does not require treatment discontinuation 3
• Persistent dry cough rarely requires discontinuation; if truly intolerable and proven ACE inhibitor-related, consider switching to an ARB 3
• Abrupt withdrawal can lead to clinical deterioration and should be avoided 3