Best Antihypertensive Medications for Blood Pressure Control
Initial Therapy Selection
For most patients with hypertension, initial therapy should include thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or long-acting dihydropyridine calcium channel blockers, as these drug classes have demonstrated cardiovascular event reduction in clinical trials. 1
First-Line Medication Classes and Dosing
ACE Inhibitors:
- Lisinopril: Start 10 mg once daily, titrate to 20-40 mg daily (maximum 80 mg, though doses above 40 mg show minimal additional benefit) 2
- Benazepril: Typical dosing 20-40 mg daily 3
- These agents are particularly beneficial for patients with coronary artery disease, diabetes with albuminuria (UACR ≥30 mg/g), or chronic kidney disease 1
Angiotensin Receptor Blockers (ARBs):
- Losartan: Start 50 mg once daily, may increase to 100 mg daily if needed 4
- Candesartan, valsartan, olmesartan: Alternative ARBs with similar efficacy 5
- Preferred when ACE inhibitors cause cough; equally effective for cardiovascular protection 1
Thiazide-Like Diuretics:
- Chlorthalidone: Start 12.5-25 mg once daily (preferred over hydrochlorothiazide due to longer duration and superior cardiovascular outcomes) 6, 3
- Hydrochlorothiazide: 12.5-25 mg daily if chlorthalidone unavailable 1
- Indapamide: 1.25-2.5 mg daily 7
- Critical caveat: Doses above 25 mg chlorthalidone significantly increase hypokalemia risk in elderly patients without substantial additional BP reduction 8
Calcium Channel Blockers (Dihydropyridine):
- Amlodipine: Start 2.5-5 mg once daily, titrate to maximum 10 mg daily 3, 8
- Particularly effective in elderly patients and Black patients 1, 3
- May reduce ACE inhibitor-induced peripheral edema when combined 3
Combination Therapy Strategy
Multiple-drug therapy is generally required to achieve BP <130/80 mmHg, with most patients needing 2-3 agents. 1
When to Initiate Dual Therapy
For BP ≥150/90 mmHg: Start with two antihypertensive medications immediately to achieve control more rapidly 1
For BP 130-150/80-90 mmHg: May start with single agent, but be prepared to add second agent if target not reached within 3 months 1
Preferred Two-Drug Combinations
ACE inhibitor or ARB + Calcium channel blocker 3, 5
- Complementary mechanisms: vasodilation plus renin-angiotensin system blockade
- Superior BP control compared to either agent alone
- Reduces peripheral edema from CCB
ACE inhibitor or ARB + Thiazide diuretic 1, 3
- Particularly effective for volume-dependent hypertension
- Standard combination for patients with diabetes or chronic kidney disease
Calcium channel blocker + Thiazide diuretic 3
- More effective than CCB + ACE inhibitor/ARB in Black patients
- Good option when renin-angiotensin system blockers contraindicated
Standard Three-Drug Combination
ACE inhibitor or ARB + Calcium channel blocker + Thiazide diuretic represents guideline-recommended triple therapy 3, 7
- Targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction
- Should be optimized before considering fourth agent
- Single-pill combinations improve adherence 1
Special Population Considerations
Patients with Diabetes
- First-line: ACE inhibitor or ARB (especially with albuminuria UACR ≥30 mg/g) 1
- Alternative: Thiazide diuretics or dihydropyridine CCBs if no albuminuria 1
- Target BP: <130/80 mmHg 1
Patients with Coronary Artery Disease
- First-line: ACE inhibitor or ARB 1
- Add beta-blocker if history of MI, active angina, or heart failure with reduced ejection fraction 1
Patients with Chronic Kidney Disease
- First-line: ACE inhibitor or ARB, particularly with albuminuria 1
- Continue even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 1
- Monitor potassium and creatinine 7-14 days after initiation or dose change 1
Black Patients
- First-line: Thiazide diuretic or dihydropyridine CCB 3, 9
- ACE inhibitors/ARBs less effective as monotherapy but effective in combination 1, 3
Elderly Patients (≥65 years)
- Start with lower doses (e.g., amlodipine 2.5 mg) and titrate gradually 8
- Target BP: <140/90 mmHg minimum; <130/80 mmHg if well-tolerated 7, 8
- Avoid chlorthalidone >12.5 mg due to hypokalemia risk 8
Resistant Hypertension Management
Resistant hypertension is defined as BP ≥140/90 mmHg despite three drugs (including a diuretic) at optimal doses. 1
Fourth-Line Agent
Spironolactone 25-50 mg daily is the preferred fourth-line agent 1, 3, 7
- Provides additional BP reductions of 20-25/10-12 mmHg
- Monitor potassium closely when combined with ACE inhibitor or ARB 3
- Check potassium and creatinine 1-2 weeks after initiation 7
Before Diagnosing Resistant Hypertension
- Confirm medication adherence (most common cause of apparent resistance) 1, 3
- Rule out white coat hypertension with home BP monitoring 3
- Exclude secondary causes: primary aldosteronism, renal artery stenosis, obstructive sleep apnea 3, 7
- Address barriers to medication taking (cost, side effects) 1
Critical Monitoring Parameters
Check serum potassium and creatinine:
- 7-14 days after starting ACE inhibitor, ARB, or mineralocorticoid receptor antagonist 1
- Monitor for hypokalemia with diuretics 1
- Monitor for hyperkalemia with ACE inhibitors/ARBs/spironolactone 3, 7
Reassess BP:
- Within 2-4 weeks after any medication change 3, 7
- Goal: achieve target BP within 3 months of initiating or modifying therapy 1, 3
Important Contraindications and Pitfalls
Never combine ACE inhibitor with ARB - increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 1, 3
Avoid in pregnancy: ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors are contraindicated 1
Beta-blockers are NOT first-line unless compelling indication (post-MI, angina, heart failure with reduced ejection fraction) - they do not reduce mortality as BP-lowering agents alone 1, 3
Bedtime dosing is NOT recommended - no proven benefit over morning dosing 1
Do not delay treatment intensification - stage 2 hypertension (≥160/100 mmHg) requires immediate dual therapy 1