When should antihypertensive medication be started and which first‑line agent should be selected based on blood pressure thresholds, established cardiovascular disease, diabetes, chronic kidney disease, 10‑year atherosclerotic cardiovascular disease risk, race, and other patient characteristics?

Hypertension Drug Initiation Guidelines

Blood Pressure Thresholds for Medication Initiation

Start antihypertensive medication immediately in all adults with confirmed blood pressure ≥140/90 mmHg (Stage 2 hypertension), regardless of cardiovascular risk. 1, 2

For Stage 1 hypertension (130-139/80-89 mmHg), medication initiation depends on cardiovascular risk stratification:

High-Risk Patients (Start Medication Immediately at BP ≥130/80 mmHg)

• Established cardiovascular disease (prior MI, stroke, coronary revascularization, heart failure, peripheral artery disease) 1, 2, 3
• 10-year ASCVD risk ≥10% using ACC/AHA Pooled Cohort Equations 1, 2, 3
• Diabetes mellitus (automatically high-risk category) 1, 2
• Chronic kidney disease (eGFR <60 mL/min/1.73 m² or albuminuria ≥30 mg/g) 1, 2
• Age ≥65 years 2, 3

Low-Risk Patients (Lifestyle Modifications First)

• BP 130-139/80-89 mmHg without high-risk features: Implement lifestyle modifications for 3-6 months 1, 2, 3
• Initiate medication only if BP remains ≥140/90 mmHg after lifestyle intervention trial 1, 2

First-Line Medication Selection

Standard First-Line Agents (Choose Based on Patient Characteristics)

For non-Black patients without compelling indications:

• Start with ACE inhibitor or ARB as initial therapy 1, 4
• Alternative first-line: thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) 1, 4
• Alternative first-line: dihydropyridine calcium channel blocker (amlodipine) 1, 4

For Black patients:

• Start with ARB plus dihydropyridine calcium channel blocker OR calcium channel blocker plus thiazide-like diuretic 1
• ACE inhibitors/ARBs are less effective as monotherapy in Black patients 1

Compelling Indications (Override Standard Selection)

Diabetes mellitus:

• First-line: ACE inhibitor or ARB at maximum tolerated dose 1, 5
• Target BP <130/80 mmHg 1, 6
• If BP ≥150/90 mmHg, start with two medications immediately (single-pill combination preferred) 1

Chronic kidney disease with albuminuria:

• UACR ≥300 mg/g: ACE inhibitor or ARB mandatory as first-line 1
• UACR 30-299 mg/g: ACE inhibitor or ARB strongly recommended 1
• Monitor serum creatinine and potassium within 7-14 days after initiation 1, 5

Established coronary artery disease:

• First-line: ACE inhibitor or ARB 1, 3

Heart failure with reduced ejection fraction:

• Beta-blocker indicated (not for hypertension alone) 1

Prior myocardial infarction:

• Beta-blocker indicated 1

Race-Based Considerations

Black patients:

• Require combination therapy more often 1
• Start with ARB + calcium channel blocker or calcium channel blocker + thiazide diuretic 1
• ACE inhibitors/ARBs less effective as monotherapy but still appropriate with albuminuria 1

Non-Black patients:

• Start with ACE inhibitor or ARB monotherapy 1
• Add calcium channel blocker or thiazide diuretic as second agent 1

Initial Monotherapy vs. Combination Therapy

Start with two medications immediately when:

• BP ≥160/100 mmHg (≥20/10 mmHg above goal) 1, 3
• BP ≥150/90 mmHg in patients with diabetes 1
• Stage 2 hypertension in most patients 1
• Use single-pill combinations to improve adherence 1

Start with monotherapy when:

• Low-risk Stage 1 hypertension (130-139/80-89 mmHg) 1
• Age >80 years or frail patients 1
• BP only modestly elevated above goal 1

Treatment Targets

Target BP <130/80 mmHg for:

• All adults with hypertension regardless of age or comorbidities 1, 2, 3
• Patients with diabetes mellitus 1, 6
• Patients with chronic kidney disease 1, 3

Individualize target for:

• Adults >80 years based on frailty (may accept higher targets if poorly tolerated) 1, 3

Medication Titration Strategy

Step 1: Start first-line agent at low dose 1

Step 2: Increase to full dose if BP not at goal 1

Step 3: Add second agent from different class (thiazide diuretic or calcium channel blocker) 1, 4

Step 4: Add third agent if still not at goal 1

Step 5: Add spironolactone (mineralocorticoid receptor antagonist) as fourth-line agent; alternatives include amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 1

Critical Monitoring Parameters

Within 2-4 weeks of initiating ACE inhibitor/ARB or diuretic:

• Serum creatinine and potassium 1, 5
• Expect creatinine increase up to 30% (acceptable) 1

Monthly follow-up until BP controlled:

• Office BP measurement 3
• Assess medication adherence 1
• Titrate medications to achieve target 3

After BP controlled:

• Follow-up every 3-6 months 3

Common Pitfalls to Avoid

Do not combine:

• ACE inhibitor + ARB (increases hyperkalemia risk without additional benefit) 1, 4
• ACE inhibitor or ARB + direct renin inhibitor 1

Do not use as first-line:

• Beta-blockers (unless compelling indication: prior MI, heart failure, active angina) 1, 4
• Short-acting nifedipine (contraindicated for hypertensive emergencies) 3

Do not delay treatment:

• In Stage 2 hypertension, start medication immediately—do not wait for lifestyle modification trial 1
• In high-risk Stage 1 hypertension, start medication at first visit 1, 2

Monitor for hyperkalemia when:

• Using ACE inhibitor or ARB in patients with eGFR <60 mL/min/1.73 m² 1, 5
• Adding mineralocorticoid receptor antagonist to ACE inhibitor/ARB 1
• Check potassium within 7-14 days and regularly thereafter 1, 5