What is the first line treatment for hypertension?

First-Line Treatment for Hypertension

For most patients with hypertension, first-line treatment should include a thiazide diuretic, calcium channel blocker (CCB), ACE inhibitor, or angiotensin receptor blocker (ARB), with combination therapy recommended for those with stage 2 hypertension. 1

Initial Medication Selection

First-Line Agents

• Thiazide or thiazide-like diuretics (especially chlorthalidone)
• ACE inhibitors
• ARBs
• Dihydropyridine calcium channel blockers (CCBs)

These four drug classes have demonstrated the most effective reduction in blood pressure and cardiovascular events in high-quality randomized controlled trials 1.

Special Population Considerations

• For Black patients: Thiazide diuretics or CCBs are more effective as initial therapy 1
• For patients with albuminuria: ACE inhibitor or ARB is recommended 1
• For patients with coronary artery disease: ACE inhibitor or ARB is preferred 1

Monotherapy vs. Combination Therapy

Stage 1 Hypertension (BP 130-139/80-89 mmHg)

• Start with a single antihypertensive drug
• Titrate dose and add sequential agents as needed to achieve BP target 1

Stage 2 Hypertension (BP ≥140/90 mmHg)

• Initiate treatment with two first-line agents of different classes
• Can be given as separate agents or fixed-dose combination
• Particularly important if BP is >20/10 mmHg above target 1

Evidence Supporting Specific First-Line Agents

Thiazide Diuretics

• Strongest evidence supports chlorthalidone (a thiazide-like diuretic)
• More effective than CCBs for preventing heart failure 1
• Chlorthalidone has been shown to be superior to amlodipine (CCB) and lisinopril (ACE inhibitor) in preventing heart failure 1
• Starting dose for chlorthalidone is typically 12.5-25 mg daily 2

ACE Inhibitors/ARBs

• Particularly beneficial in patients with:
  • Diabetes
  • Chronic kidney disease
  • Albuminuria
  • Left ventricular dysfunction 1
• ARBs may be better tolerated than ACE inhibitors in Black patients (less cough and angioedema) 1

Calcium Channel Blockers

• As effective as diuretics for reducing all cardiovascular events except heart failure 1
• Good alternative when thiazide diuretics are not tolerated 1

Treatment Algorithm

1. Assess BP and cardiovascular risk

2. Choose initial therapy based on:

   • BP level (stage 1 vs. stage 2)
   • Race (Black vs. non-Black)
   • Presence of comorbidities (diabetes, CKD, heart failure)
   • Albuminuria status

3. For stage 1 hypertension:

   • Start with single agent (thiazide diuretic, ACE inhibitor, ARB, or CCB)
   • For non-Black patients: ACE inhibitor or ARB often preferred
   • For Black patients: Thiazide diuretic or CCB preferred

4. For stage 2 hypertension:

   • Start with two-drug combination
   • Preferred combinations: RAS blocker (ACE inhibitor or ARB) + dihydropyridine CCB or diuretic 1
   • Fixed-dose single-pill combinations recommended to improve adherence 1

Common Pitfalls and Caveats

1. Avoid combining ACE inhibitors with ARBs - This combination increases adverse effects without additional benefit 1

2. Beta-blockers are not recommended as first-line unless there are compelling indications such as:

   • Angina
   • Post-myocardial infarction
   • Heart failure with reduced ejection fraction 1
   • Beta-blockers have been shown to be less effective than diuretics for prevention of stroke and cardiovascular events 1

3. Chlorthalidone vs. Hydrochlorothiazide:

   • Chlorthalidone has stronger evidence for cardiovascular outcomes 3
   • At equivalent doses, chlorthalidone provides greater 24-hour blood pressure reduction than hydrochlorothiazide 3

4. Medication timing:

   • Current evidence does not show benefit of specific timing of BP medication administration
   • Medications should be taken at the most convenient time to improve adherence 1

5. Elderly patients:

   • Consider starting at lower doses and titrating more gradually 4
   • Avoid excessive lowering of diastolic blood pressure below 70-75 mmHg in elderly patients with coronary heart disease 4

Remember that the goal of treatment should be reduction in blood pressure to target levels (generally <130/80 mmHg) to reduce cardiovascular morbidity and mortality. Most patients will ultimately require multiple medications to achieve adequate blood pressure control.