What is the preferred treatment for hypertension?

Preferred Treatment for Hypertension

For most patients with confirmed hypertension (BP ≥140/90 mmHg), initial treatment should be combination therapy with a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic, preferably as a single-pill combination. 1

Treatment Initiation Thresholds

• Pharmacological therapy should be initiated when BP ≥140/90 mmHg in most patients, combined with lifestyle modifications 1
• For high-risk patients (established CVD, diabetes, chronic kidney disease, or ≥10% 10-year ASCVD risk), initiate pharmacological therapy at BP ≥130/80 mmHg 1, 2
• Stage 2 hypertension (BP ≥160/100 mmHg) requires immediate initiation of two-drug combination therapy from different classes 1
• For elevated BP (120-139/70-89 mmHg) with low CVD risk (<10%), lifestyle modifications alone for 3-6 months before considering medication 1, 2

First-Line Pharmacological Agents

The four evidence-based first-line medication classes are equally effective for most patients 1, 2:

1. Thiazide or thiazide-like diuretics (chlorthalidone 12.5-25 mg daily preferred over hydrochlorothiazide due to longer half-life and proven CVD reduction) 1
2. ACE inhibitors (e.g., lisinopril 10-40 mg daily, enalapril 5-40 mg daily) 1
3. Angiotensin receptor blockers (ARBs) (e.g., losartan 50-100 mg daily, candesartan 8-32 mg daily) 1
4. Long-acting dihydropyridine calcium channel blockers (e.g., amlodipine 5-10 mg daily) 1

Preferred Combination Therapy Approach

The 2024 ESC guidelines represent the most current evidence and recommend combination therapy as initial treatment for most patients, departing from older step-wise approaches 1:

• Preferred two-drug combinations: RAS blocker (ACE inhibitor or ARB) + dihydropyridine CCB OR RAS blocker + thiazide/thiazide-like diuretic 1, 2
• Fixed-dose single-pill combinations are strongly recommended to improve adherence 1
• If BP remains uncontrolled on two drugs, escalate to three-drug combination: RAS blocker + CCB + thiazide/thiazide-like diuretic 1

Exceptions to combination therapy include patients ≥85 years, symptomatic orthostatic hypotension, moderate-to-severe frailty, or elevated BP (not hypertension) with specific indications 1

Special Population Considerations

Black Patients

• Calcium channel blockers or thiazide diuretics are more effective than ACE inhibitors or ARBs as monotherapy 2, 3
• However, combination therapy with RAS blocker + CCB or diuretic remains appropriate 2

Patients with Albuminuria (UACR ≥30 mg/g)

• ACE inhibitor or ARB is mandatory as first-line therapy because these agents reduce proteinuria and slow kidney disease progression beyond BP lowering alone 1, 2, 4
• This takes precedence over other considerations 2

Patients with Diabetes

• ACE inhibitor or ARB is first-line therapy, especially with albuminuria 1, 2
• Target BP <130/80 mmHg 1, 2
• For diabetic patients without albuminuria, thiazide-like diuretics or dihydropyridine CCBs are also appropriate 1

Patients with Coronary Artery Disease

• ACE inhibitor or ARB should be selected as first-line therapy 2, 4
• Beta-blockers are recommended when combined with other BP-lowering classes for compelling indications (post-MI, angina, heart failure, heart rate control) 1

Patients with Chronic Kidney Disease

• ACE inhibitors or ARBs are first-line drugs because they reduce albuminuria and slow CKD progression 1, 2, 4
• Monitor serum creatinine and potassium closely 1, 2, 4

Women of Childbearing Potential

• ACE inhibitors and ARBs are absolutely contraindicated in pregnancy and should be avoided in fertile women 5
• Calcium channel blockers (amlodipine, nifedipine extended-release) are the preferred first-line choice 5
• Methyldopa and labetalol are acceptable alternatives 5

Elderly Patients (≥60-65 years)

• Target systolic BP <130 mmHg if well tolerated 1, 2
• For patients ≥60 years, target systolic BP <150 mmHg is acceptable if intensive targets are poorly tolerated 1
• Continue BP-lowering treatment lifelong, even beyond age 85, if well tolerated 1

Patients with History of Stroke/TIA

• Consider intensifying treatment to achieve systolic BP <140 mmHg to reduce recurrent stroke risk 1
• ACE inhibitor plus diuretic combination is preferred 6

Blood Pressure Targets

The most recent 2024 ESC guidelines recommend the most aggressive targets 1:

• Target systolic BP 120-129 mmHg in most adults if well tolerated 1
• If poorly tolerated, apply the "as low as reasonably achievable" (ALARA) principle 1
• Target <130/80 mmHg for patients with established CVD 1, 2
• Target <130/80 mmHg for high-risk patients (diabetes, CKD, high CVD risk) 1, 2
• Target <140/90 mmHg minimum for all patients without comorbidities 1

The 2017 ACC/AHA guidelines similarly recommend <130/80 mmHg for most adults <65 years 1, 2, while older guidelines (ACP/AAFP 2017) suggest <150/90 mmHg for adults ≥60 years may be acceptable 1. Given the most recent and highest quality evidence from the 2024 ESC guidelines, targeting 120-129 mmHg systolic is preferred when tolerated 1.

Essential Lifestyle Modifications

Lifestyle modifications should be implemented for all patients with BP >120/80 mmHg 2, 3:

• Dietary sodium restriction to <2,300 mg/day (approximately 100 mmol/day), ideally 65-100 mmol/day for hypertensives 1, 4, 6
• Weight loss if overweight (target BMI 20-25 kg/m², waist <94 cm men/<80 cm women) 1, 4, 3
• Adopt DASH or Mediterranean dietary pattern emphasizing fruits, vegetables, low-fat dairy, whole grains, reduced saturated fat 1, 4, 3
• Increase dietary potassium intake 1, 3
• Aerobic exercise ≥150 minutes/week of moderate intensity plus resistance training 2-3 times/week 1, 4, 3
• Alcohol limitation to <100 g/week (preferably avoid completely) 1, 4, 3
• Complete tobacco smoking cessation 1, 4, 3
• Restrict free sugar consumption, especially sugar-sweetened beverages 1, 4

A 10 mmHg reduction in systolic BP decreases cardiovascular events by 20-30%, highlighting the critical importance of achieving BP control 3.

Critical Monitoring Requirements

• Monitor serum creatinine and potassium within 7-14 days after initiating or changing doses of ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1, 2, 4
• Follow-up monthly after medication initiation or dose changes until BP target achieved 1
• Once controlled, follow-up every 3-5 months 1
• Goal: achieve BP target within 3 months 2

Absolute Contraindications and Critical Caveats

• NEVER combine ACE inhibitor + ARB + renin inhibitor—this is potentially harmful without additional benefit and increases risk of hyperkalemia and acute kidney injury 1, 2, 4
• NEVER combine two RAS blockers (ACE inhibitor + ARB) 1, 4
• ACE inhibitors and ARBs are absolutely contraindicated in pregnancy and should be avoided in sexually active women of childbearing potential not using reliable contraception 2, 5
• Beta-blockers are not first-line monotherapy except when compelling indications exist (post-MI, angina, heart failure, heart rate control) 1, 2
• Renal denervation is not recommended as first-line therapy due to lack of adequately powered outcomes trials 1

Treatment Algorithm Summary

1. Assess BP level and cardiovascular risk
2. Initiate lifestyle modifications for all patients with BP >120/80 mmHg 1, 2, 4
3. For BP ≥140/90 mmHg (or ≥130/80 mmHg if high-risk): Start combination therapy immediately with RAS blocker + CCB or diuretic, preferably as single-pill combination 1, 2
4. Modify first-line choice based on compelling indications: albuminuria (ACE-I/ARB mandatory), black race (CCB or diuretic preferred), fertile women (CCB preferred), CAD (ACE-I/ARB preferred) 2, 5, 4
5. If uncontrolled on two drugs: Add third agent (typically completing the triad of RAS blocker + CCB + thiazide-like diuretic) 1
6. If uncontrolled on three drugs: Consider mineralocorticoid receptor antagonist (spironolactone or eplerenone) with close monitoring of potassium 1
7. Target systolic BP 120-129 mmHg if tolerated, minimum <140/90 mmHg 1

Common pitfall: Only 44% of US adults with hypertension have BP controlled to <140/90 mmHg 3, often due to clinical inertia in intensifying therapy. Aggressive, prompt escalation to combination therapy and titration to target is essential to reduce cardiovascular morbidity and mortality 1, 3.