What is the initial approach to managing hypertension with anti-hypertensives (blood pressure medications)?

Initial Management of Hypertension with Antihypertensive Medications

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

Confirming the Diagnosis Before Treatment

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

Blood Pressure Thresholds and Treatment Intensity

Stage 1 Hypertension (140-159/90-99 mmHg)

• Begin with a single antihypertensive agent from first-line options for blood pressure between 130/80 mmHg and 160/100 mmHg 1, 3
• The American College of Cardiology recommends monotherapy for this range, with reassessment in 1 month 3

Stage 2 Hypertension (≥160/100 mmHg)

• Initiate treatment with two antihypertensive medications simultaneously from different classes, preferably as a single-pill combination 1, 3, 2
• Two-drug combination therapy achieves blood pressure control faster, improves adherence, and reduces cardiovascular risk more rapidly than sequential monotherapy 2
• Single-pill combinations are strongly preferred over separate pills to enhance medication adherence 2

First-Line Medication Classes

The four first-line antihypertensive drug classes are:

• ACE inhibitors (e.g., lisinopril 10 mg daily) 1, 4
• Angiotensin receptor blockers (ARBs) 1, 3
• Thiazide-like diuretics (chlorthalidone 12.5-25 mg daily preferred over hydrochlorothiazide) 1, 2, 5
• Dihydropyridine calcium channel blockers (e.g., amlodipine 5 mg daily) 1, 3

Evidence-Based Medication Selection

• Chlorthalidone is preferred over hydrochlorothiazide due to its longer half-life and superior cardiovascular outcome data, with the highest-level evidence from trials involving over 50,000 patients 3, 5
• Thiazide diuretics and ACE inhibitors are the only classes shown to reduce all-cause mortality in hypertensive patients, preventing approximately 2-3 deaths and 2 strokes per 100 patients treated for 4-5 years 5
• In head-to-head trials, chlorthalidone was superior to lisinopril in preventing stroke and superior to amlodipine in preventing heart failure 5

Preferred Two-Drug Combinations for Stage 2 Hypertension

Effective and well-tolerated combinations include:

• Thiazide diuretic + ACE inhibitor (e.g., chlorthalidone 12.5-25 mg + lisinopril 10 mg) 2
• Thiazide diuretic + ARB 2
• Calcium channel blocker + ACE inhibitor 2
• Calcium channel blocker + ARB 2

Special Population Considerations

Patients with Diabetes

• Use an ACE inhibitor or ARB as first-line therapy to reduce risk of progressive kidney disease 1, 3
• This is mandatory in patients with diabetes and albuminuria (UACR ≥30 mg/g) 3, 2

Patients with Chronic Kidney Disease or Albuminuria

• Initial treatment must include an ACE inhibitor or ARB at maximum tolerated dose to reduce risk of progressive kidney disease 1, 3

Black Patients

• Initial therapy should include a diuretic or calcium channel blocker, either alone or in combination with a RAS blocker 2
• For two-drug therapy, use ARB + calcium channel blocker or calcium channel blocker + thiazide diuretic, as Black patients have reduced response to ACE inhibitors as monotherapy 3

Pregnant Women or Those Planning Pregnancy

• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors are absolutely contraindicated due to risk of fetal injury and death 3, 2
• Use calcium channel blockers or methyldopa instead 2

Patients with Established Cardiovascular Disease

• ACE inhibitors or ARBs are recommended as first-line therapy 3

Patients with Heart Failure

• Beta-blockers are indicated in addition to other agents 3

Lifestyle Modifications (Concurrent with Medication)

Implement these evidence-based lifestyle interventions simultaneously with pharmacologic therapy:

• DASH eating pattern: 8-10 servings/day of fruits and vegetables, 2-3 servings/day of low-fat dairy products, reduced saturated/trans fats 1, 3
• Sodium restriction: <2,300 mg/day (ideally <1,500 mg/day) 1, 3, 2
• Increased potassium intake: 3,500-5,000 mg/day through dietary sources 1, 3
• Physical activity: At least 150 minutes of moderate-intensity aerobic activity per week 3
• Weight loss if overweight/obese 3, 2
• Alcohol moderation: ≤2 drinks/day for men, ≤1 drink/day for women 3
• Smoking cessation 3

Titration Strategy and Follow-Up

• 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
• For lisinopril, the usual dosage range is 20-40 mg per day, with doses up to 80 mg studied but not providing greater effect 4
• Continue monthly visits until blood pressure target is achieved 2

Blood Pressure Targets

• Target <130/80 mmHg for most adults <65 years 1, 2
• 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

Monitoring and Safety

• Monitor serum creatinine/eGFR and potassium levels 7-14 days after starting or adjusting doses of ACE inhibitors, ARBs, or diuretics, then at least annually 1, 2
• Watch for hypokalemia when using diuretics 1, 3
• Avoid ACE inhibitors in patients with history of angioedema 2
• Use ACE inhibitors/ARBs cautiously in patients with severe bilateral renal artery stenosis due to acute renal failure risk 2

Critical Pitfalls to Avoid

• Do not delay pharmacotherapy for a trial of lifestyle modification alone in patients with BP ≥140/90 mmHg 3
• Avoid sequential monotherapy as the default approach in high-risk patients or those with BP ≥160/100 mmHg, as it delays blood pressure control 2
• Do not use hydrochlorothiazide when chlorthalidone is available, as longer-acting thiazide-like diuretics are preferred 3
• Avoid beta-blockers as initial therapy unless a specific indication exists (heart failure, coronary disease) 3
• Do not use the thiazide + beta-blocker combination in patients with metabolic syndrome or high diabetes risk due to dysmetabolic effects 2
• Avoid immediate-release nifedipine and hydralazine for acute blood pressure management 6

Resistant Hypertension (Not Controlled on Three Drugs)

• Ensure the three-drug regimen includes a diuretic and consists of an ACE inhibitor/ARB, calcium channel blocker, and thiazide diuretic 1, 3
• Add spironolactone 25 mg daily as a fourth agent if blood pressure remains uncontrolled 3, 2
• Reinforce lifestyle measures, especially sodium restriction 2
• Assess medication adherence, as poor compliance is the most common cause of resistant hypertension 2
• Exclude secondary causes (obstructive sleep apnea, renal artery stenosis, primary aldosteronism) 2