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, initiate treatment with lifestyle modifications alongside pharmacotherapy using a thiazide or thiazide-like diuretic, ACE inhibitor or ARB, and 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 and older. 1, 2, 3

Initial Assessment and Diagnosis

• 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 white coat hypertension affects a significant proportion of patients 1, 2
• Screen for secondary causes in patients with resistant hypertension, unprovoked hypokalemia, or new-onset diastolic hypertension in those ≥65 years—specifically evaluate for sleep apnea, primary aldosteronism, and renal artery stenosis 1
• Assess cardiovascular risk and check for comorbidities (diabetes, chronic kidney disease, heart failure, coronary disease) as these guide drug selection 1, 2

Lifestyle Modifications (Essential for All Patients)

• Sodium restriction to <1,500 mg/day or at minimum reduce intake by 1,000 mg/day, which can lower blood pressure by 5-10 mm Hg 1, 4
• Weight loss if overweight/obese—target at least 1 kg reduction, as each kilogram lost reduces blood pressure by approximately 1 mm Hg 1, 3
• Increase dietary potassium to 3,500-5,000 mg/day through fruits and vegetables 1, 4
• Regular aerobic exercise for 90-150 minutes per week or dynamic resistance training 1, 3
• Limit alcohol consumption to ≤2 drinks daily for men and ≤1 drink daily for women 1, 3
• Adopt a DASH-like diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced saturated fat 1, 3

Pharmacotherapy Initiation

When to Start Medication

• Stage 1 hypertension (130-139/80-89 mm Hg) with high atherosclerotic cardiovascular disease risk or established cardiovascular disease 1, 3
• Stage 2 hypertension (≥140/90 mm Hg) regardless of cardiovascular risk 1, 3

First-Line Drug Classes

The three cornerstone drug classes are thiazide/thiazide-like diuretics, ACE inhibitors or ARBs, and calcium channel blockers—selection depends on patient characteristics: 2, 3

• For Black patients: Start with a calcium channel blocker or thiazide diuretic, as ACE inhibitors/ARBs are less effective as monotherapy in this population 2, 5
• For non-Black patients: Any of the three first-line classes is appropriate, though ACE inhibitors/ARBs are often preferred initially 2, 3
• For patients with diabetes or chronic kidney disease with albuminuria: Prioritize ACE inhibitor or ARB 1, 2
• For patients with heart failure: Use ACE inhibitor or ARB plus appropriate additional agents 1, 2
• For patients with coronary artery disease: ACE inhibitor or ARB combined with calcium channel blocker is particularly 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 benefit 2, 3
• ACE inhibitors: Lisinopril 10-40 mg daily or enalapril; note that lisinopril demonstrates superior blood pressure reduction compared to hydrochlorothiazide in predominantly Caucasian populations 5, 3
• ARBs: Candesartan, losartan, or olmesartan if ACE inhibitor not tolerated 2, 3
• Calcium channel blockers: Amlodipine 5-10 mg daily is the preferred dihydropyridine 2, 3

Combination Therapy Algorithm

Two-Drug Combinations

If blood pressure remains uncontrolled on monotherapy, add a second agent from a different class: 2, 6

• ACE inhibitor/ARB + calcium channel blocker: Provides complementary vasodilation and renin-angiotensin system blockade, particularly effective for patients with diabetes, chronic kidney disease, or coronary disease 2
• ACE inhibitor/ARB + thiazide diuretic: Effective combination, especially for volume-dependent hypertension 2
• Calcium channel blocker + thiazide diuretic: Particularly effective in Black patients and elderly patients 2

Three-Drug Combinations

If blood pressure remains ≥140/90 mm Hg on two optimally dosed agents, add a third drug to achieve the guideline-recommended triple therapy of ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic: 2, 6

• This combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction 2
• Optimize doses of existing medications before adding the third agent—for example, increase ARB to maximum dose before adding the diuretic 2, 6

Resistant Hypertension (Four-Drug Regimen)

If blood pressure remains uncontrolled on optimized triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent: 2, 6

• Spironolactone provides additional blood pressure reductions of 20-25/10-12 mm Hg when added to triple therapy 2
• Monitor potassium closely when combining spironolactone with ACE inhibitor/ARB, as hyperkalemia risk is significant 2
• Alternative fourth-line agents if spironolactone is contraindicated include amiloride, doxazosin, eplerenone, or beta-blockers 2

Monitoring and Follow-Up

• Monthly follow-up during drug titration until blood pressure is controlled 1
• Achieve target blood pressure within 3 months of initiating or modifying therapy 2, 6
• Check serum potassium and creatinine 2-4 weeks after initiating ACE inhibitor/ARB or diuretic therapy 2
• Reassess blood pressure within 2-4 weeks after any dose adjustment 2, 6
• Once controlled, follow-up every 3-6 months for patients with stage 1 hypertension 1

Critical Pitfalls to Avoid

• Never combine ACE inhibitor with ARB—this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 2, 6
• Do not add a beta-blocker as third-line therapy unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation) 2
• Verify medication adherence before adding agents—non-adherence is the most common cause of apparent treatment resistance 2, 6
• Do not use non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure 2
• Monitor for peripheral edema with amlodipine—this side effect may be attenuated by adding an ACE inhibitor or ARB 2
• Allow 2-4 weeks for full effect of dose adjustments before making further changes 6

Special Populations

• Elderly patients (≥65 years): Target systolic blood pressure <130 mm Hg if tolerated, but individualize based on frailty 2, 6
• Patients with atrial fibrillation: Favor ARBs, which may reduce recurrence 1
• Patients with thoracic aortic disease: Beta-blockers are preferred 1
• Refer to hypertension specialist if blood pressure remains uncontrolled (≥160/100 mm Hg) despite four-drug therapy at optimal doses 2