What is the recommended initial treatment for starting antihypertensives (anti-hypertensive medications)?

How to Start Antihypertensives

For patients with blood pressure ≥160/100 mmHg, initiate treatment immediately with two antihypertensive medications from different classes, preferably as a single-pill combination; for blood pressure 130-160/80-100 mmHg, start with a single agent and titrate upward. 1

Blood Pressure Thresholds for Starting Treatment

• Start pharmacotherapy at BP ≥140/90 mmHg for all patients with confirmed hypertension 1, 2
• Start at BP 130-139/80-89 mmHg in high-risk patients with existing cardiovascular disease, diabetes, chronic kidney disease, or target organ damage 3, 2
• Lifestyle modifications should accompany all pharmacological treatment 1, 2

Monotherapy vs. Combination Therapy Decision Algorithm

Stage 2 Hypertension (BP ≥160/100 mmHg):

• Initiate with two first-line agents from different classes 1, 3
• Single-pill combinations improve adherence and should be preferred when available 1, 3
• This approach achieves blood pressure control more rapidly and effectively than sequential monotherapy 1

Stage 1 Hypertension (BP 130-159/80-99 mmHg):

• Start with a single antihypertensive agent 1, 3
• Titrate to maximum tolerated dose before adding a second agent 3
• Add a second agent if target BP not achieved within 4 weeks 3

First-Line Medication Selection by Patient Population

General Population (no specific comorbidities):

• Thiazide-type diuretics are the preferred first choice, specifically chlorthalidone over hydrochlorothiazide due to superior cardiovascular outcomes 1, 4
• Alternative first-line options include long-acting dihydropyridine calcium channel blockers (amlodipine) or ACE inhibitors (lisinopril) 1, 2
• Beta-blockers should NOT be used as first-line therapy unless specific cardiac indications exist (prior MI, active angina, heart failure with reduced ejection fraction) 1, 3

Black Patients:

• Start with either a thiazide-type diuretic OR calcium channel blocker 1, 3
• ACE inhibitors are notably less effective as monotherapy in this population for stroke and heart failure prevention 1
• If combination therapy needed, use CCB + thiazide diuretic or CCB + RAS blocker 1

Diabetes with Albuminuria (UACR ≥30 mg/g):

• ACE inhibitor or ARB is mandatory as first-line therapy to reduce progressive kidney disease 1, 3
• Add thiazide-like diuretic or calcium channel blocker as second agent if needed 1

Diabetes without Albuminuria:

• Any of the four first-line classes acceptable (thiazide diuretic, ACE inhibitor, ARB, or calcium channel blocker) 1, 3
• Thiazide-like diuretics or calcium channel blockers may be preferred given equivalent cardiovascular protection 1

Coronary Artery Disease:

• ACE inhibitors or ARBs are recommended as first-line therapy 1, 3
• Beta-blockers indicated if history of MI or active angina 1

Chronic Kidney Disease (eGFR >30 mL/min/1.73 m²):

• ACE inhibitor or ARB as first-line therapy 1, 3
• Continue these agents even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 1

Heart Failure with Reduced Ejection Fraction:

• ACE inhibitor (or ARB if intolerant) + beta-blocker + diuretic ± MRA 1
• SGLT2 inhibitors recommended for additional BP lowering and outcome improvement 1

Specific Dosing Recommendations

Starting with Monotherapy:

• Lisinopril: 10 mg once daily (5 mg if on diuretic or low systolic BP) 5
• Chlorthalidone: 12.5-15 mg once daily 4, 6
• Hydrochlorothiazide: 12.5 mg once daily (not 25 mg, which causes more metabolic side effects) 4, 6
• Amlodipine: 5 mg once daily 1

Starting with Combination Therapy:

• Preferred two-drug combinations: thiazide + ACE inhibitor, thiazide + ARB, CCB + ACE inhibitor, or CCB + ARB 1, 2
• Example: Lisinopril 10 mg + hydrochlorothiazide 12.5 mg as single-pill combination 3

Blood Pressure Targets

• General target: <130/80 mmHg for most adults 1, 3, 2
• Diabetes: <130/80 mmHg 1
• CKD with eGFR >30: systolic 120-129 mmHg if tolerated 1
• Elderly ≥65 years: <130 mmHg systolic if tolerated 3
• Home BP monitoring target: <135/85 mmHg 3

Critical Pitfalls to Avoid

Underdosing Before Adding Agents:

• Titrate first medication to maximum tolerated dose before adding a second agent 3
• Common error is adding multiple agents at subtherapeutic doses rather than optimizing initial therapy 3

Using Hydrochlorothiazide 25-50 mg:

• Higher doses cause metabolic abnormalities (hypokalemia, hyperglycemia, dyslipidemia) without additional BP benefit 4, 6
• Use 12.5 mg hydrochlorothiazide or switch to chlorthalidone 12.5-15 mg 4, 6

Beta-Blockers as First-Line:

• Less effective than diuretics and CCBs for stroke prevention (30-36% higher risk) 1, 3
• Reserve for specific cardiac indications only 1, 3

Ignoring Medication Adherence Barriers:

• Address cost and side effects proactively, as these are the most common causes of treatment failure 1, 3
• Single-pill combinations significantly improve adherence 1, 3

Inadequate Monitoring:

• Check potassium and creatinine within 7-14 days after starting ACE inhibitor or ARB 3
• Monthly follow-up until BP target achieved 3
• Reinforce home BP monitoring at every visit 3

Resistant Hypertension (BP ≥140/90 on 3 agents including diuretic)

• Add low-dose spironolactone (25 mg daily) as fourth agent 1
• If spironolactone not tolerated, use eplerenone, amiloride, or increase thiazide dose 1
• Reinforce sodium restriction (<1500 mg/day) 1, 2
• Verify medication adherence and exclude white coat hypertension before diagnosing resistant hypertension 1