What is the best initial antihypertensive medication for a patient with stage 2 hypertension (systolic blood pressure of 160 mmHg)?

Initial Antihypertensive Medication for Stage 2 Hypertension (160/80 mmHg)

For a patient with a systolic blood pressure of 160/80 mmHg, you should immediately initiate two-drug combination therapy, preferably with a thiazide-like diuretic (chlorthalidone preferred over hydrochlorothiazide) plus either an ACE inhibitor, ARB, or dihydropyridine calcium channel blocker, ideally as a single-pill combination. 1

Why Two Drugs Initially

• At 160/80 mmHg, this patient has stage 2 hypertension, which is 30 mmHg above the systolic target of <130 mmHg 2, 1
• When blood pressure is more than 20 mmHg above systolic goal or 10 mmHg above diastolic goal, initiating two antihypertensive agents from different classes is recommended 2
• Single-drug therapy is insufficient for most patients with stage 2 hypertension to achieve blood pressure control 1
• Starting with combination therapy achieves blood pressure goals more rapidly and reduces cardiovascular events sooner 2

Preferred Drug Combinations

For Non-Black Patients:

• First choice: Thiazide-like diuretic (chlorthalidone 12.5-25 mg) + ACE inhibitor (e.g., lisinopril 10-20 mg) 2, 1
• Alternative: Thiazide-like diuretic + ARB (if ACE inhibitor not tolerated) 2, 1
• Alternative: Thiazide-like diuretic + dihydropyridine calcium channel blocker (e.g., amlodipine 5-10 mg) 2, 1

For Black Patients:

• First choice: Thiazide-like diuretic + dihydropyridine calcium channel blocker 2, 1
• ACE inhibitors and ARBs are less effective at lowering blood pressure in Black patients when used as monotherapy 2

Why Chlorthalidone Over Hydrochlorothiazide

• Chlorthalidone is the preferred thiazide-like diuretic over hydrochlorothiazide because it lowers blood pressure more effectively, particularly at night, and has a longer therapeutic half-life 2
• Chlorthalidone and indapamide have more cardiovascular disease risk reduction data than hydrochlorothiazide 2
• Most major hypertension trials demonstrating mortality benefit used chlorthalidone, not hydrochlorothiazide 2

Single-Pill Combinations

• Single-pill combination formulations are strongly preferred to improve medication adherence and simplify the regimen 1
• Fixed-dose combinations produce greater blood pressure reduction at lower doses of component agents, resulting in fewer side effects 2

Blood Pressure Target and Timeline

• Target blood pressure is <130/80 mmHg for most adults 2, 1, 3
• Aim to reduce blood pressure by at least 20/10 mmHg from baseline 1
• Reassess within 1 month after initiating therapy to evaluate response 1
• Achieve target blood pressure within 3 months of treatment initiation 1

Titration Strategy

• If blood pressure target is not achieved within 1 month, increase to full doses of the initial two-drug combination 1
• If blood pressure remains uncontrolled with two drugs at full doses, escalate to a three-drug combination (typically adding the third class not yet used: thiazide + ACE inhibitor/ARB + calcium channel blocker) 1

Special Considerations

If Diabetes Present:

• ACE inhibitors or ARBs are recommended as first-line therapy in combination with a thiazide-like diuretic or calcium channel blocker 2
• These agents provide additional renal protection in diabetic patients with albuminuria 2

If Coronary Artery Disease Present:

• ACE inhibitors or ARBs are recommended first-line in combination with other agents 2

If Chronic Kidney Disease Present:

• ACE inhibitors or ARBs should be included in the regimen, particularly if albuminuria is present 2

Common Pitfalls to Avoid

• Do not start with monotherapy at this blood pressure level—it will delay achieving control and prolong cardiovascular risk 1
• Do not use beta-blockers as first-line therapy unless there is a compelling indication (prior MI, heart failure, or active angina), as they have not been shown to reduce mortality as blood pressure-lowering agents alone 2
• Avoid immediate-release nifedipine for blood pressure lowering—use long-acting dihydropyridine calcium channel blockers instead 4
• Do not use hydrochlorothiazide preferentially—chlorthalidone or indapamide are superior choices 2

Concurrent Lifestyle Modifications

• Implement evidence-based lifestyle interventions immediately alongside pharmacotherapy 1
• Dietary sodium restriction to <2,300 mg/day with increased potassium intake 1, 3
• DASH or Mediterranean diet pattern 2, 3
• Weight reduction if BMI >25 kg/m² 1, 3
• 150 minutes/week of moderate-intensity aerobic exercise 1, 3
• Alcohol limitation and tobacco cessation 3