In an adult patient with hypertension, how do I decide whether to start an ACE inhibitor, an ARB, or a thiazide diuretic?

How to Choose Between ARB, ACE Inhibitor, or Thiazide Diuretic for Hypertension

For most adults with uncomplicated hypertension, start with a thiazide-type diuretic—specifically chlorthalidone—because it has the strongest evidence for preventing heart failure and stroke compared to ACE inhibitors and ARBs. 1

Decision Algorithm Based on Patient Characteristics

Step 1: Assess Blood Pressure Stage and Cardiovascular Risk

Stage 1 Hypertension (130-139/80-89 mmHg):

• Start with single-agent monotherapy and titrate before adding a second drug 1, 2
• Initiate pharmacologic therapy only if 10-year ASCVD risk ≥10% or established cardiovascular disease 1, 2

Stage 2 Hypertension (≥140/90 mmHg or >20/10 mmHg above goal):

• Start with two-drug combination from different classes, preferably as a single pill 1, 2
• Preferred combinations: thiazide + (ACE inhibitor or ARB) OR calcium channel blocker + (ACE inhibitor or ARB) 2, 3

Step 2: Apply Population-Specific Selection Criteria

Black Patients (without heart failure or CKD):

• First choice: Thiazide diuretic (chlorthalidone) or calcium channel blocker 1
• ACE inhibitors are 15% less effective for stroke prevention and 19% less effective for heart failure prevention in this population 1
• ARBs cause less cough and angioedema than ACE inhibitors but offer no proven cardiovascular advantage over thiazides or calcium channel blockers 1

Patients with Diabetes Mellitus:

• First choice: ACE inhibitor or ARB to protect renal function 1, 2
• This is mandatory first-line therapy when albuminuria ≥300 mg/day is present 1, 2
• Target blood pressure <130/80 mmHg 2, 3

Patients with Chronic Kidney Disease (Stage 3+ or albuminuria):

• First choice: ACE inhibitor or ARB to slow eGFR decline and reduce proteinuria 1, 2
• Thiazide diuretics remain effective even when eGFR <30 mL/min/1.73 m² and should not be avoided 1
• Monitor potassium and creatinine within 1-2 weeks of starting therapy 1

Patients with Heart Failure with Reduced Ejection Fraction:

• First choice: ACE inhibitor or ARB + beta-blocker + diuretic 2, 3
• This triple combination is guideline-directed medical therapy 2

Patients with Stable Ischemic Heart Disease or Post-MI:

• First choice: Beta-blocker + ACE inhibitor or ARB 2, 3
• Continue beta-blocker for at least 3 years post-MI 3

General Adult Population (non-Black, no compelling indications):

• First choice: Thiazide diuretic (chlorthalidone 12.5-25 mg daily) 1, 4
• In the ALLHAT trial of >50,000 patients, chlorthalidone reduced heart failure by 38% versus amlodipine and stroke by 15% versus lisinopril 1, 4
• Second choice: Long-acting calcium channel blocker if thiazide not tolerated 1
• Third choice: ACE inhibitor or ARB when albuminuria or coronary disease present 1

Step 3: Recognize When NOT to Use Each Class

Do NOT use ACE inhibitors or ARBs:

• In pregnancy (absolutely contraindicated due to fetal toxicity) 2, 3
• When combining both an ACE inhibitor AND an ARB together (increases hyperkalemia and acute kidney injury risk without benefit) 1
• As first-line in Black patients without CKD or heart failure (30-36% less effective for stroke prevention) 1

Do NOT use thiazide diuretics:

• When gout is active or recurrent 1
• Exercise caution in patients at risk for hypokalemia, but this can be mitigated with potassium-sparing diuretics 4

Do NOT use beta-blockers as first-line:

• In uncomplicated hypertension, especially patients >60 years (36% less effective than calcium channel blockers and 30% less effective than thiazides for stroke prevention) 1, 2

Critical Implementation Details

Monitoring Requirements:

• After starting ACE inhibitor, ARB, or diuretic: check creatinine, eGFR, and potassium within 1-2 weeks, after each dose increase, and annually 1, 3
• An increase in creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable 3
• Schedule monthly follow-up until blood pressure target achieved, then every 3-5 months 1, 2, 3

Target Blood Pressure:

• General population: <130/80 mmHg 1, 2, 3
• Avoid lowering diastolic below 60-70 mmHg in high-risk patients 3

Common Pitfalls to Avoid:

• Using hydrochlorothiazide <25 mg daily as monotherapy (unproven efficacy compared to chlorthalidone) 2, 4
• Delaying combination therapy in stage 2 hypertension (increases cardiovascular risk) 1, 2, 3
• Failing to use single-pill combinations when appropriate (reduces adherence) 2, 3
• Starting beta-blockers first-line without compelling cardiac indication 1, 2