What is the recommended dose of Ramipril (Angiotensin-Converting Enzyme inhibitor) for adults with hypertension?

Ramipril Dosing for Adult Hypertension

For adults with hypertension, start ramipril at 2.5 mg once daily and titrate up to a usual maintenance range of 2.5-20 mg daily (given once daily or divided twice daily), with most patients achieving control on ≤5 mg once daily. 1

Initial Dosing Strategy

• Begin with 2.5 mg once daily in patients not receiving a diuretic, as this is the FDA-approved starting dose for hypertension 1
• Use 1.25 mg once daily as the initial dose in patients with:
  • Renal impairment (creatinine clearance <40 mL/min) 1
  • Volume depletion or suspected renal artery stenosis 1
  • Concurrent diuretic therapy (consider reducing diuretic dose first) 1

Dose Titration and Maintenance

• Titrate dosage upward based on blood pressure response, with the usual maintenance range being 2.5-20 mg per day 1
• Most patients respond to ≤5 mg once daily: In a large prospective study of 591 hypertensive patients, 41% required only 2.5 mg and 81% achieved control with ≤5 mg once daily 2
• Consider twice-daily dosing if the antihypertensive effect diminishes toward the end of the 24-hour dosing interval 1
• Maximum dose is 20 mg daily for hypertension 1

Blood Pressure Targets

• Target BP <130/80 mm Hg for all adults with hypertension, as recommended by the 2017 ACC/AHA guidelines 3
• This target applies regardless of ASCVD risk once antihypertensive therapy is initiated 3
• For patients with stable ischemic heart disease and hypertension, the same <130/80 mm Hg target is recommended 3

Combination Therapy Approach

• Add a thiazide diuretic if ramipril monotherapy is insufficient to control blood pressure 1
• For stage 2 hypertension (BP ≥20/10 mm Hg above target), initiate treatment with two first-line agents from different classes, which can include ramipril combined with a thiazide diuretic or calcium channel blocker 3
• The combination of ramipril 5 mg with hydrochlorothiazide 25 mg has demonstrated superior blood pressure reduction compared to either component alone 4

Monitoring and Follow-Up

• Reassess monthly after initiating therapy until blood pressure control is achieved 3
• Monitor serum creatinine and potassium at baseline and during treatment, particularly when combining with diuretics or in patients with renal impairment 1
• Once BP target is achieved, follow-up can be extended to every 3-6 months 3

Special Considerations and Pitfalls

• Avoid combining ramipril with other ACE inhibitors or ARBs, as this increases adverse effects without additional benefit 5
• First-dose hypotension risk: Observe patients for at least 2 hours after the initial dose, especially in volume-depleted patients or those on high-dose diuretics 1
• Renal dose adjustment: In patients with creatinine clearance <40 mL/min, 25% of the usual dose produces full therapeutic levels, with a maximum of 5 mg daily for hypertension 1
• Pregnancy contraindication: Ramipril is absolutely contraindicated in pregnancy; ensure women of childbearing age use reliable contraception 5

Dose-Response Evidence

• Clinical trials demonstrate effectiveness rates of 28% at 1.25 mg, 52% at 2.5 mg, 70% at 5 mg, and 78% at 10 mg of ramipril monotherapy 6
• In patients already on thiazide diuretics, adding ramipril showed effectiveness in 48% at 2.5 mg and 70% at 5 mg 6
• The 2.5-10 mg daily range has been validated across multiple controlled trials as effective for blood pressure reduction with once-daily dosing 7, 8