What are the appropriate hypertension medication classes and their usage for different patient groups, including those with comorbidities such as diabetes, kidney disease, or heart failure?

Hypertension Medication Management by Patient Group

For most patients with hypertension, initiate dual-combination therapy immediately with an ACE inhibitor or ARB plus either a calcium channel blocker or thiazide-like diuretic, targeting blood pressure <130/80 mmHg. 1, 2

First-Line Medication Classes

The four evidence-based first-line antihypertensive classes that reduce cardiovascular events and mortality are 3, 4:

• ACE inhibitors (e.g., lisinopril) 5
• ARBs (e.g., losartan) 6
• Thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide) 4
• Dihydropyridine calcium channel blockers (e.g., amlodipine 5-10 mg daily) 7, 2

Medication Selection by Comorbidity

Chronic Kidney Disease (CKD)

• Mandatory first-line: ACE inhibitor or ARB regardless of other factors 3
• Use ARB if ACE inhibitor not tolerated 3
• This applies to any patient with albuminuria (UACR ≥30 mg/g) 3, 8

Diabetes Mellitus

• With albuminuria (UACR ≥30 mg/g): ACE inhibitor or ARB required 3, 8
• Without albuminuria: Any first-line drug class acceptable 3
• Target BP <130/80 mmHg 3, 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Favor: Guideline-directed medical therapy (GDMT) beta blockers (carvedilol, metoprolol succinate, bisoprolol) 3
• Avoid: Non-dihydropyridine calcium antagonists (diltiazem, verapamil) 3

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Favor: Diuretics for volume overload 3
• Add ACE inhibitor or ARB and beta blocker for additional BP control 3
• Consider angiotensin receptor-neprilysin inhibitor and mineralocorticoid receptor antagonists 3

Coronary Artery Disease

• Post-MI or acute coronary syndrome: GDMT beta blockers mandatory 3
• Stable ischemic heart disease: GDMT beta blockers plus ACE inhibitor or ARB 3, 8
• Angina: GDMT beta blockers; add dihydropyridine calcium antagonists for additional BP control 3

Atrial Fibrillation

• Favor: ARB (may reduce AF recurrence) 3

Post-Stroke (Secondary Prevention)

• Favor: Thiazide, ACE inhibitor, ARB, or thiazide + ACE inhibitor combination 3
• Restart drugs a few days post-event if previously treated 3
• Start treatment a few days post-event if BP ≥140/90 mmHg and not previously treated 3

Aortic Disease

• Favor: Beta blockers for thoracic aorta disease 3

Aortic Insufficiency

• Avoid: Beta blockers and non-dihydropyridine calcium antagonists (drugs that slow heart rate) 3

Post-Kidney Transplant

• Favor: Calcium antagonist (improves graft survival and GFR) 3
• Use with caution: ACE inhibitors 3
• First month post-transplant BP target <160/90 mmHg to avoid hypotension-induced graft thrombosis 3

Initial Therapy Algorithm

Stage 1 Hypertension (130-139/80-89 mmHg)

• BP 130-160/80-100 mmHg: May begin with single drug 3
• High-risk patients (CVD, CKD, diabetes, age 50-80): Start drug therapy immediately 8

Stage 2 Hypertension (≥140/90 mmHg or ≥160/100 mmHg)

• BP ≥160/100 mmHg: Initiate dual-combination therapy immediately 3, 8
• BP ≥150/90 mmHg: Consider dual therapy for more effective control 8

Preferred Combination Regimens

Recommended dual combinations 1, 2:

• ACE inhibitor or ARB + calcium channel blocker
• ACE inhibitor or ARB + thiazide-like diuretic

Critical contraindication: Never combine ACE inhibitor + ARB, or combine either with direct renin inhibitors (increased adverse events without benefit) 3, 2

Resistant Hypertension (BP ≥140/90 mmHg on 3+ drugs)

Definition: BP remains ≥140/90 mmHg despite appropriate lifestyle management plus a diuretic and two other antihypertensive drugs at adequate doses 3

Before diagnosing resistant hypertension, exclude 3:

• Medication non-adherence (address cost and side effects)
• White coat hypertension
• Secondary hypertension

Treatment: Add mineralocorticoid receptor antagonist (spironolactone) to existing regimen 3

Critical Monitoring Requirements

Serum creatinine and potassium monitoring 3, 1, 8:

• Check 7-14 days (or 2-4 weeks) after initiating or changing dose of ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, or diuretics
• Monitor at least annually thereafter 3
• Essential to detect hyperkalemia and acute kidney injury 3

BP reassessment 1, 8:

• Within 2-4 weeks after any medication initiation or dose adjustment
• Monthly visits until BP target achieved 8
• Achieve target BP within 3 months of treatment initiation or modification 1, 8

Lifestyle Modifications (Always Concurrent with Medications)

Sodium restriction: <1,500 mg/day (minimally reduce by 1,000 mg/day) provides 5-10 mmHg systolic reduction 3, 1

Potassium intake: 3,500-5,000 mg/day 3

Weight loss: Target ideal body weight or minimum 1 kg reduction (10 kg loss decreases BP by 6.0/4.6 mmHg) 3, 1

Physical activity: 90-150 minutes/week aerobic or dynamic resistance exercise, or 3 sessions/week isometric resistance 3, 1

Alcohol moderation: ≤2 drinks/day (men), ≤1 drink/day (women) 3

DASH diet: Rich in fruits, vegetables, whole grains, low-fat dairy; reduced saturated and total fat 3

Mnemonic for Hypertension Medication Classes

"ABCD" Approach:

• A = ACE inhibitors/ARBs (renin-angiotensin system blockers)
• B = Beta blockers (for specific indications: HFrEF, post-MI, angina)
• C = Calcium channel blockers (dihydropyridine type preferred)
• D = Diuretics (thiazide-like preferred)

Comorbidity-Specific Mnemonic "KIDNEYS FAIL HEARTS":

• Kidney disease → ACE inhibitor or ARB

• Ischemic heart disease → Beta blocker + ACE inhibitor/ARB

• Diabetes with albuminuria → ACE inhibitor or ARB

• Nephropathy (diabetic) → ACE inhibitor or ARB

• Ejection fraction reduced → GDMT beta blocker (avoid non-DHP CCB)

• Yielding volume overload (HFpEF) → Diuretics

• Stroke prevention → Thiazide ± ACE inhibitor

• Fibrillation (atrial) → ARB

• Aortic disease → Beta blocker

• Insufficiency (aortic valve) → Avoid beta blocker, non-DHP CCB

• Left ventricular hypertrophy → ARB (losartan)

• Heart failure preserved EF → Diuretics first

• Ejection fraction reduced → GDMT beta blocker

• Angina → Beta blocker + DHP CCB

• Renal transplant → Calcium antagonist

• Transplant (kidney) → Avoid ACE inhibitor early

• Stenosis (aortic, asymptomatic) → Start low, titrate slowly

Common Pitfalls to Avoid

Never use beta blockers as primary BP-lowering agents in absence of MI, angina, or HFrEF (no mortality benefit) 3

Bedtime dosing is not superior to morning dosing—dose timing should be based on patient preference and adherence 3

Single-pill combinations improve adherence—consider when multiple drugs needed 3, 2

Confirm diagnosis with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) before initiating treatment, as white coat hypertension affects 15-30% of patients 1