What is the best treatment for an adult patient with hypertension?

Treatment of Hypertension in Adults

For adults with newly diagnosed hypertension, initiate treatment with first-line agents—thiazide or thiazide-like diuretics (preferably chlorthalidone), ACE inhibitors, ARBs, or calcium channel blockers—with the choice guided by comorbidities and the goal of achieving blood pressure <130/80 mmHg for most adults. 1, 2

Blood Pressure Targets and Treatment Thresholds

Target blood pressure should be <130/80 mmHg for most adults, with individualized targets for elderly patients based on frailty status. 1, 3

When to Start Pharmacotherapy

• Stage 1 hypertension (140-159/90-99 mmHg): Start immediate drug therapy in high-risk patients (those with diabetes, chronic kidney disease, or cardiovascular disease); low-risk patients may trial lifestyle modifications for 3-6 months first. 1

• Stage 2 hypertension (≥160/100 mmHg): Start drug therapy immediately along with lifestyle modifications. 1

• Blood pressure 130-139/80-89 mmHg: Initiate lifestyle modifications; if targets not achieved after maximum 3 months, add pharmacologic treatment with agents that block the renin-angiotensin system. 4

First-Line Pharmacologic Agents

The preferred initial medications are thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, and calcium channel blockers, as these have been demonstrated to reduce cardiovascular events and mortality. 1, 2

Specific Drug Selection Strategy

• Thiazide-like diuretics: Chlorthalidone or indapamide are superior to hydrochlorothiazide for 24-hour blood pressure control and should be preferred. 3

• ACE inhibitors or ARBs: First-line choice for patients with diabetes, chronic kidney disease (especially with albuminuria), heart failure, or post-myocardial infarction. 4, 1, 5

• Calcium channel blockers: Appropriate as first-line agents, though dihydropyridine CCBs (like amlodipine) are preferred over non-dihydropyridines for most patients. 4, 1

• Beta-blockers: Not recommended as first-line unless specific indications exist (coronary artery disease, heart failure, post-MI, or arrhythmias). 1

Critical Prescribing Approach

Start with monotherapy at low dose and titrate to effective doses before adding new agents. 1 This prevents the common pitfall of therapeutic inertia—failing to intensify treatment when blood pressure remains uncontrolled. 3

Lifestyle Modifications (Essential for All Patients)

These interventions should be implemented regardless of whether pharmacotherapy is started:

• Sodium restriction: Reduce intake to <1,500 mg/day or at minimum reduce by 1,000 mg/day, which can lower blood pressure by 5-6 mmHg. 1, 3

• DASH diet: Emphasize fruits, vegetables, whole grains, low-fat dairy products, and reduced saturated fat. 1, 3

• Potassium supplementation: Increase intake to 3,500-5,000 mg/day. 1

• Weight reduction: Target 5-10% body weight loss if overweight (BMI >25 kg/m²), providing approximately 1 mmHg reduction per kg lost. 1, 3

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

• Alcohol moderation: Limit to ≤2 drinks per day for men and ≤1 per day for women. 1

Management of Comorbid Conditions

Diabetes Mellitus

Use ACE inhibitors or ARBs as first-line agents, particularly in patients with albuminuria, as these medications prevent progression of diabetic nephropathy. 4, 1 Target blood pressure is <130/80 mmHg. 4

• Monitor renal function and serum potassium when using ACE inhibitors or ARBs. 4
• Multiple drug therapy (two or more agents) is generally required to achieve targets. 4

Chronic Kidney Disease

ACE inhibitors or ARBs are the preferred agents for renoprotection. 1 Target blood pressure is <130/80 mmHg. 1

Coronary Artery Disease

Beta-blockers and ACE inhibitors/ARBs are recommended as first-line therapy. 1

Heart Failure

Use ACE inhibitors/ARBs, beta-blockers, and diuretics as the foundation of therapy. 1, 5

Valvular Heart Disease

• Aortic stenosis: Hypertension should be treated with pharmacotherapy, starting at low dose and gradually titrating upward; RAS blockade may be advantageous. 4
• Aortic insufficiency: Treat systolic hypertension with agents that do not slow heart rate (avoid beta-blockers). 4

Resistant Hypertension (Blood Pressure Uncontrolled on 3+ Medications)

If blood pressure remains uncontrolled despite three appropriately dosed medications including a diuretic, add spironolactone 25-50 mg daily as the preferred fourth agent, which provides superior blood pressure reduction (average 8-10 mmHg systolic). 3

Before Adding Fourth Agent

• Confirm true resistant hypertension using out-of-office measurements to exclude white coat effect. 3
• Assess medication adherence objectively through pharmacy refill records, as non-adherence accounts for up to 50% of apparent treatment failure. 3
• Replace hydrochlorothiazide with chlorthalidone or indapamide for superior 24-hour control. 3
• Screen for secondary causes: Primary aldosteronism (present in 15-20% of resistant cases), obstructive sleep apnea (present in ≥80%), renal artery stenosis, and medication interference (NSAIDs, decongestants, stimulants, oral contraceptives). 3, 6

Monitoring with Spironolactone

Monitor serum potassium and creatinine 2-4 weeks after initiation, as hyperkalemia risk increases with concurrent ACE inhibitor/ARB use. 3

Follow-Up and Monitoring Strategy

• Monthly visits for dose adjustments until blood pressure is controlled. 1
• Every 3-6 months once blood pressure is controlled. 1
• Confirm office readings with home or ambulatory blood pressure monitoring to avoid misdiagnosis of white coat hypertension. 1, 3
• Monitor medication adherence and side effects at each visit. 1

Common Pitfalls to Avoid

• Using hydrochlorothiazide instead of chlorthalidone/indapamide: The thiazide-like diuretics provide superior outcomes in resistant hypertension. 3

• Therapeutic inertia: Failing to intensify treatment when blood pressure remains uncontrolled at consecutive visits is the most common management error. 3

• Inadequate dose titration: Adding new agents before titrating existing medications to effective doses. 1, 3

• Assuming medication compliance: Up to 25% of patients don't fill initial prescriptions and only 20% maintain adequate adherence; verify objectively. 3

• Missing secondary causes: Screen for primary aldosteronism, obstructive sleep apnea, and renal artery stenosis in resistant hypertension. 3, 6

• Ignoring lifestyle modifications: These interventions are partially additive and enhance pharmacotherapy efficacy. 2