What are the recommended first-line medications for Hypertension?

First-Line Medications for Hypertension

First-line medications for hypertension include thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers, with thiazide diuretics having the strongest evidence for cardiovascular outcomes in uncomplicated hypertension. 1

Recommended First-Line Agents

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend the following as first-line agents for hypertension:

• Thiazide or thiazide-like diuretics (preferably chlorthalidone)
• ACE inhibitors (e.g., lisinopril)
• ARBs (e.g., losartan)
• Calcium channel blockers (CCBs, dihydropyridine type)

Evidence Supporting Each Class

1. Thiazide Diuretics:

   • Have the strongest evidence for cardiovascular outcomes in uncomplicated hypertension 1
   • Chlorthalidone is preferred over hydrochlorothiazide due to better efficacy and cardiovascular outcomes 1, 2
   • Reduce all-cause mortality compared to placebo 2

2. ACE Inhibitors:

   • Reduce all-cause mortality compared to placebo 2
   • Indicated for hypertension to lower blood pressure and reduce fatal and non-fatal cardiovascular events 3
   • Less effective than thiazide diuretics in preventing stroke and less effective in Black patients 1

3. ARBs:

   • Similar efficacy to ACE inhibitors but with fewer side effects (particularly cough) 4
   • Effective across different patient populations 1

4. Calcium Channel Blockers:

   • Effective across demographic groups
   • Less effective than thiazide diuretics in preventing heart failure 1

Patient-Specific Considerations

Blood Pressure Severity

• BP 140-159/90-99 mmHg: May begin with a single drug
• BP ≥160/100 mmHg: Initial combination therapy with two drugs from different classes is recommended 5, 1

Comorbidities

• Diabetes: ACE inhibitors or ARBs are preferred first-line agents 5, 1
• Chronic kidney disease with albuminuria: ACE inhibitors or ARBs are recommended 5
• Coronary artery disease: ACE inhibitors or ARBs are recommended first-line 5
• Heart failure: ACE inhibitors, ARBs, or beta-blockers are preferred 1

Demographic Considerations

• Black patients: Thiazide diuretics or CCBs are more effective as initial therapy 1
• Elderly patients (≥65 years): Same medications but may require more careful dose titration 1

Combination Therapy

• Multiple-drug therapy is often required to achieve blood pressure targets 5
• For Stage 2 hypertension (≥160/100 mmHg), initiate with two drugs from different classes 1
• Effective combinations include:
  • Thiazide diuretic + ACE inhibitor/ARB
  • Thiazide diuretic + CCB
  • ACE inhibitor/ARB + CCB

Important Cautions

• Do not combine:

  • ACE inhibitors with ARBs
  • ACE inhibitors or ARBs with direct renin inhibitors
  • These combinations increase adverse effects without additional benefit 5, 1

• Monitoring:

  • For patients on ACE inhibitors, ARBs, or diuretics: Check serum creatinine/eGFR and potassium at least annually 5
  • For diuretics: Evaluate renal function and electrolytes 2-4 weeks after initiation 1

Lifestyle Modifications

Always incorporate lifestyle modifications alongside medication:

• Weight loss (5-20 mmHg reduction per 10 kg lost)
• DASH diet (8-14 mmHg reduction)
• Sodium restriction (2-8 mmHg reduction)
• Physical activity (4-9 mmHg reduction)
• Moderate alcohol consumption (2-4 mmHg reduction) 1, 6

Follow-up and Monitoring

• Follow up in 1 month for Stage 2 hypertension
• Monitor every 3-6 months after BP control is achieved
• Assess medication adherence, side effects, and laboratory parameters 1

Common Pitfalls to Avoid

1. Inappropriate drug combinations (e.g., ACE inhibitor + ARB)
2. Overlooking lifestyle modifications
3. Therapeutic inertia (not intensifying treatment when BP remains uncontrolled)
4. Inaccurate BP measurement leading to over or under-treatment 1