What are the recommended treatment guidelines, including medications and dosages, for a patient with hypertension, considering comorbidities such as diabetes, kidney disease, heart failure, or coronary artery disease?

Hypertension Management: Guidelines, Medications, and Dosing

Blood Pressure Classification and Treatment Thresholds

For adults with confirmed hypertension (BP ≥140/90 mmHg), initiate dual-combination therapy immediately alongside lifestyle modifications, using a RAS blocker (ACE inhibitor or ARB) plus either a calcium channel blocker or thiazide diuretic. 1

• Blood pressure categories: Normal (<120/80 mmHg), Elevated (120-129/<80 mmHg), Stage 1 Hypertension (130-139/80-89 mmHg), Stage 2 Hypertension (≥140/90 mmHg) 1
• Confirm diagnosis with out-of-office measurements: home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg 1
• For BP between 130/80 mmHg and 150/90 mmHg, begin with a single drug 2
• For BP ≥150/90 mmHg, start with two antihypertensive medications to achieve goals more effectively 2

Blood Pressure Targets

Target BP <130/80 mmHg for most patients, with a minimum acceptable target of <140/90 mmHg. 2, 1

• For patients with diabetes: target <130/80 mmHg 2, 1
• For patients with chronic kidney disease or established cardiovascular disease: target <130/80 mmHg 1
• For elderly patients (≥65 years): target SBP <130 mmHg 3
• Optimal target: 120-129 mmHg systolic if well tolerated 1

Lifestyle Modifications (First-Line for All Patients)

All patients with BP >120/80 mmHg should implement lifestyle interventions: weight loss when indicated, DASH-style eating pattern with sodium <2,300 mg/day, increased potassium intake, alcohol moderation (≤2 drinks/day for men, ≤1 drink/day for women), smoking cessation, and at least 150 minutes of moderate-intensity aerobic activity per week. 2

Dietary Interventions

• Sodium restriction to <2,300 mg/day (ideally <1,500 mg/day) provides 5-10 mmHg systolic reduction 2, 1, 4
• DASH diet: 8-10 servings of fruits/vegetables per day, 2-3 servings of low-fat dairy products per day 2
• Increase potassium intake through dietary sources 2

Weight and Exercise

• Weight loss through caloric restriction for overweight patients 2
• At least 150 minutes of moderate-intensity aerobic activity per week 2
• Weight loss of 10 kg produces approximately 6.0 mmHg systolic and 4.6 mmHg diastolic reduction 5

Alcohol and Smoking

• Limit alcohol to ≤2 drinks/day for men, ≤1 drink/day for women 2
• Complete smoking cessation 2

First-Line Antihypertensive Medications

Initial treatment should include ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers—all demonstrated to reduce cardiovascular events in people with diabetes and hypertension. 2

ACE Inhibitors

• Lisinopril: Start 10 mg once daily, usual range 20-40 mg daily, maximum 80 mg daily 6
• For patients on diuretics: start 5 mg once daily 6
• Indicated for hypertension, heart failure, and post-MI mortality reduction 6

Angiotensin Receptor Blockers (ARBs)

• Losartan: Start 50 mg once daily, maximum 100 mg daily 7
• For patients with possible intravascular depletion (e.g., on diuretics): start 25 mg once daily 7
• For hepatic impairment: start 25 mg once daily 7

Calcium Channel Blockers

• Amlodipine: Typical dosing 5-10 mg once daily 5
• Preferred for Black patients as initial therapy over ACE inhibitors or ARBs 5

Thiazide-Like Diuretics

• Chlorthalidone: 12.5-25 mg once daily (preferred due to longer duration of action and superior cardiovascular outcomes) 5
• Hydrochlorothiazide: 12.5-25 mg once daily (alternative if chlorthalidone unavailable) 5
• Indapamide: 1.25-2.5 mg once daily 5

Special Population Considerations

Patients with Coronary Artery Disease

ACE inhibitors or ARBs are recommended as first-line therapy for hypertension in patients with diabetes and established coronary artery disease. 2

Patients with Albuminuria

For individuals with albuminuria (UACR ≥30 mg/g), initial treatment should include an ACE inhibitor or ARB to reduce the risk of progressive kidney disease. 2

• For UACR ≥300 mg/g: ACE inhibitor or ARB strongly recommended 2
• For UACR 30-299 mg/g: ACE inhibitor or ARB suggested 2
• Use maximum tolerated dose indicated for blood pressure treatment 2

Black Patients

• Dihydropyridine calcium channel blocker preferred as initial therapy 5
• Combination of calcium channel blocker plus thiazide diuretic may be more effective than calcium channel blocker plus ACE inhibitor/ARB 5

Pediatric Patients (≥6 years)

• Lisinopril: Start 0.07 mg/kg once daily (up to 5 mg total), maximum 0.61 mg/kg (up to 40 mg) once daily 6
• Losartan: Start 0.7 mg/kg once daily (up to 50 mg total), maximum 1.4 mg/kg (up to 100 mg) once daily 7
• Not recommended in children <6 years or with GFR <30 mL/min/1.73 m² 6, 7

Combination Therapy Algorithm

Two-Drug Combinations

Single-pill antihypertensive combinations improve medication adherence and should be used when available. 2, 1

• ACE inhibitor or ARB + calcium channel blocker 5
• ACE inhibitor or ARB + thiazide diuretic 5
• Calcium channel blocker + thiazide diuretic 5

Three-Drug Combinations

When BP remains uncontrolled on two drugs, add a third agent from the remaining class: ACE inhibitor or ARB + calcium channel blocker + thiazide diuretic. 5

• This combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 5
• Preferably use single-pill combinations to improve adherence 2

Four-Drug Therapy (Resistant Hypertension)

If BP remains uncontrolled despite optimized triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent. 5

• Spironolactone provides additional BP reductions of 20-25/10-12 mmHg when added to triple therapy 5
• Alternative fourth-line agents if spironolactone contraindicated: amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 5

Critical Monitoring Requirements

ACE Inhibitors, ARBs, and Diuretics

Monitor serum creatinine and potassium at routine visits and 7-14 days after initiation or dose change when using ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists. 2

• Monitor for hyperkalemia with ACE inhibitors and ARBs 2
• Monitor for hypokalemia with diuretics 2
• Check serum potassium and creatinine 2-4 weeks after initiating diuretic therapy 5

Pregnancy Considerations

ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception. 2

Medications to Avoid

Dual RAS Blockade

Never combine ACE inhibitors with ARBs, or combine ACE inhibitors or ARBs with direct renin inhibitors—this increases adverse events (hyperkalemia, syncope, acute kidney injury) without additional cardiovascular benefit. 2, 5

Beta-Blockers as Initial Therapy

• Do not use beta-blockers as first-line therapy unless compelling indications exist: angina, post-MI, heart failure with reduced ejection fraction, or need for heart rate control 5
• Beta-blockers are less effective than diuretics for stroke prevention and cardiovascular events 5

Follow-Up and Titration Schedule

Reassess BP within 2-4 weeks after any medication initiation or dose adjustment, with the goal of achieving target BP within 3 months of treatment initiation or modification. 5, 1

• Follow-up approximately monthly for drug titration until BP controlled 1
• Once BP consistently at target, annual follow-up 1
• An SBP reduction of 10 mmHg decreases risk of CVD events by approximately 20-30% 3

Common Pitfalls to Avoid

• Do not delay treatment intensification in patients with stage 2 hypertension (≥160/100 mmHg)—prompt action required to reduce cardiovascular risk 5
• Do not add a third drug class before maximizing doses of current two-drug regimen 5
• Do not assume treatment failure without first confirming medication adherence and ruling out secondary causes of hypertension 5
• Do not use monotherapy as initial treatment for confirmed hypertension (BP ≥140/90 mmHg) 1
• Verify medication adherence before escalating therapy, as non-adherence is the most common cause of apparent treatment resistance 5