What is the best medication for treating hypertension?

Best Medications for Hypertension Management

The best medications for treating hypertension are thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), which should be selected based on patient characteristics and comorbidities. 1

First-Line Medication Options

Recommended First-Line Agents

The World Health Organization (WHO) and major cardiology societies recommend the following as first-line medications for hypertension:

1. Thiazide and thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide, indapamide)
2. ACE inhibitors (e.g., lisinopril, enalapril)
3. ARBs (e.g., candesartan, valsartan)
4. Long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) 1

Medication Selection Algorithm

• For most patients without comorbidities: Any of the four first-line agents can be used
• For Black patients: Calcium channel blocker or thiazide diuretic as initial therapy 2, 1
• For patients with diabetes or CKD: ACE inhibitor or ARB preferred 2, 1
• For patients with heart failure: ACE inhibitor/ARB, beta-blocker, mineralocorticoid receptor antagonist 2, 1
• For patients with coronary artery disease: RAS blockers, beta-blockers with or without CCBs 1

Combination Therapy

Single-pill combinations are preferred to improve adherence 1. The WHO suggests combination therapy as an initial treatment, particularly for:

• Patients with BP significantly above target (>20/10 mmHg above goal)
• Black patients
• Patients with high cardiovascular risk 1

Recommended Combinations:

• ACE inhibitor or ARB + dihydropyridine CCB
• ACE inhibitor or ARB + thiazide/thiazide-like diuretic
• CCB + thiazide/thiazide-like diuretic 1

Avoid These Combinations:

• ACE inhibitor + ARB (increased risk of adverse effects) 1, 2
• ACE inhibitor or ARB + direct renin inhibitor 2

Treatment Intensification

For patients not reaching target BP on dual therapy:

1. Triple therapy: ACE inhibitor/ARB + CCB + thiazide/thiazide-like diuretic
2. If still uncontrolled, add spironolactone (25-50 mg/day)
3. If spironolactone is not tolerated, consider eplerenone, beta-blocker, alpha-blocker, or centrally acting agent 1, 2

Blood Pressure Targets

• Initial target for all patients: <140/90 mmHg 1
• Optimal target for most patients: 120-129/<80 mmHg (if tolerated) 1
• For older adults (≥65 years): 130-139 mmHg systolic 1
• For very elderly (≥85 years) or those with orthostatic hypotension: Consider more lenient targets (<140/90 mmHg) 1

Medication-Specific Considerations

Thiazide Diuretics

• Low-dose thiazides have shown reduction in mortality, stroke, and coronary heart disease 3
• Chlorthalidone may be preferred over hydrochlorothiazide due to longer duration of action and stronger evidence in landmark trials 1

ACE Inhibitors

• Reduce mortality, stroke, coronary heart disease, and cardiovascular events 3
• Lisinopril has been shown to effectively reduce blood pressure with once-daily dosing 4
• May cause dry cough in some patients

Calcium Channel Blockers

• Effective at reducing stroke and cardiovascular events 3
• Well-tolerated in most patient populations
• Particularly effective in Black patients 1

Common Pitfalls and Caveats

1. Inadequate dosing: Ensure medications are titrated to effective doses before adding additional agents
2. Ignoring adherence issues: Single-pill combinations improve adherence 1
3. Overlooking secondary causes: Consider screening for secondary hypertension in resistant cases
4. Not accounting for white coat hypertension: Home BP monitoring is recommended for medication titration 2
5. Drug interactions: Be aware of potential interactions, particularly with CCBs and certain antiretroviral therapies 1

Monitoring Recommendations

• Follow up within 1 month for BP 130-139/80-89 mmHg
• Follow up within 2-4 weeks for BP 140-159/90-99 mmHg
• Follow up within 1-2 weeks for BP ≥160/100 mmHg 2
• Monitor serum creatinine, eGFR, and potassium within 2-4 weeks of starting ACE inhibitors, ARBs, or diuretics 2

Remember that blood pressure control is the primary goal, regardless of which medication is used, as it is the reduction in blood pressure that provides cardiovascular benefit rather than specific properties of individual drugs 5, 6.