In a smoker with uncontrolled hypertension on amlodipine 5 mg, should the amlodipine be increased to 10 mg or should an angiotensin‑converting enzyme inhibitor (ACE‑I) or angiotensin receptor blocker (ARB) be added?

Add an ACE Inhibitor or ARB to Amlodipine 5 mg

For a smoker with uncontrolled hypertension on amlodipine 5 mg, adding an ACE inhibitor or ARB is the preferred next step rather than simply increasing amlodipine to 10 mg. 1

Rationale for Combination Therapy Over Dose Escalation

• Adding a second agent from a different class (ACE inhibitor or ARB) provides complementary mechanisms—renin-angiotensin system blockade plus calcium-channel vasodilation—and achieves blood pressure control more rapidly and effectively than dose escalation alone. 1
• The combination of amlodipine with an ACE inhibitor or ARB has demonstrated superior blood pressure control compared to either agent alone, particularly in patients with diabetes, chronic kidney disease, or heart failure. 1
• Uptitrating amlodipine from 5 mg to 10 mg yields only an additional 1.6/3.3 mmHg reduction, whereas adding an ACE inhibitor or ARB produces a substantially larger systolic reduction of approximately 10–20 mmHg. 1

When to Consider Amlodipine Dose Escalation

• Increasing amlodipine to 10 mg is reasonable only if the patient has documented intolerance or contraindication to both ACE inhibitors and ARBs—an uncommon scenario. 1
• Titration of amlodipine from 5 mg to 10 mg does significantly decrease blood pressure (by approximately 12 mmHg systolic and 7 mmHg diastolic), but this approach is less effective than adding a second drug class. 2
• Even after uptitration to 10 mg, a second agent should be added if blood pressure remains ≥140/90 mmHg after 4 weeks. 1

Specific Drug Selection

• For non-Black patients, start with an ACE inhibitor (lisinopril 10–20 mg daily) or ARB (losartan 50–100 mg daily) as the second agent. 1, 3
• For Black patients, the combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB. 1
• The combination of amlodipine with an ACE inhibitor may also attenuate amlodipine-related peripheral edema. 1

Blood Pressure Targets and Monitoring

• Target blood pressure is <140/90 mmHg minimum, ideally <130/80 mmHg for most patients. 1, 4
• Reassess blood pressure within 2–4 weeks after adding the second agent, with the goal of achieving target within 3 months. 1, 4
• Monitor for specific side effects: cough with ACE inhibitors, hyperkalemia with both ACE inhibitors and ARBs, and acute kidney injury with both classes. 1
• Check serum potassium and creatinine 2–4 weeks after initiating an ACE inhibitor or ARB. 1, 4

Addressing Smoking as a Risk Factor

• Smoking causes an acute increase in blood pressure and heart rate, persisting for more than 15 minutes after smoking one cigarette, through sympathetic nervous system stimulation. 5
• Ambulatory blood pressure monitoring has shown that both untreated hypertensive and normotensive smokers present higher daily blood pressure values than non-smokers. 5
• Smoking cessation should be strongly advised as part of comprehensive lifestyle modifications, as those who quit smoking before middle age typically have a life expectancy not different from lifelong non-smokers. 5

Escalation to Triple Therapy

• If blood pressure remains uncontrolled after optimizing doses of amlodipine plus ACE inhibitor/ARB, add a thiazide-like diuretic (chlorthalidone 12.5–25 mg or hydrochlorothiazide 25 mg daily) as the third agent. 1
• The combination of ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic represents guideline-recommended triple therapy with complementary mechanisms targeting volume reduction, vasodilation, and renin-angiotensin system blockade. 1

Critical Pitfalls to Avoid

• Do not combine an ACE inhibitor with an ARB, as dual renin-angiotensin system blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 3
• Do not rely solely on dose escalation of amlodipine as the primary strategy when combination therapy is more effective. 1
• Do not delay treatment intensification—uncontrolled hypertension requires prompt action within 2–4 weeks to reduce cardiovascular risk. 1
• Do not assume treatment failure without first confirming medication adherence and ruling out secondary causes of hypertension. 1, 4