What is the first-line medication for Hypertension (Htn)?

First-Line Blood Pressure Medication for Hypertension

Thiazide diuretics, especially chlorthalidone, are the optimal first-line medication for hypertension treatment based on the strongest evidence for preventing cardiovascular disease outcomes. 1

Initial Medication Selection Algorithm

First-line options (in order of preference):

• Thiazide or thiazide-like diuretics (especially chlorthalidone)

  • Strongest evidence for prevention of cardiovascular events 1, 2
  • Superior to other agents in landmark trials 2
  • Particularly effective for preventing heart failure 1

• Calcium Channel Blockers (CCBs)

  • Effective alternative when thiazides cannot be used 1
  • Particularly effective for stroke prevention 1
  • Preferred in Black patients (along with thiazide diuretics) 1

• ACE Inhibitors or ARBs

  • Effective for BP reduction 1
  • Particularly beneficial in patients with specific comorbidities (diabetes, CKD, heart failure) 1
  • ACE inhibitors may be less effective in Black patients 1

Special Population Considerations:

• Black patients: Thiazide diuretics or CCBs are preferred first-line agents 1

• Patients with albuminuria: ACE inhibitors or ARBs should be initial treatment 1

• Patients with established coronary artery disease: ACE inhibitors or ARBs are recommended first-line 1

• Patients with heart failure: ACE inhibitors, ARBs, or beta-blockers are preferred 1

Monotherapy vs. Combination Therapy

• For Stage 1 hypertension (130-139/80-89 mmHg): Single-agent therapy is reasonable 1

• For Stage 2 hypertension (≥140/90 mmHg): Initial treatment with two antihypertensive medications is recommended 1

• For BP ≥160/100 mmHg or >20/10 mmHg above target: Start with two-drug combination 1

Evidence Supporting Thiazide Diuretics as First-Line

Thiazide diuretics, particularly chlorthalidone, have the strongest evidence supporting their use as first-line therapy:

• In the largest head-to-head comparison of first-step drug therapy (ALLHAT trial), chlorthalidone was superior to amlodipine (CCB) and lisinopril (ACE inhibitor) in preventing heart failure 1

• Chlorthalidone was also superior to lisinopril in preventing stroke in Black patients 2

• Diuretics have been shown to be more effective than beta-blockers and calcium channel blockers for preventing heart failure 1

• Low-dose diuretics have been shown to be more effective as first-line treatment for preventing heart failure compared to ACE inhibitors, beta-blockers, or calcium channel blockers 1

Common Pitfalls and Caveats

• Beta-blockers are not recommended as first-line therapy unless there are specific indications (prior MI, active angina, heart failure with reduced ejection fraction) 1

• Alpha-blockers should not be used as first-line therapy due to inferior cardiovascular protection compared to other agents 1

• Medication selection should consider comorbidities - diabetes, CKD, heart failure, and coronary artery disease may influence the choice of agent 1

• Thiazide diuretics can cause metabolic effects including hyperglycemia and diabetes, though this does not reduce their efficacy in preventing cardiovascular events 2

• Single-pill combinations may improve medication adherence but may contain lower-than-optimal doses of the thiazide component 1

• ACE inhibitors and ARBs should never be used in combination due to increased risk of adverse effects without additional benefit 1