What is the initial pharmacological approach for managing Hypertension (Htn)?

Initial Pharmacological Management of Hypertension

For most patients with confirmed hypertension (BP ≥140/90 mmHg), initiate treatment with combination therapy using two first-line antihypertensive medications, preferably as a single-pill combination of a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic. 1

Blood Pressure Thresholds for Starting Medication

• Start pharmacological treatment immediately for all patients with confirmed hypertension (BP ≥140/90 mmHg) regardless of cardiovascular disease status 1, 2
• For patients with existing cardiovascular disease and BP 130-139/70-89 mmHg, initiate treatment due to their elevated risk 2
• For patients without cardiovascular disease but with high cardiovascular risk, diabetes, or chronic kidney disease and BP 130-139 mmHg, strongly consider treatment 2, 3

First-Line Medication Classes

The four evidence-based first-line drug classes are 1, 2:

• ACE inhibitors (e.g., lisinopril 10 mg daily initially) 4
• Angiotensin receptor blockers (ARBs)
• Dihydropyridine calcium channel blockers (long-acting)
• Thiazide or thiazide-like diuretics (chlorthalidone, indapamide, hydrochlorothiazide)

Combination Therapy vs. Monotherapy

Combination therapy is superior to monotherapy for most patients: 1

• For BP ≥160/100 mmHg: Always start with two-drug combination 3
• For BP 140-159/90-99 mmHg: Combination therapy is preferred, though monotherapy may be considered in select cases 1, 2
• Exceptions to combination therapy: Patients aged ≥85 years, symptomatic orthostatic hypotension, moderate-to-severe frailty, or elevated BP (120-139/70-89 mmHg) with specific indications 1

Preferred Two-Drug Combinations

Use these evidence-based combinations 1, 3:

• RAS blocker (ACE inhibitor or ARB) + dihydropyridine calcium channel blocker
• RAS blocker (ACE inhibitor or ARB) + thiazide/thiazide-like diuretic
• Strongly prefer single-pill combinations over separate pills to improve adherence 1, 3

Race-Specific Considerations

• In Black patients without chronic kidney disease: Initiate with thiazide diuretic or calcium channel blocker, as these are more effective than ACE inhibitors or ARBs as monotherapy 1, 3
• Black patients may still receive RAS blockers as part of combination therapy 3

Comorbidity-Specific Selection

Chronic kidney disease with albuminuria: 2, 3

• ACE inhibitor or ARB is mandatory as part of the regimen
• Does not need to be the initial agent if BP controlled with single drug without proteinuria 1

Diabetes with established coronary artery disease: 2

• ACE inhibitor or ARB as first-line therapy

Heart failure with reduced ejection fraction: 1

• Beta-blocker combined with ACE inhibitor/ARB and diuretic

Post-myocardial infarction or angina: 1

• Beta-blocker combined with other first-line agents

Escalation Strategy

If BP not controlled with two-drug combination: 1

• Escalate to three-drug combination: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic
• Preferably as single-pill combination

If BP not controlled with three-drug combination (resistant hypertension): 1, 3

• Add spironolactone at low dose as fourth agent
• If spironolactone not tolerated: Consider eplerenone, beta-blocker (if not already prescribed), alpha-blocker, or centrally acting agent

Critical Contraindications

Never combine: 1, 2

• ACE inhibitor + ARB (increased risk of hyperkalemia, syncope, acute kidney injury)
• ACE inhibitor or ARB + direct renin inhibitor

Target Blood Pressure Goals

• Most patients without comorbidities: <140/90 mmHg 2, 5
• Patients with cardiovascular disease: <130/80 mmHg 2, 6
• High-risk patients (diabetes, chronic kidney disease, high cardiovascular risk): <130/80 mmHg 2, 3
• Elderly patients (>60 years): <150/90 mmHg per some guidelines, though <140/90 mmHg remains reasonable if tolerated 1

Monitoring and Follow-Up

• Monthly visits after initiation or medication changes until BP target achieved 2, 3
• Achieve BP control within 3 months to maintain patient confidence and adherence 1
• Monitor serum creatinine/eGFR and potassium at least annually when using ACE inhibitors, ARBs, or diuretics 2, 3
• Once controlled, follow-up every 3-5 months 2

Timing of Medication Administration

• Take medications at the most convenient time of day to improve adherence 1
• No evidence supports specific diurnal timing for cardiovascular outcomes 1
• Encourage same time each day in consistent setting 1

Common Pitfalls to Avoid

• Do not use sequential monotherapy as default approach - this delays BP control and frustrates patients, especially those at high cardiovascular risk 3
• Do not delay treatment to complete cardiovascular risk assessment - this can be done after initiating therapy 2
• Do not discontinue medications if BP falls below target without adverse effects - continue the regimen 1
• Do not use immediate-release nifedipine for hypertension management 7, 8
• Address medication adherence proactively - poor compliance is the most common cause of resistant hypertension 3