First-Line Medication for Hypertension
Thiazide diuretics are the recommended first-line medication for hypertension treatment based on the strongest evidence for preventing cardiovascular disease outcomes. 1
Initial Medication Selection
The major four drug classes recommended as first-line BP-lowering medications are:
- Thiazide or thiazide-like diuretics
- ACE inhibitors
- Angiotensin receptor blockers (ARBs)
- Dihydropyridine calcium channel blockers (CCBs) 2
Thiazide or thiazide-like diuretics have the strongest evidence for prevention of cardiovascular events and are particularly effective for preventing heart failure 1, 3
Long-acting agents such as chlorthalidone and indapamide are preferred thiazide-like diuretics due to better cardiovascular outcomes 2, 3
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 and particularly beneficial in patients with specific comorbidities (diabetes, chronic kidney disease, heart failure) 1, 4
Population-Specific Considerations
For Black patients, thiazide diuretics or CCBs are preferred first-line agents 1, 2
For patients with albuminuria (urine albumin-to-creatinine ratio ≥300 mg/g creatinine), ACE inhibitors or ARBs are strongly recommended as first-line therapy 2, 1
For patients with established coronary artery disease, ACE inhibitors or ARBs are recommended first-line 2, 1
For patients aged 55 or older or Black patients of any age, calcium channel blockers (C) or diuretics (D) are generally more effective first-line agents 2
For patients younger than 55 and white, ACE inhibitors or ARBs may be more effective as initial treatment 2
Monotherapy vs. Combination Therapy
For most hypertensive patients, a single-pill combination initially containing two drug classes at low doses is recommended 2
For BP ≥140/90 mmHg, upfront combination therapy (either as separate pills or as single-pill combinations) is recommended 2
For BP ≥160/100 mmHg, initial treatment with two antihypertensive medications is recommended to more effectively achieve adequate blood pressure control 2, 5
Single-pill combinations may improve medication adherence in some individuals 2, 5
Evidence Supporting Thiazide Diuretics
Compared with placebo, low-dose thiazide diuretics have been shown to reduce all-cause mortality in hypertensive patients, preventing about 2-3 deaths and 2 strokes per 100 patients treated for 4-5 years 3
The efficacy of chlorthalidone is supported by the highest-level evidence from three comparative clinical trials versus placebo, an ACE inhibitor, or a calcium-channel blocker, in more than 50,000 patients 3
In one trial, chlorthalidone was superior to the ACE inhibitor lisinopril in preventing stroke and superior to the calcium-channel blocker amlodipine in preventing heart failure 3
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, 2
The combination of two RAS blockers (ACE inhibitors and ARBs) is not recommended due to increased risk of adverse effects without additional benefit 2
Alpha-blockers should not be used as first-line therapy due to inferior cardiovascular protection compared to other agents 1
Thiazide diuretics can cause hyperglycemia and diabetes, although this does not reduce their efficacy in preventing cardiovascular events 3
For resistant hypertension (BP still uncontrolled under maximally tolerated triple-combination therapy), spironolactone should be considered as a fourth agent 2