What is the initial management for a patient with uncontrolled hypertension?

Initial Management of Uncontrolled Hypertension

For patients with uncontrolled hypertension (BP ≥140/90 mmHg), initiate both lifestyle modifications and pharmacological treatment immediately, with the choice of single versus dual therapy determined by the absolute BP level and cardiovascular risk stratification. 1

Risk Stratification Determines Treatment Intensity

Before selecting medications, stratify patients by total cardiovascular risk—not BP level alone—as this determines whether to start with monotherapy or combination therapy. 1 Patients with high or very high cardiovascular risk (diabetes, established CVD, chronic kidney disease, or multiple risk factors) should initiate combination therapy immediately, even at BP levels of 140-159/90-99 mmHg. 1

Pharmacological Treatment Algorithm

For BP 140-159/90-99 mmHg:

• Start with single-drug therapy if the patient has low-to-moderate cardiovascular risk, though combination therapy is preferred even at this level. 1
• Start with two-drug combination therapy if the patient has high or very high cardiovascular risk (diabetes, established CVD, CKD, or multiple risk factors). 1

For BP ≥160/100 mmHg:

• Always initiate treatment with two antihypertensive medications from the start, preferably as a single-pill combination to improve adherence. 1

First-Line Medication Classes

Select from these four major drug classes: 1, 2

• Thiazide or thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide)
• ACE inhibitors (e.g., lisinopril 10 mg once daily initially) 3
• Angiotensin receptor blockers (ARBs)
• Long-acting dihydropyridine calcium channel blockers (e.g., amlodipine)

Preferred Two-Drug Combinations

When initiating dual therapy, use these effective and well-tolerated combinations: 1, 2

• Thiazide diuretic + ACE inhibitor
• Thiazide diuretic + ARB
• Calcium channel blocker + ACE inhibitor
• Calcium channel blocker + ARB

Strongly prefer single-pill combinations over separate pills to improve medication adherence. 1

Special Population Considerations

Black Patients:

• Initial treatment should include a diuretic or calcium channel blocker, either alone or in combination with a RAS blocker (ACE inhibitor or ARB). 1, 4

Patients with Diabetes and Albuminuria:

• Mandatory first-line therapy is an ACE inhibitor or ARB, regardless of BP level. 1, 4

Patients with Heart Failure with Reduced Ejection Fraction:

• Treatment must include an ACE inhibitor (or ARB), beta-blocker, and diuretic/MRA if required. 1

Patients with Chronic Kidney Disease:

• Target systolic BP of 120-139 mmHg, with RAS blockers recommended when albuminuria is present. 1

Patients with Metabolic Syndrome or High Diabetes Risk:

• Avoid the thiazide + beta-blocker combination due to dysmetabolic effects. 1

Target Blood Pressure Goals

• <140/90 mmHg for most patients without comorbidities 2, 4
• <130/80 mmHg for patients with established CVD, diabetes, CKD, or high cardiovascular risk 1, 4
• <130 mmHg systolic for patients with known cardiovascular disease 2, 4

Lifestyle Modifications (Concurrent with Medications)

Implement all of the following simultaneously: 1, 2

• Sodium restriction to <1500 mg/day or reduction of at least 1000 mg/day
• Increased potassium intake (3500-5000 mg/day)
• Weight loss if overweight/obese
• Physical activity: aerobic or dynamic resistance exercise 90-150 minutes per week
• Alcohol moderation: ≤2 drinks per day in men, ≤1 per day in women
• DASH-like diet rich in fruits, vegetables, whole grains, and low-fat dairy products

Monitoring and Follow-Up

• Monthly visits until BP target is achieved 1
• Home BP monitoring or ambulatory BP monitoring to confirm diagnosis and monitor treatment effectiveness 1
• Monitor serum creatinine/eGFR and potassium at least annually for patients on ACE inhibitors, ARBs, or diuretics 1, 4
• After BP control is achieved, follow-up every 3-5 months 4

Critical Pitfalls to Avoid

• Never use sequential monotherapy as the default approach—it is laborious, frustrating, and delays BP control in high-risk patients. 1
• Never combine ACE inhibitors with ARBs due to lack of additional benefit and increased risk of hyperkalemia, syncope, and acute kidney injury. 4
• Never combine ACE inhibitors or ARBs with direct renin inhibitors. 4
• Avoid rapid BP lowering in asymptomatic patients and assess for white coat hypertension. 1
• Address medication adherence proactively, as poor compliance is the most common cause of resistant hypertension. 1

Management of Resistant Hypertension

If BP remains uncontrolled on three medications (including a diuretic at optimal doses): 1, 5

• Reinforce lifestyle measures, especially sodium restriction
• Add spironolactone at low dose as a fourth agent (most effective add-on therapy)
• Exclude secondary causes: obstructive sleep apnea, renal artery stenosis, primary aldosteronism, and medication non-adherence
• Consider alternatives to spironolactone: amiloride, doxazosin, eplerenone, or other antihypertensive classes not yet used 5