What are the first-line medications for managing hypertension?

First-Line Medications for Managing Hypertension

The first-line medications for managing hypertension include thiazide or thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). 1

Initial Drug Selection

• For most patients with hypertension, a combination of two first-line agents at low doses (typically as a single-pill combination) is recommended as initial therapy, which provides more effective blood pressure control than monotherapy 1
• The major four drug classes recommended as first-line therapy are:
  • ACE inhibitors (e.g., lisinopril) 2
  • ARBs (e.g., losartan) 3
  • Dihydropyridine calcium channel blockers (CCBs) 1
  • Thiazide or thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide) 1, 4

Patient-Specific Considerations

Race/Ethnicity Considerations

• For Black patients, CCBs or thiazide diuretics are more effective as initial therapy compared to ACE inhibitors 1
• ARBs may be better tolerated than ACE inhibitors in Black patients, with less cough and angioedema 1
• For patients from Sub-Saharan Africa, a CCB combined with either a thiazide diuretic or a RAS blocker (ACE inhibitor or ARB) should be considered 1

Comorbidity Considerations

• For patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), an ACE inhibitor or ARB is recommended as first-line therapy 1
• For patients with diabetes and established coronary artery disease, ACE inhibitors or ARBs are recommended first-line 1
• For patients with heart failure with reduced ejection fraction, guideline-directed medical therapy beta-blockers are recommended 1
• For patients with chronic kidney disease, ACE inhibitors or ARBs are preferred 1

Combination Therapy Approach

• For patients with BP between 130/80 mmHg and 160/100 mmHg, starting with a single drug may be appropriate 1
• For patients with BP ≥160/100 mmHg, initial therapy with two antihypertensive medications is recommended 1
• The combination of two RAS blockers (ACE inhibitor + ARB) is not recommended due to increased risk of adverse effects 1
• Single-pill combinations are preferred to improve medication adherence 1

Resistant Hypertension Management

• Resistant hypertension is defined as BP ≥140/90 mmHg despite treatment with three antihypertensive drugs including a diuretic 1
• For resistant hypertension, the addition of spironolactone to existing treatment is recommended 1
• If spironolactone is not tolerated, alternatives include:
  • Eplerenone 1
  • Beta-blockers (preferably vasodilating types like carvedilol, labetalol, or nebivolol) 1
  • Other potassium-sparing diuretics (amiloride, triamterene) 1
  • Alpha-blockers 1

Evidence on Comparative Effectiveness

• First-line thiazide diuretics have shown superior outcomes in preventing heart failure compared to CCBs and ACE inhibitors 1, 4
• CCBs are as effective as diuretics for reducing all cardiovascular events except heart failure 1
• Thiazide diuretics compared to ACE inhibitors may reduce stroke slightly (ARR 0.6%) 4
• When compared to alpha-blockers, thiazide diuretics significantly reduce heart failure (ARR 2.6%) and total cardiovascular events (ARR 3.1%) 4

Practical Approach to Initiation

1. Assess baseline cardiovascular risk and presence of comorbidities
2. For most patients with confirmed hypertension, start with a low-dose combination of two first-line agents (preferably as a single pill) 1
3. For patients with specific indications (CKD, diabetes with albuminuria), include an ACE inhibitor or ARB in the initial regimen 1
4. For Black patients, include a CCB or thiazide diuretic in the initial regimen 1
5. Titrate medication doses based on blood pressure response, aiming for target BP <130/80 mmHg in most patients 1, 5
6. If BP remains uncontrolled on two medications, add a third agent from a different class 1
7. For resistant hypertension, add spironolactone as a fourth agent 1

Common Pitfalls to Avoid

• Combining two RAS blockers (ACE inhibitor + ARB) increases adverse effects without additional benefit 1
• Using alpha-blockers as first-line therapy (less effective for cardiovascular event prevention) 1
• Inadequate dosing or insufficient time before adding additional agents 1
• Failing to consider adherence issues before diagnosing resistant hypertension 1
• Not accounting for race/ethnicity differences in medication response 1
• Overlooking the importance of lifestyle modifications alongside medication therapy 1