What to add to amlodipine for a 58-year-old patient with impaired renal function (Serum Creatinine 2.1) and uncontrolled hypertension?

Add an ACE Inhibitor or ARB to Amlodipine

For this 58-year-old patient with impaired renal function (SCr 2.1) and uncontrolled hypertension on amlodipine monotherapy, add an ACE inhibitor (such as lisinopril 10 mg daily) or an ARB (such as losartan 50 mg daily) as the second antihypertensive agent. 1

Rationale for ACE Inhibitor/ARB Addition

• The International Society of Hypertension guidelines recommend that for patients already on a calcium channel blocker like amlodipine, the next step should be adding an ACE inhibitor or ARB to provide complementary mechanisms of action—vasodilation through calcium channel blockade and renin-angiotensin system inhibition 1

• This combination is particularly beneficial for patients with chronic kidney disease, as ACE inhibitors and ARBs provide renoprotective effects beyond blood pressure reduction alone 1

• The combination of amlodipine with an ACE inhibitor has demonstrated superior blood pressure control compared to either agent alone in patients with diabetes, chronic kidney disease, or heart failure 1

Specific Medication Recommendations

• Start lisinopril 10 mg once daily or losartan 50 mg once daily as the initial dose, with plan to titrate upward if blood pressure remains uncontrolled 1

• If blood pressure remains uncontrolled after optimizing the ACE inhibitor/ARB dose (lisinopril up to 40 mg or losartan up to 100 mg), then add a thiazide-like diuretic as the third agent 2, 1

Critical Monitoring in Renal Impairment

• Check serum creatinine and potassium within 1-2 weeks after initiating the ACE inhibitor or ARB, as patients with baseline renal impairment (SCr 2.1) are at higher risk for hyperkalemia and acute kidney injury 2, 1

• An increase in serum creatinine up to 30% from baseline is acceptable and does not require discontinuation, as this reflects hemodynamic changes rather than true kidney injury 1

• Monitor for hyperkalemia closely—hold or reduce the dose if potassium rises above 5.5 mEq/L 1

Amlodipine Safety in Renal Dysfunction

• Amlodipine is safe and effective in patients with renal impairment, with studies showing significant blood pressure reduction without aggravation of renal dysfunction 3, 4

• Amlodipine has low renal clearance (7 mL/min/mg) and does not accumulate in patients with renal impairment, making dose adjustment unnecessary 5, 3

• In clinical studies of hypertensive patients with renal dysfunction (serum creatinine ≥1.5 mg/dL), amlodipine 2.5-5 mg daily achieved target blood pressure reduction in 80% of patients with minimal side effects 3, 4

Blood Pressure Targets and Timeline

• Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg for patients with chronic kidney disease 1

• Reassess blood pressure within 2-4 weeks after adding the ACE inhibitor/ARB, with the goal of achieving target blood pressure within 3 months of treatment modification 1

If Blood Pressure Remains Uncontrolled on Dual Therapy

• Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg daily preferred over hydrochlorothiazide) as the third agent to achieve guideline-recommended triple therapy 2, 1

• The combination of ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic represents the evidence-based triple therapy targeting three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 2, 1

Critical Pitfall to Avoid

• Do not add a thiazide diuretic as the second agent before trying an ACE inhibitor or ARB first, as the renoprotective benefits of RAS blockade are particularly important in this patient with baseline renal impairment (SCr 2.1) 1

• Never combine an ACE inhibitor with an ARB, as this dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1