What is the first-line antihypertensive medication?

First-Line Antihypertensive Medications

Thiazide diuretics, particularly chlorthalidone, are the optimal first-line medications for hypertension treatment based on the strongest evidence for preventing cardiovascular disease outcomes. 1, 2

Initial Medication Selection Algorithm

For Most Patients:

• Thiazide or thiazide-like diuretics (especially chlorthalidone) have the strongest evidence for prevention of cardiovascular events and are particularly effective for preventing heart failure 1
• Calcium Channel Blockers (CCBs) are effective alternatives when thiazides cannot be used, and are particularly effective for stroke prevention 1, 2
• ACE Inhibitors or ARBs are effective for BP reduction, especially in patients with specific comorbidities (diabetes, CKD, heart failure) 1, 2

Population-Specific Considerations:

• For Black patients: Thiazide diuretics or CCBs are preferred first-line agents 1, 2
• For patients with albuminuria: ACE inhibitors or ARBs are strongly recommended as first-line therapy 2
• For patients with established coronary artery disease: ACE inhibitors or ARBs are recommended first-line 2

Evidence Supporting Thiazide Diuretics as First-Line

In the largest head-to-head comparison of first-step drug therapy for hypertension, the thiazide-type diuretic chlorthalidone was superior to the CCB amlodipine and the ACE inhibitor lisinopril in preventing heart failure, which is a BP-related outcome of increasing importance in the growing population of older persons with hypertension 1.

Additionally, ACE inhibitors were less effective than thiazide diuretics and CCBs in lowering BP and in prevention of stroke, particularly in Black patients 1. Diuretics have been shown to be more effective than beta-blockers and calcium channel blockers for preventing heart failure 2.

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, 2
• For BP ≥160/100 mmHg or >20/10 mmHg above target: Start with two-drug combination 1, 2

Medication Classes to Avoid as First-Line

• 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, 2
• Alpha-blockers should not be used as first-line therapy due to inferior cardiovascular protection compared to other agents 1, 2

Common Pitfalls and Caveats

• The combination of two RAS blockers (ACE inhibitors and ARBs) is not recommended due to increased risk of adverse effects without additional benefit 2
• Beta blockers were found to be significantly less effective than diuretics for prevention of stroke and cardiovascular events in a systematic review and network meta-analysis 1
• While ACE inhibitors and ARBs are effective antihypertensives, they are less effective in Black patients for preventing heart failure and stroke compared to CCBs and diuretics 1
• Single-pill combinations may improve medication adherence in some individuals, which is an important consideration for long-term management 2

Dosing Considerations

• For losartan (an ARB), the usual starting dose is 50 mg once daily, which can be increased to a maximum of 100 mg once daily as needed to control blood pressure 3
• For patients with possible intravascular depletion (e.g., on diuretic therapy), a lower starting dose of 25 mg is recommended 3
• For amlodipine (a CCB), dosing is typically started at lower doses and titrated upward as needed to achieve blood pressure control 4