How should I choose the initial antihypertensive medication for a newly diagnosed adult patient, considering age, race, comorbidities (diabetes, chronic kidney disease, coronary artery disease, heart failure, prior stroke, pregnancy), baseline blood pressure, estimated glomerular filtration rate, contraindications, drug interactions, cost, and patient preference?

Choosing Initial Antihypertensive Therapy for Newly Diagnosed Hypertension

For most newly diagnosed hypertensive patients, start with a thiazide-type diuretic, calcium-channel blocker (CCB), ACE inhibitor (ACEI), or angiotensin-receptor blocker (ARB), but prioritize thiazide diuretics or CCBs in Black patients, and reserve ACEIs/ARBs for patients with diabetes, chronic kidney disease with proteinuria, heart failure, or coronary artery disease. 1, 2

Step 1: Determine Blood Pressure Severity and Treatment Urgency

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

• Start with monotherapy using one of the four first-line agents (thiazide diuretic, CCB, ACEI, or ARB). 3, 1
• If BP target is not reached within 2-4 weeks, escalate to dual therapy. 1

Stage 2 Hypertension (≥160/100 mmHg or ≥20/10 mmHg above target)

• Begin immediately with two-drug combination therapy, preferably as a single-pill fixed-dose combination to improve adherence. 3, 1, 2
• The combination markedly improves medication persistence compared to separate pills. 1

Step 2: Apply Race-Based Selection Criteria

Black or African-American Patients

• Initiate therapy with a thiazide-type diuretic or CCB rather than an ACEI or ARB, because these classes produce greater BP reductions in this population due to lower renin activity. 1, 2
• For stage 2 hypertension in Black patients, dual therapy with thiazide diuretic plus CCB is especially effective. 1
• Exception: If proteinuria is present (indicating chronic kidney disease), start an ACEI or ARB regardless of race; otherwise add ACEI/ARB to a thiazide or CCB-based regimen. 1, 2

Non-Black Patients (White, Asian, Other)

• Any of the four first-line classes may be used (thiazide diuretic, CCB, ACEI, or ARB) with equal effectiveness for reducing cardiovascular and renal events. 1, 2
• When ACEI or ARB is combined with a thiazide diuretic in Black patients, inter-racial differences in BP reduction disappear. 2

Step 3: Screen for Compelling Indications (Comorbidities)

Diabetes Mellitus

• Non-Black patients: Any of the four first-line classes may be used; no specific class is favored unless CKD is also present. 1
• Black patients: Thiazide-type diuretic or CCB should be the initial choice. 1
• Target BP: <140/90 mmHg (acceptable) or <130/80 mmHg (preferred for higher cardiovascular risk). 3, 1, 2
• ACEIs or ARBs are mandatory if proteinuria or CKD is present. 2

Chronic Kidney Disease (eGFR <60 mL/min/1.73 m² or proteinuria)

• Initiate or add an ACEI or ARB to improve renal outcomes irrespective of race or diabetes status. 1, 2
• For Black patients with CKD and proteinuria, start an ACEI or ARB; otherwise add ACEI/ARB to a thiazide or CCB-based regimen. 1
• Target BP: <140/90 mmHg for all age groups with CKD. 1
• When eGFR is markedly reduced, loop diuretics are preferred over thiazides. 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Begin with an ACEI or ARB combined with a beta-blocker to obtain mortality benefit. 1, 2
• Add a thiazide-type diuretic or loop diuretic (depending on volume status) for additional BP lowering. 1, 2
• Avoid non-dihydropyridine CCBs (diltiazem, verapamil) because of negative inotropic effects and contraindication in HFrEF. 1, 2

Coronary Artery Disease or Post-Myocardial Infarction

• Beta-blocker plus ACEI or ARB form the foundational regimen. 1, 2
• Beta-blockers reduce mortality by approximately 28% after acute MI. 2
• Add a thiazide diuretic or CCB to achieve BP targets. 1

Prior Stroke or Transient Ischemic Attack

• Target systolic BP <140 mmHg to reduce recurrent stroke risk (absolute risk reduction 3.02%). 3
• Any of the four first-line classes may be used, with race-based selection as above. 1

Pregnancy or Pregnancy Potential

• ACEIs, ARBs, and direct renin inhibitors are absolutely contraindicated due to teratogenicity and fetal harm. 1, 2
• Preferred agents: Methyldopa, labetalol, or long-acting nifedipine with obstetric guidance. 1

Step 4: Age-Based Considerations

Adults <60 Years

• Initiate therapy at BP ≥140/90 mmHg, or at 130-139/80-89 mmHg when 10-year ASCVD risk ≥10% or established CVD is present. 1
• Target BP: <140/90 mmHg (standard) or <130/80 mmHg (intensive for high cardiovascular risk). 1, 2

Adults ≥60 Years

• Target BP <150/90 mmHg is acceptable, though <140/90 mmHg or <130/80 mmHg may be appropriate for fit elderly patients. 3, 1
• For patients <80 years, aim for systolic <140 mmHg; for those ≥80 years, a systolic range of 140-150 mmHg is acceptable. 1
• Thiazide diuretics or CCBs are preferred because they provide superior stroke prevention in elderly patients. 2
• Individualized assessment is particularly important in adults with multiple chronic conditions, several medications, or frailty. 3

Step 5: Check for Absolute Contraindications

Never Use ACEIs or ARBs if:

• Pregnancy or pregnancy potential (use methyldopa, labetalol, or nifedipine instead). 1, 2
• History of angioedema. 1, 2
• Bilateral renal-artery stenosis. 1, 2
• Severe hyperkalemia (K⁺ >5.5 mmol/L). 1

Never Use Beta-Blockers if:

• Severe asthma or high-grade atrioventricular block (grade 2-3) without a pacemaker. 2
• Avoid in COPD unless a compelling indication exists (angina, post-MI, HFrEF, atrial fibrillation). 1, 2

Never Use Thiazide Diuretics if:

• Gout or recurrent hyperuricemia. 1, 2
• Severe hyponatremia. 1

Never Use Non-Dihydropyridine CCBs (Diltiazem, Verapamil) if:

• Heart failure with reduced ejection fraction. 1, 2
• Second- or third-degree AV block without a pacemaker. 1

Step 6: Combination Therapy Strategy

When to Use Dual Therapy

• Stage 2 hypertension (≥160/100 mmHg) requires immediate dual therapy. 3, 1, 2
• Baseline BP ≥20/10 mmHg above target requires combination therapy in most patients. 1

Preferred Dual Combinations

• ACEI or ARB + CCB (first choice). 2
• ACEI or ARB + thiazide diuretic (equally effective). 2
• For Black patients with stage 2 hypertension, thiazide diuretic + CCB is especially effective. 1

Triple Therapy (if Dual Therapy Fails)

• ACEI or ARB + CCB + thiazide diuretic. 2

Combinations to Avoid

• Never combine ACEI + ARB (increases hyperkalemia and acute kidney injury without cardiovascular benefit). 1, 2
• Avoid adding beta-blocker as second or third agent unless a compelling indication exists (angina, post-MI, HFrEF, atrial fibrillation), as beta-blockers are less effective than CCBs or diuretics for stroke prevention. 1, 2

Step 7: Consider Cost and Patient Preference

• Thiazide-type diuretics are more affordable than other agents and remain underused despite proven efficacy. 3
• Single-pill fixed-dose combinations markedly improve adherence and should be strongly preferred over separate pills. 1
• Discuss benefits and harms of specific BP targets with the patient, especially in older adults. 3

Critical Pitfalls to Avoid

• Do not delay combination therapy in patients with stage 2 hypertension or BP ≥20/10 mmHg above target. 1, 2
• Do not use beta-blockers as initial therapy for uncomplicated hypertension; they are less effective than thiazides or CCBs for stroke prevention. 1, 2
• Verify medication adherence before labeling treatment failure; non-adherence is the most common cause of apparent resistant hypertension. 1
• Confirm true hypertension with home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg before escalating therapy. 1
• Screen for secondary hypertension when BP ≥180/110 mmHg or when resistant to triple-drug therapy. 1
• Never combine ACEI with ARB (dual renin-angiotensin system blockade raises risk of hyperkalemia and acute kidney injury). 1, 2

Monitoring and Follow-Up

• Reassess BP 2-4 weeks after initiating or adjusting therapy. 1, 2
• Aim to reach target BP within 3 months of therapy initiation or modification. 1, 2
• Check serum potassium and creatinine at baseline, 2-4 weeks after starting or dose change, and annually if stable. 2
• Lifestyle interventions (sodium restriction <2 g/day, DASH diet, weight loss, regular exercise, limited alcohol) can lower systolic BP by 10-20 mmHg. 1