For an adult hypertensive patient, how should I select the initial antihypertensive medication based on age, race (e.g., Black or African‑American), comorbid conditions such as diabetes, chronic kidney disease (estimated glomerular filtration rate <60 mL/min), heart failure with reduced ejection fraction, coronary artery disease, pregnancy, baseline blood‑pressure level, and any contraindications to drug classes?

Selecting Initial Antihypertensive Therapy

For most adults with hypertension, initial therapy should include a thiazide-type diuretic, calcium channel blocker (CCB), ACE inhibitor (ACEI), or angiotensin receptor blocker (ARB), with specific selection guided by race, comorbidities, and contraindications. 1

General Population (Non-Black Adults)

• Start with any of the four first-line classes: thiazide-type diuretic, CCB, ACEI, or ARB, as all have demonstrated reduction in cardiovascular and renal outcomes. 1, 2
• Combination therapy is required in most patients to achieve blood pressure targets, particularly when starting BP is ≥20/10 mmHg above goal. 1
• Single-pill combinations are strongly preferred when using dual therapy, as they significantly improve medication adherence and persistence. 1

Black or African-American Patients

• Initial therapy should include a thiazide-type diuretic or CCB rather than an ACEI or ARB, as these classes are more effective in lowering BP in Black populations due to lower renin activity. 1, 2
• Two or more antihypertensive medications are recommended to achieve BP target <130/80 mmHg in most Black adults with hypertension. 1
• If CKD with proteinuria is present as a single-agent indication, an ACEI or ARB should be initial therapy; otherwise, thiazide or CCB remains preferred. 1

Patients with Diabetes Mellitus

• For non-Black patients with diabetes: initiate with thiazide-type diuretic, CCB, ACEI, or ARB—no specific class preference unless CKD is present. 1, 2
• For Black patients with diabetes: initial therapy should be thiazide-type diuretic or CCB. 1
• Target BP is <140/90 mmHg (JNC 8) or <130/80 mmHg (ACC/AHA 2017), with the lower target preferred for higher-risk patients. 1

Chronic Kidney Disease (eGFR <60 mL/min or Proteinuria)

• Initiate or include an ACEI or ARB to improve kidney outcomes, regardless of race or diabetes status. 1, 2
• For Black patients with CKD: if BP control requires only one agent and proteinuria is present, start with ACEI or ARB; otherwise, add ACEI/ARB to thiazide or CCB. 1
• Target BP is <140/90 mmHg for all age groups with CKD. 1
• Monitor serum potassium and creatinine 2–4 weeks after initiating ACEI or ARB, especially when combined with other agents. 3

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Initiate with ACEI or ARB as the cornerstone of therapy, combined with a beta-blocker for mortality benefit. 1
• Add a thiazide-type diuretic or CCB if additional BP lowering is needed after optimizing ACEI/ARB and beta-blocker doses. 1
• Avoid non-dihydropyridine CCBs (diltiazem, verapamil) due to negative inotropic effects. 1

Coronary Artery Disease

• Beta-blockers are indicated post-myocardial infarction or for angina management, but are not first-line for uncomplicated hypertension. 1
• Combine beta-blocker with ACEI or ARB plus thiazide diuretic or CCB to achieve BP targets. 1

Pregnancy

• Avoid ACEIs, ARBs, and direct renin inhibitors due to teratogenicity and fetal harm. 1
• Preferred agents include methyldopa, labetalol, and long-acting nifedipine, with specific obstetric guidance required. 1

Age-Based Considerations

Adults <60 Years

• Target BP <140/90 mmHg for systolic (expert opinion) and diastolic (strong evidence). 2
• Initiate therapy at BP ≥140/90 mmHg or at 130–139/80–89 mmHg if 10-year ASCVD risk ≥10% or established CVD. 1

Adults ≥60 Years

• Target BP <150/90 mmHg (JNC 8) or <130/80 mmHg (ACC/AHA 2017, ESC/ESH 2018). 1, 2
• For fit elderly <80 years, target systolic <140 mmHg; for those ≥80 years, systolic 140–150 mmHg is acceptable. 1
• Frail elderly require individualized targets based on tolerance and functional status. 1

Baseline Blood Pressure Level

Stage 1 Hypertension (140–159/90–99 mmHg)

• Start with monotherapy if no compelling indications; advance to dual therapy if target not achieved in 2–4 weeks. 1, 2

Stage 2 Hypertension (≥160/100 mmHg or ≥20/10 mmHg Above Target)

• Initiate with two-drug combination therapy from different classes, preferably as a single-pill combination. 1
• For Black patients with stage 2 hypertension, dual therapy with thiazide + CCB is particularly effective. 1

Contraindications and Special Situations

Avoid ACEIs/ARBs if:

• Pregnancy or planning pregnancy 1
• History of angioedema 1
• Bilateral renal artery stenosis 1
• Severe hyperkalemia (K+ >5.5 mEq/L) 1

Avoid Beta-Blockers as First-Line if:

• No compelling indication (angina, post-MI, HFrEF, atrial fibrillation) 1
• Asthma or severe COPD 1
• Peripheral arterial disease with claudication 1

Avoid Thiazide Diuretics if:

• Gout or recurrent hyperuricemia 1
• Severe hyponatremia 1

Avoid Non-Dihydropyridine CCBs if:

• Heart failure with reduced ejection fraction 1
• Second- or third-degree AV block without pacemaker 1

Critical Pitfalls to Avoid

• Never combine an ACEI with an ARB (dual RAS blockade increases hyperkalemia and acute kidney injury without cardiovascular benefit). 1
• Do not use beta-blockers as initial therapy in uncomplicated hypertension, as they are less effective than thiazides or CCBs for stroke prevention. 1
• Do not delay combination therapy in patients with BP ≥20/10 mmHg above target or stage 2 hypertension. 1
• Verify medication adherence before assuming treatment failure, as non-adherence is the most common cause of apparent resistance. 1, 3
• Confirm true hypertension with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) before escalating therapy. 1
• Screen for secondary hypertension if BP remains severely elevated (≥180/110 mmHg) or resistant to triple therapy. 1, 3

Monitoring and Follow-Up

• Reassess BP within 2–4 weeks after initiating or modifying therapy. 1, 3
• Achieve target BP within 3 months of treatment initiation or modification. 1, 3
• Check serum potassium and creatinine 2–4 weeks after starting ACEI, ARB, or diuretic therapy. 3
• Reinforce lifestyle modifications (sodium <2 g/day, DASH diet, weight loss, exercise, alcohol limitation) as adjunctive therapy providing 10–20 mmHg systolic reduction. 1, 3