What are the preferred modern antihypertensive medications?

Modern Preferred Antihypertensive Medications

The preferred modern antihypertensive medications are thiazide-type diuretics (particularly chlorthalidone), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), which should be selected based on patient-specific factors and comorbidities. 1

First-Line Antihypertensive Medications

Thiazide-Type Diuretics

• Chlorthalidone (12.5-25 mg daily) is preferred over other thiazide diuretics due to its longer half-life and proven cardiovascular disease reduction in clinical trials 1
• Hydrochlorothiazide (25-50 mg daily) is an alternative thiazide diuretic 1
• Indapamide (1.25-2.5 mg daily) is another option, particularly useful in patients with gout history who are on uric acid-lowering therapy 1
• Monitor for hyponatremia, hypokalemia, and changes in uric acid and calcium levels 1

ACE Inhibitors

• Options include lisinopril (10-40 mg daily), enalapril (5-40 mg daily), ramipril (2.5-20 mg daily), and others 1
• Particularly beneficial in patients with diabetes, left ventricular hypertrophy, heart failure, and chronic kidney disease 1
• Avoid in pregnancy and in patients with history of angioedema 1
• Monitor for hyperkalemia, especially in patients with CKD or those on potassium supplements 1

Angiotensin Receptor Blockers (ARBs)

• Options include losartan (50-100 mg daily), valsartan (80-320 mg daily), and others 1
• Indicated for hypertension, left ventricular hypertrophy, and diabetic nephropathy 2
• Alternative to ACE inhibitors in patients who develop cough 1
• Avoid in pregnancy and do not use in combination with ACE inhibitors 1

Calcium Channel Blockers (CCBs)

• Dihydropyridines (e.g., amlodipine 2.5-10 mg daily) are effective and well-tolerated 1
• Non-dihydropyridines (e.g., diltiazem, verapamil) may be beneficial in specific conditions like atrial fibrillation 1
• Particularly effective in Black patients and elderly patients with isolated systolic hypertension 1

Combination Therapy

• Most patients with stage 2 hypertension (≥140/90 mmHg) should be initiated on combination therapy with two agents of different classes 1
• Effective two-drug combinations include:
  • Thiazide diuretic + ACE inhibitor 1
  • Thiazide diuretic + ARB 1
  • CCB + ACE inhibitor 1
  • CCB + ARB 1, 3
• Fixed-dose combinations can improve adherence but may contain lower-than-optimal doses of the thiazide component 1
• Avoid simultaneous use of ACE inhibitor, ARB, and/or renin inhibitor as this is potentially harmful 1

Special Population Considerations

Black Patients

• Initial therapy should include a thiazide-type diuretic or CCB 1
• If using combination therapy, a diuretic and CCB is recommended 1

Patients with Diabetes

• ACE inhibitors or ARBs are preferred, especially with albuminuria 1
• For patients without albuminuria, any of the four main drug classes (thiazide diuretics, ACE inhibitors, ARBs, CCBs) can be used 1

Chronic Kidney Disease

• ACE inhibitors or ARBs are preferred, particularly with albuminuria ≥300 mg/day 1
• Target BP should be <130/80 mmHg 1

Heart Failure

• For heart failure with reduced ejection fraction (HFrEF): ACE inhibitors, ARBs, beta-blockers, diuretics, and mineralocorticoid receptor antagonists 1
• For heart failure with preserved ejection fraction (HFpEF): Diuretics for volume control, with ACE inhibitors or ARBs for additional BP control 1

Elderly Patients

• Diuretics and CCBs are particularly effective for isolated systolic hypertension 1
• Start with lower doses and titrate gradually 1

Resistant Hypertension

• Defined as BP ≥140/90 mmHg despite appropriate lifestyle management plus a diuretic and two other antihypertensive drugs at adequate doses 1
• Consider adding a mineralocorticoid receptor antagonist (e.g., spironolactone) 1
• Evaluate for secondary causes of hypertension, medication adherence issues, and white coat hypertension 1

Common Pitfalls to Avoid

• Avoid simultaneous use of ACE inhibitors and ARBs, which increases adverse effects without additional benefit 1
• Beta-blockers are no longer considered first-line for uncomplicated hypertension due to reduced stroke prevention compared to other agents 1
• Alpha-blockers (e.g., doxazosin) should not be used as initial therapy due to increased risk of heart failure compared to thiazide diuretics 1
• Avoid using non-dihydropyridine CCBs in patients with heart failure with reduced ejection fraction 1
• Monitor for metabolic effects with thiazide diuretics and beta-blockers, particularly in patients with metabolic syndrome or at risk for diabetes 1