What are the recommended initial medications for managing hypertension?

Initial Antihypertensive Medications for Hypertension Management

For most patients with newly diagnosed hypertension, start with one of four first-line drug classes: ACE inhibitors (e.g., lisinopril 10 mg daily), ARBs (e.g., losartan 50 mg daily), thiazide-like diuretics (e.g., chlorthalidone 12.5-25 mg daily), or long-acting dihydropyridine calcium channel blockers (e.g., amlodipine 5 mg daily), with selection based on blood pressure severity, comorbidities, and race. 1, 2

Treatment Algorithm Based on Blood Pressure Severity

Blood Pressure 130-159/80-99 mmHg

• Start with a single agent from the four first-line drug classes 1, 2, 3
• For patients with diabetes, chronic kidney disease, or established cardiovascular disease at BP 130-139/80-89 mmHg, initiate pharmacologic therapy immediately rather than waiting for lifestyle modifications alone 1, 2, 3

Blood Pressure ≥160/100 mmHg

• Initiate two antihypertensive medications simultaneously to achieve more rapid blood pressure control 1, 2
• Single-pill combination therapy improves medication adherence and should be considered 1, 2

Medication Selection Based on Patient Characteristics

Non-Black Patients Without Specific Comorbidities

• First choice: ACE inhibitor or ARB 2, 3
• Lisinopril 10 mg once daily is the recommended starting dose for most adults 4
• Alternative: Thiazide-like diuretic (chlorthalidone preferred over hydrochlorothiazide) or long-acting dihydropyridine calcium channel blocker 1, 5

Black Patients

• First choice: Calcium channel blocker or thiazide-like diuretic 1, 2, 3
• These drug classes demonstrate superior efficacy in Black patients compared to ACE inhibitors or ARBs as monotherapy 1, 2
• If combination therapy needed, add an ACE inhibitor or ARB to the calcium channel blocker or diuretic 1

Patients with Diabetes

• First choice: ACE inhibitor or ARB 1, 2
• For diabetes with coronary artery disease, ACE inhibitors or ARBs are specifically recommended as first-line therapy 1, 2
• Add calcium channel blocker or thiazide-like diuretic if blood pressure goal not achieved with monotherapy 1, 2
• Target blood pressure is <130/80 mmHg 1

Patients with Chronic Kidney Disease or Albuminuria

• Mandatory first choice: ACE inhibitor or ARB 1, 2, 3
• For albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), ACE inhibitors or ARBs are strongly recommended because they reduce albuminuria more effectively than other antihypertensive classes 1, 2
• Target dose: lisinopril 20-40 mg daily or losartan 50-100 mg daily 2
• For eGFR >30 mL/min/1.73 m², target systolic BP 120-129 mmHg if tolerated 1
• Dose adjustment required for renal impairment: For creatinine clearance 10-30 mL/min, start lisinopril at 5 mg daily; for creatinine clearance <10 mL/min or hemodialysis, start at 2.5 mg daily 4

Patients with Coronary Artery Disease

• First choice: ACE inhibitor or ARB 1, 2
• Add beta-blocker if prior myocardial infarction, active angina, or heart failure with reduced ejection fraction 1, 2
• Beta-blockers are NOT recommended as first-line therapy for blood pressure lowering alone without these specific cardiac indications 1, 2

Patients with Heart Failure

• For heart failure with reduced ejection fraction (HFrEF): ACE inhibitor (or ARB if ACE inhibitor not tolerated), beta-blocker, diuretic, and mineralocorticoid receptor antagonist, plus SGLT2 inhibitor 1
• Starting dose for heart failure: lisinopril 5 mg once daily, or 2.5 mg if hyponatremia (serum sodium <130 mEq/L) present 4
• For heart failure with preserved ejection fraction (HFpEF): SGLT2 inhibitors recommended; ARBs or mineralocorticoid receptor antagonists may be considered 1

Effective Two-Drug Combinations

When dual therapy is needed, use one of these evidence-based combinations: 1, 2

• Thiazide diuretic + ACE inhibitor
• Thiazide diuretic + ARB
• Calcium channel blocker + ACE inhibitor
• Calcium channel blocker + ARB

For patients already on an ACE inhibitor or ARB who need additional therapy, add hydrochlorothiazide 12.5 mg daily 4, 6

Resistant Hypertension (Not Controlled on Three Drugs)

• Definition: Blood pressure ≥140/90 mmHg despite appropriate lifestyle management plus a diuretic and two other antihypertensive drugs at adequate doses 1
• Recommended approach: Add low-dose spironolactone (mineralocorticoid receptor antagonist) to existing triple therapy 1
• Alternative if spironolactone not tolerated: Eplerenone, amiloride, higher-dose thiazide diuretic, or loop diuretic 1
• Reinforce sodium restriction (<1500 mg/day) as this significantly enhances medication efficacy 1

Critical Pitfalls to Avoid

Dangerous Drug Combinations

• NEVER combine ACE inhibitor + ARB - this increases risk of hyperkalemia, syncope, and acute kidney injury without providing additional cardiovascular benefit 1, 3
• NEVER combine ACE inhibitor or ARB + direct renin inhibitor - similar increased adverse event risk without benefit 1, 3

Inappropriate First-Line Choices

• Do NOT use beta-blockers as first-line therapy unless specific indication exists (prior MI, active angina, heart failure with reduced ejection fraction) 1, 2
• Do NOT delay medication initiation in high-risk patients or those with BP ≥160/100 mmHg to complete cardiovascular risk assessment 2, 3

Monitoring Errors

• Do NOT forget to monitor serum creatinine/eGFR and potassium at least annually when using ACE inhibitors, ARBs, or diuretics 3
• Do NOT use immediate-release nifedipine for hypertensive urgencies due to unpredictable blood pressure drops 7, 8

Target Blood Pressure Goals

• Most adults <65 years: <130/80 mmHg 1, 2, 9, 5
• Adults ≥65 years: Systolic <130 mmHg if tolerated, individualized based on frailty 2, 5
• Patients with diabetes: <130/80 mmHg 1
• Patients with chronic kidney disease: Systolic 120-129 mmHg if eGFR >30 mL/min/1.73 m² and tolerated 1
• Patients with known cardiovascular disease: Systolic <130 mmHg 9, 3

Titration and Follow-Up Strategy

• Start at low dose and increase after 4 weeks if blood pressure goal not achieved 2
• Monthly follow-up after initiation or medication changes until target BP reached 3
• Every 3-5 months once blood pressure controlled 3
• Achieve target within 3 months of initiating therapy 2
• Maximum dose lisinopril: 40 mg daily (doses up to 80 mg studied but show no greater effect) 4