What is the initial approach for managing hypertension with oral drugs, such as Angiotensin-Converting Enzyme (ACE) inhibitors?

Management of Hypertension with Oral Drugs

For most adults with confirmed hypertension ≥140/90 mmHg, initiate pharmacologic therapy immediately alongside lifestyle modifications using a single first-line agent (ACE inhibitor, ARB, thiazide-like diuretic, or dihydropyridine calcium channel blocker), but if blood pressure is ≥160/100 mmHg, start with two agents simultaneously, preferably as a single-pill combination. 1, 2

Confirming the Diagnosis Before Treatment

• Confirm hypertension using out-of-office measurements—either home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg)—rather than relying solely on office readings before initiating treatment. 1, 2

Lifestyle Modifications (Initiate Immediately)

• Implement a DASH-style eating pattern emphasizing 8-10 servings/day of fruits and vegetables, 2-3 servings/day of low-fat dairy products, and reduced saturated/trans fats. 3, 1
• Restrict sodium intake to <2,300 mg/day (ideally <1,500 mg/day). 1, 2
• Increase potassium intake through dietary sources (3,500-5,000 mg/day). 1, 4
• Achieve caloric restriction if overweight (BMI ≥25 kg/m²) to promote weight loss. 1, 2
• Engage in at least 150 minutes of moderate-intensity aerobic exercise per week. 1, 4
• Limit alcohol intake to ≤2 drinks/day for men, ≤1 drink/day for women. 1, 2
• Recommend smoking cessation for all patients. 1, 2

Initial Pharmacologic Therapy Strategy

For Blood Pressure 140-159/90-99 mmHg:

• Start with a single antihypertensive agent from first-line options: ACE inhibitors, ARBs, thiazide-like diuretics (chlorthalidone or indapamide preferred over hydrochlorothiazide), or dihydropyridine calcium channel blockers. 3, 1
• All four classes are equally effective at reducing cardiovascular events in the general population. 1
• For ACE inhibitor therapy, lisinopril 10 mg once daily is an appropriate starting dose, with usual dosage range of 20-40 mg per day. 5

For Blood Pressure ≥160/100 mmHg:

• Initiate pharmacologic treatment with two antihypertensive medications simultaneously from different classes, preferably as a single-pill combination to improve adherence. 3, 1, 2
• Recommended two-drug combinations include: thiazide diuretic + ACE inhibitor, thiazide diuretic + ARB, calcium channel blocker + ACE inhibitor, or calcium channel blocker + ARB. 2, 4
• A specific effective combination is chlorthalidone 12.5-25 mg daily plus lisinopril 10 mg daily, as this has strong evidence for reducing cardiovascular events. 2

Special Population Considerations

Patients with Diabetes:

• Use ACE inhibitor or ARB as first-line therapy to reduce risk of progressive kidney disease. 3, 1
• For blood pressure ≥160/100 mmHg in diabetic patients, start with two drugs or a single-pill combination. 3

Patients with Chronic Kidney Disease or Albuminuria:

• For patients with albuminuria (UACR ≥30 mg/g), initial treatment should include an ACE inhibitor or ARB at the maximum tolerated dose to reduce risk of progressive kidney disease. 3, 1, 2
• ACE inhibitors or ARBs are strongly recommended for UACR ≥300 mg/g creatinine. 3

Patients with Coronary Artery Disease:

• Use ACE inhibitor or ARB as first-line therapy for patients with established coronary artery disease. 3, 1, 2
• Add beta-blocker if history of myocardial infarction, active angina, or heart failure with reduced ejection fraction. 1

Black Patients:

• Initial therapy should include ARB + dihydropyridine calcium channel blocker or calcium channel blocker + thiazide-like diuretic, as Black patients have reduced response to ACE inhibitors as monotherapy. 1, 2

Pregnant or Planning Pregnancy:

• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors are absolutely contraindicated due to fetal injury and death. 2
• Use calcium channel blockers or methyldopa instead. 2

Titration Strategy

• Recheck blood pressure in 1 month after initiating therapy. 1, 2
• If starting with monotherapy, titrate to full dose of initial agent before adding a second drug. 1, 2
• For lisinopril, increase from 10 mg to 20-40 mg daily before adding additional agents. 2, 5
• If blood pressure is not controlled with single agent at full dose, add a second agent from a different class. 1, 2

Resistant Hypertension (Not Meeting Target on Three Drugs)

• Ensure the three-drug regimen includes a diuretic and consists of an ACE inhibitor/ARB, calcium channel blocker, and thiazide diuretic. 3, 2
• Before diagnosing resistant hypertension, exclude medication nonadherence, white coat hypertension, and secondary hypertension. 3
• Consider adding mineralocorticoid receptor antagonist (spironolactone 25 mg daily) for patients not meeting blood pressure targets on three classes of antihypertensive medications including a diuretic. 3, 2

Monitoring and Safety

• Monitor serum creatinine/estimated glomerular filtration rate and serum potassium levels 7-14 days after starting or adjusting doses of ACE inhibitors, ARBs, or diuretics, then at least annually. 3, 1, 2
• Watch for hyperkalemia with ACE inhibitors/ARBs (mean increase approximately 0.1 mEq/L, but 15% of patients may have increases >0.5 mEq/L). 5
• Watch for hypokalemia when using diuretics. 1, 2
• Avoid combining ACE inhibitors with ARBs, or combining ACE inhibitors/ARBs with direct renin inhibitors, due to lack of added cardiovascular benefit and increased rate of adverse events (hyperkalemia, syncope, acute kidney injury). 3

Blood Pressure Targets

• Target blood pressure of <130/80 mmHg for most adults <65 years. 1
• Target systolic <130 mmHg if well-tolerated for adults ≥65 years. 1
• For patients with diabetes, chronic kidney disease, or established cardiovascular disease, target <130/80 mmHg. 1

Common Pitfalls to Avoid

• Do not delay pharmacotherapy for a trial of lifestyle modification alone in patients with BP ≥140/90 mmHg—initiate both simultaneously. 1, 2
• Avoid using hydrochlorothiazide when chlorthalidone or indapamide are available, as longer-acting thiazide-like diuretics have superior cardiovascular outcome data. 2
• Do not use beta-blockers as initial therapy unless a specific indication exists (heart failure, coronary disease, post-myocardial infarction). 2
• Avoid ACE inhibitors in patients with history of angioedema or severe bilateral renal artery stenosis. 2
• Use thiazides cautiously in patients with gout or history of acute gout unless on uric acid-lowering therapy. 2