What is the complete management of Hypertension (HTN) with drug classes, doses, indications, and contraindications?

Complete Hypertension Management

Blood Pressure Thresholds for Initiating Treatment

Start pharmacological treatment immediately for all patients with confirmed BP ≥140/90 mmHg, and for those with BP 130-139/80-89 mmHg who have existing cardiovascular disease. 1

• For patients with BP ≥140/90 mmHg: Initiate drug therapy regardless of cardiovascular risk 1
• For patients with BP 130-139/80-89 mmHg AND existing CVD: Start treatment immediately 1
• For patients with BP 130-139/80-89 mmHg AND high CVD risk, diabetes, or chronic kidney disease: Consider treatment (conditional recommendation) 1
• For patients with BP 120-139/70-89 mmHg without high-risk features: Implement lifestyle modifications for 3 months before considering medication 1, 2

First-Line Drug Classes and Dosing

Initiate combination therapy with two drugs from different classes for most patients with confirmed hypertension (BP ≥140/90 mmHg), preferably as a single-pill combination. 1

The Four Major First-Line Drug Classes:

1. ACE Inhibitors 1

• Lisinopril: Start 10 mg once daily, titrate to 20-40 mg daily 2, 3
• Enalapril: 5-40 mg daily in 1-2 divided doses 4
• Bioavailability ~25%, peak effect 6-8 hours, duration 24 hours 5

2. Angiotensin Receptor Blockers (ARBs) 1

• Losartan: Start 50 mg once daily, titrate to 50-100 mg daily 2, 6
• Candesartan: 8-32 mg once daily 4

3. Long-Acting Dihydropyridine Calcium Channel Blockers 1

• Amlodipine: Start 5 mg once daily, titrate to 5-10 mg daily 2, 7
• Nifedipine (extended-release): 30-90 mg once daily 4

4. Thiazide/Thiazide-Like Diuretics 1

• Chlorthalidone: 12.5-25 mg once daily (preferred thiazide-like) 4, 8
• Hydrochlorothiazide: 12.5-50 mg once daily 4
• Indapamide: 1.25-2.5 mg once daily 1

Treatment Algorithm

Step 1: Initial Therapy

For most patients with hypertension (BP ≥140/90 mmHg): Start with low-dose two-drug combination 1

Preferred combinations: 1

• ACE inhibitor or ARB + Calcium channel blocker
• ACE inhibitor or ARB + Thiazide/thiazide-like diuretic
• Calcium channel blocker + Thiazide/thiazide-like diuretic

Exception - Start with monotherapy for: 1, 2

• Patients ≥85 years old
• Elevated BP (120-139/70-89 mmHg) with compelling indication
• Moderate-to-severe frailty
• Symptomatic orthostatic hypotension

Step 2: If BP Not Controlled After 4 Weeks

Escalate to triple-drug combination: RAS blocker (ACE inhibitor or ARB) + Calcium channel blocker + Thiazide/thiazide-like diuretic, preferably as single-pill combination 1

Step 3: Resistant Hypertension (Uncontrolled on Triple Therapy)

Add spironolactone 25-50 mg once daily as fourth-line agent 1, 2

If spironolactone not tolerated, consider: 1

• Eplerenone 50-200 mg daily (may require twice-daily dosing)
• Vasodilating beta-blocker (labetalol, carvedilol, or nebivolol) if not already indicated

Fifth-line options (only after above fail): 1

• Amiloride or triamterene
• Alpha-blockers (doxazosin)
• Centrally acting agents (clonidine)
• Hydralazine
• Minoxidil (last resort due to significant side effects)

Blood Pressure Targets

Target systolic BP 120-129 mmHg for most adults if well tolerated; otherwise use "as low as reasonably achievable" (ALARA) principle 1

• General hypertension without comorbidities: <140/90 mmHg 1
• Known CVD: <130 mmHg systolic (strong recommendation) 1
• High CVD risk, diabetes, or chronic kidney disease: <130 mmHg systolic (conditional recommendation) 1
• Most adults (2024 ESC): 120-129 mmHg systolic if tolerated 1
• Elderly ≥65 years: Individualize based on frailty; 130-139 mmHg systolic if intensive target not tolerated 2

Important caveat: Avoid diastolic BP <60 mmHg in high-risk patients with treated systolic BP <130 mmHg, as this may increase cardiovascular events; optimal diastolic range appears to be 70-80 mmHg 1

Compelling Indications for Specific Drug Classes

ACE Inhibitors or ARBs (First Choice): 1, 2, 3

• Heart failure (any ejection fraction)
• Post-myocardial infarction
• Chronic kidney disease with albuminuria (ACR ≥300 mg/g)
• Type 1 or Type 2 diabetic nephropathy
• Coronary artery disease
• Secondary stroke prevention

Calcium Channel Blockers (First Choice): 2

• Black patients (more effective than ACE inhibitors/ARBs as monotherapy)
• Elderly patients
• Isolated systolic hypertension

Thiazide/Thiazide-Like Diuretics (First Choice): 2, 4

• Black patients
• Elderly patients
• Osteoporosis (reduces calcium excretion)

Beta-Blockers (Add-On, Not First-Line Unless Indicated): 1, 2

• Post-myocardial infarction
• Heart failure with reduced ejection fraction
• Angina pectoris
• Atrial fibrillation requiring rate control
• Not recommended as first-line for uncomplicated hypertension 1, 2

Absolute Contraindications

ACE Inhibitors: 1, 3

• Pregnancy (teratogenic)
• Bilateral renal artery stenosis or stenosis in solitary kidney
• History of angioedema with ACE inhibitors
• Hereditary or idiopathic angioedema

ARBs: 1, 6

• Pregnancy (teratogenic)
• Bilateral renal artery stenosis

Calcium Channel Blockers (Dihydropyridines): 1

• Severe aortic stenosis (relative)
• Unstable angina without beta-blocker

Thiazide Diuretics: 1

• Gout (relative contraindication; may precipitate attacks)
• Severe hyponatremia or hypokalemia

Beta-Blockers: 1

• Severe asthma or COPD with bronchospasm
• High-degree AV block (without pacemaker)
• Severe bradycardia

Spironolactone/MRAs: 1

• Hyperkalemia (K+ >5.0 mEq/L)
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Addison's disease

Important Contraindicated Combinations

Never combine ACE inhibitor with ARB - increases adverse effects (hyperkalemia, acute kidney injury, hypotension) without additional benefit 1, 2

Avoid thiazide diuretic + beta-blocker in patients with metabolic syndrome or high diabetes risk - synergistic dysmetabolic effects including incident diabetes 1

Race/Ethnicity Considerations

For Black patients: Initiate therapy with calcium channel blocker or thiazide-like diuretic rather than ACE inhibitor or ARB 2, 3, 7

• ACE inhibitors and ARBs have reduced BP-lowering efficacy as monotherapy in Black patients 3, 7
• Losartan does NOT reduce stroke risk in Black patients with left ventricular hypertrophy (unlike non-Black patients) 6
• Combination therapy overcomes this differential response 2

Monitoring and Follow-Up

Follow up monthly after initiating or changing medications until BP target achieved 1

Once controlled, follow up every 3-5 months 1

Laboratory monitoring before starting treatment (if does not delay therapy): 1

• Serum creatinine and eGFR
• Serum potassium
• Fasting glucose or HbA1c
• Lipid panel
• Urinalysis for proteinuria

During treatment with ACE inhibitors/ARBs or diuretics: 1

• Recheck creatinine and potassium within 1-2 weeks of initiation or dose increase
• Monitor for hyperkalemia with ACE inhibitors/ARBs (especially if combined with spironolactone)
• Monitor for hypokalemia with thiazide diuretics

Lifestyle Modifications (Adjunctive to All Pharmacotherapy)

Implement these measures in all patients, as they enhance drug efficacy and may reduce medication requirements: 1, 4

• Sodium restriction: <2 g/day (5 g salt) 1
• Weight loss: Target BMI <25 kg/m² 1
• DASH diet: High in fruits, vegetables, low-fat dairy, reduced saturated fat 4
• Physical activity: 150 minutes/week moderate-intensity aerobic exercise 1
• Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 1
• Smoking cessation: Mandatory for CVD risk reduction 1
• Potassium supplementation: 3.5-5 g/day (if no contraindication) 4

Common Pitfalls to Avoid

Do not delay treatment initiation for extensive cardiovascular risk assessment - start treatment first, assess risk later if feasible 1

Do not use immediate-release nifedipine for hypertensive urgencies - causes unpredictable precipitous BP drops 9

Do not use beta-blockers as first-line monotherapy for uncomplicated hypertension - less effective at preventing stroke compared to other first-line agents 1, 2

Do not target diastolic BP <60 mmHg in patients with treated systolic BP <130 mmHg - associated with increased cardiovascular events 1

Do not use hydralazine or minoxidil until all other options exhausted - significant side effects including reflex tachycardia and fluid retention 1

Assess medication adherence before labeling as resistant hypertension - non-adherence is the most common cause of apparent treatment resistance 1

Hypertensive Emergencies (BP >180/120 mmHg with Acute End-Organ Damage)

Admit to ICU and use short-acting IV antihypertensives with goal to reduce BP by 20-25% in first hour 9

Preferred IV agents: 9

• Labetalol 20-80 mg IV bolus or infusion
• Nicardipine 5-15 mg/hour IV infusion
• Clevidipine 1-16 mg/hour IV infusion
• Esmolol 500-1000 mcg/kg/min IV infusion
• Fenoldopam 0.1-0.3 mcg/kg/min IV infusion

Avoid: 9

• Sodium nitroprusside (cyanide toxicity risk; use only if no alternatives)
• Immediate-release nifedipine
• Hydralazine (unpredictable response)

Single-Pill Combinations to Improve Adherence

Strongly prefer single-pill combinations over separate pills when using combination therapy 1, 2

• Improves adherence and persistence 1, 2
• Simplifies regimen 1
• Multiple fixed-dose combinations available for all preferred drug class pairings 1