First-Line Treatment for Hypertension
First-line antihypertensive drug therapy should include thiazide diuretics, calcium channel blockers (CCBs), or ACE inhibitors/ARBs, with thiazide diuretics (especially chlorthalidone) often being the preferred initial choice due to their proven efficacy in reducing cardiovascular events. 1
Initial Treatment Selection
Based on Hypertension Severity:
- For Stage 1 hypertension (BP 130-159/80-99 mmHg): Initiation with a single antihypertensive drug is reasonable, with dosage titration and sequential addition of other agents to achieve BP target 1
- For Stage 2 hypertension (BP ≥160/100 mmHg) or BP >20/10 mmHg above target: Initiation with 2 first-line agents of different classes is recommended, either as separate agents or in a fixed-dose combination 1
First-Line Drug Classes:
- Thiazide diuretics (especially chlorthalidone)
- ACE inhibitors
- ARBs
- Calcium channel blockers (CCBs)
These classes have all demonstrated efficacy in reducing cardiovascular disease events compared to placebo 1, 2
Special Population Considerations
Race-Specific Recommendations:
- For Black patients with hypertension (without heart failure or chronic kidney disease): Initial treatment should include a thiazide diuretic or CCB 1
- ACE inhibitors are less effective than thiazide diuretics and CCBs in Black patients for prevention of stroke and heart failure 1
Comorbidity-Based Selection:
- 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 patients with diabetes and established coronary artery disease: ACE inhibitors or ARBs are recommended as first-line therapy 1
Evidence for Thiazide Diuretics
Thiazide diuretics have particularly strong evidence supporting their use as first-line therapy:
- Diuretics, especially the long-acting thiazide-type agent chlorthalidone, may provide an optimal choice for first-step drug therapy 1
- In systematic reviews and network meta-analyses, diuretics were significantly better than CCBs for prevention of heart failure 1
- Chlorthalidone has been shown to be superior to the ACE inhibitor lisinopril in preventing stroke and superior to the CCB amlodipine in preventing heart failure 1, 3
Comparative Effectiveness of Thiazide Diuretics
- Chlorthalidone has been extensively studied in landmark trials with over 50,000 patients and demonstrated efficacy in reducing cardiovascular events 3
- Within recommended doses, chlorthalidone appears more effective in lowering systolic blood pressure than hydrochlorothiazide, as evidenced by 24-hour ambulatory blood pressure monitoring 4
- However, recent large observational studies suggest chlorthalidone may have similar cardiovascular benefits to hydrochlorothiazide but with higher risk of electrolyte abnormalities and renal issues 5
Practical Approach to First-Line Treatment
- Assess hypertension severity and cardiovascular risk factors
- Consider patient demographics (race, age) and comorbidities
- For most patients without specific comorbidities:
- For patients with specific indications:
Common Pitfalls and Caveats
- Beta blockers are not recommended as first-line therapy for uncomplicated hypertension as they are less effective than other agents, especially for stroke prevention in older adults 1
- Combination of ACE inhibitors and ARBs is not recommended due to lack of added benefit and increased adverse events 1
- When using ACE inhibitors, ARBs, or diuretics, monitor serum creatinine, eGFR, and potassium levels within 7-14 days after initiation and at least annually 1
- Alpha blockers are not recommended as first-line therapy as they are less effective for prevention of cardiovascular disease than other first-step agents 1