What is the first-line treatment for hypertension?

First-Line Treatment for Hypertension

The first-line treatment for hypertension should be a combination of a renin-angiotensin system (RAS) blocker (ACE inhibitor or ARB) with either a dihydropyridine calcium channel blocker (CCB) or a thiazide/thiazide-like diuretic for most patients with confirmed hypertension (BP ≥140/90 mmHg). 1

Initial Medication Selection

First-line drug classes:

• ACE inhibitors (e.g., lisinopril)
• ARBs (e.g., losartan)
• Dihydropyridine calcium channel blockers (e.g., amlodipine)
• Thiazide or thiazide-like diuretics (e.g., chlorthalidone, indapamide) 1, 2

Patient-specific considerations:

1. For non-Black patients:

   • Preferred initial therapy: ACE inhibitor/ARB + dihydropyridine CCB or thiazide-like diuretic 2

2. For Black patients:

   • Preferred initial therapy: ARB + dihydropyridine CCB or dihydropyridine CCB + thiazide-like diuretic 2
   • Note: ACE inhibitors are less effective than thiazide diuretics and CCBs in lowering BP and preventing stroke in Black patients 1

3. For patients with albuminuria (UACR ≥30 mg/g):

   • Initial treatment should include an ACE inhibitor or ARB to reduce risk of progressive kidney disease 1
   • For UACR ≥300 mg/g: ACE inhibitor or ARB at maximum tolerated dose is strongly recommended 1

4. For patients with diabetes and hypertension:

   • ACE inhibitor or ARB is recommended, particularly with albuminuria 1

Monotherapy vs. Combination Therapy

• For most patients with confirmed hypertension (BP ≥140/90 mmHg):

  • Combination therapy is recommended as initial treatment 1
  • Fixed-dose single-pill combinations are preferred for better adherence 1

• Exceptions where monotherapy may be considered:

  • Patients aged ≥85 years
  • Those with symptomatic orthostatic hypotension
  • Patients with moderate-to-severe frailty
  • Patients with elevated BP (systolic BP 120-139 mmHg) 1

Treatment Algorithm

1. Initial therapy:

   • Two-drug combination (RAS blocker + CCB or diuretic) for most patients 1
   • Target BP: 120-129/70-79 mmHg for most adults 1

2. If BP not controlled with two drugs:

   • Progress to three-drug combination: RAS blocker + dihydropyridine CCB + thiazide/thiazide-like diuretic 1
   • Preferably as a single-pill combination 1

3. If BP still not controlled:

   • Add spironolactone as fourth-line agent 1, 2
   • Alternative fourth-line options if spironolactone not tolerated: eplerenone, beta-blocker, centrally acting agent, or alpha-blocker 1

Important Considerations

• Diuretic selection: Chlorthalidone and indapamide (thiazide-like diuretics) are preferred over hydrochlorothiazide due to superior efficacy and longer duration of action 3, 4

• Monitoring: For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine/eGFR and potassium levels at least annually 1

• Contraindications: Combining two RAS blockers (ACE inhibitor and ARB) is not recommended due to increased risk of hyperkalemia and acute kidney injury 1

• Lifestyle modifications: Should be recommended alongside pharmacotherapy, including:

  • Sodium restriction to approximately 2g per day
  • Regular physical activity (≥150 min/week of moderate aerobic exercise)
  • Healthy diet pattern (Mediterranean or DASH diet)
  • Weight management (target BMI 20-25 kg/m²)
  • Limited alcohol consumption 1

Pitfalls to Avoid

• Don't delay combination therapy in patients with BP significantly above target (>20/10 mmHg above goal)
• Don't use beta-blockers as first-line unless there are specific indications (angina, post-MI, heart failure) 1
• Don't combine ACE inhibitors with ARBs as this increases adverse effects without additional benefit 1
• Don't underestimate the importance of diuretics - they have demonstrated consistent reductions in cardiovascular events and are often underutilized 4
• Don't neglect medication adherence - fixed-dose combinations improve adherence and outcomes 1

The evidence strongly supports using combination therapy for most patients with hypertension, with the specific combination tailored based on patient characteristics such as race, comorbidities, and presence of albuminuria.