What is the recommended treatment approach for a patient with hypertension, considering lifestyle modifications and medication options?

Hypertension Treatment Approach

For most patients with hypertension, treatment should begin with lifestyle modifications, and pharmacologic therapy should be initiated with a thiazide or thiazide-like diuretic, ACE inhibitor or ARB, or calcium channel blocker, titrated to achieve a blood pressure target of <130/80 mm Hg for adults under 65 years and <130 mm Hg systolic for those 65 years and older. 1, 2, 3

Initial Assessment and Diagnosis Confirmation

• Confirm the diagnosis using home blood pressure monitoring (≥135/85 mm Hg) or 24-hour ambulatory monitoring (≥130/80 mm Hg) in addition to office readings, as clinic measurements may overestimate true blood pressure 2, 4
• Calculate body mass index and assess alcohol consumption in all patients, and evaluate sodium intake and stress levels in hypertensive patients 1
• Screen for secondary causes of hypertension if blood pressure is refractory (≥5 drugs including a diuretic with BP above goal), if there is unprovoked hypokalemia, or if diastolic hypertension develops in patients ≥65 years 1

Lifestyle Modifications (First-Line for All Patients)

All patients with elevated blood pressure or hypertension should implement lifestyle changes, which can reduce blood pressure by 10-20 mm Hg and may eliminate the need for medications in some cases. 1, 3

• Sodium restriction: Reduce intake to <1500 mg/day, or at minimum achieve an absolute reduction of 1000 mg/day 1
• Weight management: Achieve and maintain ideal body weight, or lose at least 1 kg if overweight (target BMI 20-25 kg/m²) 1, 2
• Dietary potassium: Increase intake to 3500-5000 mg/day through diet 1
• Physical activity: Engage in aerobic or dynamic resistance exercise for 90-150 minutes per week, or isometric resistance training 3 sessions per week 1
• Alcohol moderation: Limit to ≤2 drinks per day for men and ≤1 per day for women (maximum 14/week for men, 9/week for women) 1, 5
• DASH diet: Follow a dietary pattern rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated and total fat 1

The blood pressure-lowering effects of these interventions are partially additive and enhance the efficacy of pharmacologic therapy 3, 6

Indications for Pharmacologic Therapy

Initiate antihypertensive medication based on blood pressure level and cardiovascular disease risk, not solely on the blood pressure threshold of 130/80 mm Hg. 1, 3

• Stage 1 hypertension (130-139/80-89 mm Hg): Start medication if the patient has established cardiovascular disease, diabetes, chronic kidney disease, or high atherosclerotic CVD risk 1, 3
• Stage 2 hypertension (≥140/90 mm Hg): Initiate pharmacologic therapy in all patients 1, 3
• Elevated BP (120-129/<80 mm Hg): Lifestyle modifications alone; recheck every 3-6 months 1

First-Line Medication Options

The three first-line drug classes are thiazide or thiazide-like diuretics, ACE inhibitors or ARBs, and calcium channel blockers. 1, 2, 3

Selection Based on Patient Characteristics:

• Black patients: Prefer a calcium channel blocker or thiazide diuretic over ACE inhibitor/ARB as initial monotherapy, as ACE inhibitors are less effective in this population 1, 2, 7
• Non-Black patients: Any of the three first-line classes is appropriate 2, 3
• Patients with diabetes and albuminuria: Initiate with an ACE inhibitor or ARB 1
• Patients with chronic kidney disease: Start with an ACE inhibitor or ARB (use ARB if ACE inhibitor not tolerated) 1, 2
• Patients with heart failure: Use an ACE inhibitor or ARB 1, 2
• Patients with atrial fibrillation: Favor an ARB, which may reduce recurrence 1
• Patients with coronary artery disease: ACE inhibitor or ARB combined with a calcium channel blocker is beneficial 2

Specific Drug Recommendations:

• Thiazide-like diuretics: Chlorthalidone 12.5-25 mg daily is preferred over hydrochlorothiazide due to longer duration of action and proven cardiovascular disease reduction 2, 8
• ACE inhibitors: Lisinopril 10-40 mg daily or enalapril 7, 3
• ARBs: Candesartan, olmesartan, or valsartan 2, 3
• Calcium channel blockers: Amlodipine 5-10 mg daily 2, 3

Combination Therapy Algorithm

Most patients will require two or more medications to achieve blood pressure control. 1, 2, 3

Stepwise Approach:

1. Start with one first-line agent and titrate to maximum tolerated dose over 2-4 weeks 2, 4
2. Add a second agent from a different class if blood pressure remains uncontrolled:
   • For non-Black patients: ACE inhibitor/ARB + calcium channel blocker, or ACE inhibitor/ARB + thiazide diuretic 2, 4
   • For Black patients: Calcium channel blocker + thiazide diuretic is more effective than calcium channel blocker + ACE inhibitor/ARB 2
3. Add a third agent if blood pressure remains ≥140/90 mm Hg after optimizing two drugs:
   • The standard triple therapy is ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic 2, 3
4. Add spironolactone 25-50 mg daily as the preferred fourth-line agent for resistant hypertension (uncontrolled on three drugs including a diuretic) 2, 4

Important Combination Considerations:

• Never combine an ACE inhibitor with an ARB, as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 2, 4
• Adding a calcium channel blocker to an ACE inhibitor/ARB may attenuate peripheral edema caused by the calcium channel blocker alone 2
• Single-pill combinations improve adherence and should be used when possible 4

Blood Pressure Targets

• Adults <65 years: <130/80 mm Hg 1, 2, 3
• Adults ≥65 years: <130 mm Hg systolic 1, 2
• Patients with diabetes or chronic kidney disease: <130/80 mm Hg 1, 8
• Higher-risk patients (if well tolerated): 120-129 mm Hg systolic 2

Monitoring and Follow-Up

• Patients initiating drug therapy: Follow approximately monthly for dose titration until blood pressure is controlled 1
• After medication adjustments: Reassess within 2-4 weeks to allow full effect of dose changes 2, 4
• Goal timeline: Achieve target blood pressure within 3 months of initiating or modifying therapy 2, 4
• Once controlled: Monitor blood pressure every 3-6 months 1
• Laboratory monitoring: Check serum potassium and creatinine 2-4 weeks after initiating ACE inhibitors, ARBs, or diuretics to detect hyperkalemia, hypokalemia, or changes in renal function 2

Critical Pitfalls to Avoid

• Do not delay treatment intensification in patients with stage 2 hypertension or uncontrolled blood pressure, as this increases cardiovascular risk 2
• Do not add a third drug class before maximizing doses of the current two-drug regimen—this violates guideline-recommended stepwise approaches 2, 4
• Always verify medication adherence before adding additional agents, as non-adherence is the most common cause of apparent treatment resistance 2, 4
• Do not use beta-blockers as first-line therapy unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation requiring rate control) 2
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure 2

Resistant Hypertension Management

If blood pressure remains uncontrolled (≥140/90 mm Hg) despite adherence to three optimally dosed medications including a diuretic, the patient has resistant hypertension. 1, 2

• Rule out secondary causes: primary aldosteronism (prevalence ~20% in resistant hypertension), sleep apnea, renal artery stenosis, medication interference 1
• Add spironolactone 25-50 mg daily as the preferred fourth agent, monitoring potassium closely when combined with ACE inhibitor/ARB 2, 4
• Alternative fourth-line agents if spironolactone is contraindicated: amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 2
• Refer to a hypertension specialist if blood pressure remains uncontrolled on four-drug therapy at optimal doses 2, 4