What is the recommended antihypertensive treatment strategy for patients with hypertension and comorbid conditions such as chronic kidney disease (eGFR < 60 mL/min/1.73 m²) or diabetes with albuminuria, heart failure with reduced ejection fraction, prior myocardial infarction or stable coronary artery disease, African or Caribbean ancestry, isolated systolic hypertension in adults over 65, asthma or chronic obstructive pulmonary disease, contraindications to ACE inhibitors/ARBs, and resistant hypertension?

Hypertension Treatment with Comorbidities

General Approach

All patients with hypertension and comorbidities should initiate lifestyle modifications alongside pharmacologic therapy, targeting BP <130/80 mmHg in most cases (<140/80 mmHg in elderly patients), with drug selection tailored to the specific comorbid condition to maximize cardiovascular and renal protection. 1

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Blood Pressure Targets by Population

• Standard target: <130/80 mmHg for most patients with comorbidities 1
• Elderly patients (≥65 years): <140/80 mmHg is acceptable, though <130/80 mmHg remains preferred if tolerated 1, 2
• Heart failure: Target 130/80 mmHg but maintain >120/70 mmHg to avoid excessive reduction 1
• Diabetes with hypertension: <130/80 mmHg 1

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Comorbidity-Specific Drug Selection

Chronic Kidney Disease (eGFR <60 mL/min/1.73 m²)

ACE inhibitors or ARBs are first-line therapy for CKD patients because they reduce albuminuria in addition to providing BP control. 1

• First-line: ACE inhibitor or ARB (use ARB if ACE inhibitor not tolerated) 1
• Additional agents: Add calcium channel blockers and diuretics as needed 1
• Diuretic selection: Use loop diuretics (furosemide, torsemide) when eGFR <30 mL/min/1.73 m² instead of thiazides 1, 3
• Monitoring: Check eGFR, microalbuminuria, and electrolytes (especially potassium and creatinine) at baseline, 7-14 days after initiation or dose change, and at routine visits 1
• Important: ACE inhibitors/ARBs may be continued even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 1

Diabetes with Albuminuria

For diabetic patients with albuminuria (UACR ≥30 mg/g), ACE inhibitors or ARBs are mandatory first-line therapy to reduce progressive kidney disease. 1

• UACR ≥30 mg/g: Start ACE inhibitor or ARB regardless of BP level 1
• No albuminuria: Any first-line agent (ACE inhibitor, ARB, thiazide-like diuretic, or dihydropyridine calcium channel blocker) is acceptable 1
• BP 130-150/80-90 mmHg: Begin with single agent 1
• BP ≥150/90 mmHg: Initiate two antihypertensive medications simultaneously for more effective control 1
• Monitoring: Check potassium and creatinine 7-14 days after starting or adjusting ACE inhibitor/ARB dose 1

Heart Failure with Reduced Ejection Fraction (HFrEF)

Guideline-directed medical therapy with beta-blockers (carvedilol, metoprolol succinate, or bisoprolol), ACE inhibitors/ARBs, and mineralocorticoid receptor antagonists form the foundation of treatment for HFrEF with hypertension. 1

• First-line: Guideline-directed beta-blockers (carvedilol, metoprolol succinate, bisoprolol) + ACE inhibitor or ARB + mineralocorticoid receptor antagonist 1
• Alternative to ACE inhibitor/ARB: Sacubitril-valsartan (ARNI) is indicated as alternative first-line therapy 1
• Diuretics: Add for symptomatic volume overload, though evidence limited to symptom improvement rather than mortality benefit 1
• Avoid: Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) 1
• Calcium channel blockers: Only add dihydropyridine types (amlodipine) if BP remains uncontrolled on above regimen 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Volume overload: Diuretics for symptomatic management 1
• Additional BP control: Add ACE inhibitor or ARB and beta-blocker 1
• Consider: Mineralocorticoid receptor antagonists and sacubitril-valsartan, though optimal strategy less established than HFrEF 1

Prior Myocardial Infarction or Stable Coronary Artery Disease

Beta-blockers and ACE inhibitors or ARBs are first-line therapy for hypertensive patients with coronary artery disease, providing both BP control and secondary prevention benefits. 1

• Post-MI/ACS: Guideline-directed beta-blockers (carvedilol, metoprolol succinate, bisoprolol) + ACE inhibitor or ARB 1
• Stable CAD: Beta-blockers + ACE inhibitor or ARB 1
• Angina: Beta-blockers first-line; add dihydropyridine calcium channel blockers for additional BP control 1
• Target: <130/80 mmHg 1
• Additional therapy: Lipid-lowering with LDL-C target <55 mg/dL (1.4 mmol/L) and antiplatelet therapy 1

Asthma or COPD

ARBs combined with calcium channel blockers and/or diuretics are preferred for hypertensive patients with obstructive lung disease, while beta-1 selective beta-blockers may be used cautiously in selected cases with compelling indications. 1

• Preferred regimen: ARB + calcium channel blocker and/or diuretic 1
• Beta-blockers: β1-selective agents (metoprolol, bisoprolol) may be used in selected patients with compelling indications (CAD, heart failure), but generally avoided 1
• Lifestyle: Smoking cessation mandatory; avoid environmental air pollution when possible 1

Isolated Systolic Hypertension in Adults >65 Years

Thiazide diuretics or dihydropyridine calcium channel blockers have the strongest evidence base for isolated systolic hypertension in elderly patients and should be initiated at low doses with gradual titration. 2

• First-line options: Thiazide diuretic (hydrochlorothiazide 12.5 mg daily) or dihydropyridine calcium channel blocker (amlodipine 2.5-5 mg daily) 2
• Alternative first-line: ACE inhibitors (lisinopril 5-10 mg daily) or ARBs are acceptable 2
• Target: <140/90 mmHg; for patients ≥80 years, systolic 140-145 mmHg acceptable if <140 mmHg not tolerated 2
• Critical monitoring: Always check standing BP to detect orthostatic hypotension 2
• Titration: Start with lowest dose and escalate gradually to minimize hypotension, falls, and treatment discontinuation 2
• Combination therapy: Most elderly patients require two or more drugs; preferred combinations include thiazide + ACE inhibitor, thiazide + calcium channel blocker, or ACE inhibitor + calcium channel blocker 2

Contraindications to ACE Inhibitors/ARBs

When ACE inhibitors and ARBs are contraindicated, calcium channel blockers combined with thiazide-like diuretics provide effective first-line therapy for most hypertensive patients. 1, 4

• First-line alternatives: Calcium channel blocker + thiazide-like diuretic 1, 4
• Absolute contraindications: Pregnancy, sexually active individuals of childbearing potential not using reliable contraception 1
• Relative contraindications: Bilateral renal artery stenosis, hyperkalemia, history of angioedema 1
• Post-kidney transplant: Calcium channel blockers preferred as they improve graft survival and GFR; use ACE inhibitors with caution 1

Resistant Hypertension

Resistant hypertension requires optimization of diuretic therapy based on renal function, with loop diuretics preferred when eGFR <30-40 mL/min/1.73 m², followed by addition of mineralocorticoid receptor antagonists or other fourth-line agents. 3

• Definition: BP uncontrolled on three agents including a diuretic at optimal doses 3
• Diuretic optimization: Switch to loop diuretics (furosemide 20-40 mg once or twice daily) if eGFR 30-70 mL/min/1.73 m², as thiazides lose efficacy 3
• Volume overload: Presence of edema indicates inadequate diuresis; intensify diuretic therapy 3
• Fourth-line agents: Consider mineralocorticoid receptor antagonists (if potassium permits), hydralazine 25-50 mg twice daily, or beta-blocker if compelling indication 3
• Monitoring: Recheck potassium, creatinine, and BP within 1-2 weeks after medication changes 3

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Lifestyle Modifications (Universal for All Comorbidities)

All hypertensive patients should implement comprehensive lifestyle changes, which lower BP, enhance medication efficacy, and reduce cardiovascular risk with minimal adverse effects. 1, 5, 4

• Sodium restriction: <2,300 mg/day (ideally <1,500 mg/day or at least 1,000 mg/day reduction) 1, 5
• Potassium supplementation: 3,500-5,000 mg/day through dietary sources 1, 4
• DASH diet: Increase fruits and vegetables (8-10 servings/day), low-fat dairy (2-3 servings/day), whole grains, reduced saturated and total fat 1, 5
• Weight loss: Target ideal body weight or minimum 1 kg reduction if overweight/obese 1, 4
• Physical activity: 90-150 minutes/week of aerobic or dynamic resistance exercise, or 3 sessions/week of isometric resistance 1, 4
• Alcohol moderation: ≤2 drinks/day in men, ≤1 drink/day in women 1, 4
• Smoking cessation: Mandatory, especially in COPD patients 1

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Monitoring and Follow-Up

• Newly diagnosed/uncontrolled: Monthly visits for medication titration until BP controlled 1
• Electrolyte monitoring: Check potassium and creatinine 7-14 days after initiating or changing dose of ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1, 3
• Diuretic monitoring: Check for hypokalemia at routine visits 1
• CKD patients: Monitor eGFR, microalbuminuria, and electrolytes regularly 1
• Elderly patients: Always assess for orthostatic hypotension with standing BP measurements 2

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Common Pitfalls to Avoid

• Do not use thiazide diuretics as monotherapy when eGFR <30-40 mL/min/1.73 m²—switch to loop diuretics for efficacy 3
• Do not discontinue ACE inhibitors/ARBs prematurely when creatinine rises modestly or eGFR declines to <30 mL/min/1.73 m²—cardiovascular benefits often outweigh risks 1
• Do not prescribe ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, or neprilysin inhibitors to sexually active individuals of childbearing potential without reliable contraception 1
• Do not use non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in heart failure with reduced ejection fraction 1
• Do not withhold treatment in patients ≥80 years based on age alone—treatment reduces stroke and mortality 2
• Do not start elderly patients on high doses or escalate rapidly—increases risk of hypotension, falls, and discontinuation 2
• Do not ignore volume overload in resistant hypertension—inadequate diuresis is a primary driver of treatment failure 3