What is a good starting treatment for hypertension in a 50-year-old male with no significant comorbidities or contraindications?

Initial Antihypertensive Treatment for a 50-Year-Old Male

Start with dual combination therapy using an ACE inhibitor (or ARB) plus either a thiazide diuretic or a calcium channel blocker, rather than monotherapy. 1, 2

Rationale for Dual Therapy from the Start

• The European Society of Cardiology (2025) explicitly recommends starting immediately with two-drug combination therapy rather than monotherapy for confirmed hypertension (BP ≥140/90 mmHg). 1
• When BP is ≥20/10 mmHg above goal, initiating two medications increases the likelihood of achieving BP control within 3 months and reduces cardiovascular morbidity and mortality more effectively than sequential monotherapy. 2
• Most patients with hypertension will require at least two blood pressure lowering drugs to achieve recommended goals. 3

Specific First-Line Combination Options

Option 1 (Preferred for most patients): ACE inhibitor + Calcium Channel Blocker

• Example: Lisinopril 10 mg + Amlodipine 5 mg once daily 2, 4
• This combination provides complementary mechanisms—vasodilation through calcium channel blockade and renin-angiotensin system inhibition. 5

Option 2 (Alternative): ACE inhibitor + Thiazide Diuretic

• Example: Lisinopril 10 mg + Chlorthalidone 12.5 mg once daily 2
• Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and proven cardiovascular disease reduction in trials. 5
• The efficacy of chlorthalidone is supported by the highest-level evidence from three comparative clinical trials in more than 50,000 patients. 6

Option 3 (For Black patients): Calcium Channel Blocker + Thiazide Diuretic

• For Black patients, the combination of a calcium channel blocker plus a thiazide diuretic may be more effective than calcium channel blocker plus an ACE inhibitor/ARB. 5

Single-Pill Combinations

• Fixed-dose single-pill combinations are recommended when available to improve adherence. 1, 2
• When no disadvantages of cost exist, fixed drug combinations are recommended. 3

Blood Pressure Targets and Timeline

• Target BP: <130/80 mmHg (or at minimum <140/90 mmHg if unable to tolerate lower targets). 2, 7
• Aim to achieve target within 3 months of initiating therapy, with at least a 20/10 mmHg reduction from baseline. 2
• Start both medications at low doses initially and reassess BP in 2-4 weeks after initiation. 2

Titration Strategy

• If BP goal not achieved at 2-4 weeks, increase to full doses of both medications before adding a third agent. 2
• Maximum doses: Lisinopril up to 40 mg daily 4, Amlodipine up to 10 mg daily, Chlorthalidone up to 25 mg daily. 5

Essential Concurrent Lifestyle Modifications

• Sodium restriction to <2g/day by eliminating excessively salty foods and limiting salt in cooking. 1
• Weight reduction to achieve BMI 20-25 kg/m² through reduced fat and total calorie intake. 1
• Regular aerobic physical activity (90-150 minutes/week of predominantly dynamic exercise like brisk walking). 1, 2
• Alcohol limitation to <21 units/week for men. 1
• Adopt a DASH diet rich in fruits, vegetables, whole grains, and low-fat dairy. 2

Critical Pitfalls to Avoid

• Never start with monotherapy alone for confirmed hypertension (BP ≥140/90 mmHg)—combination therapy is recommended from the outset. 1
• Never combine two renin-angiotensin system inhibitors (ACE inhibitor + ARB) as this increases risk of hyperkalemia, syncope, and acute kidney injury without additional cardiovascular benefit. 2, 5
• Never delay pharmacological treatment while attempting lifestyle modifications alone—both should be initiated simultaneously. 1

Monitoring Plan

• Follow-up in 2-4 weeks after medication initiation to assess BP response and adverse effects. 2
• Implement home BP monitoring (target <135/85 mmHg) to confirm office readings. 1, 2
• Monitor serum potassium and creatinine 2-4 weeks after initiating ACE inhibitors or diuretics. 1

If Blood Pressure Remains Uncontrolled on Dual Therapy

• Add a third agent from the remaining class (thiazide diuretic if started with ACE inhibitor + calcium channel blocker, or calcium channel blocker if started with ACE inhibitor + thiazide). 5
• The combination of ACE inhibitor + calcium channel blocker + thiazide diuretic represents guideline-recommended triple therapy. 5, 2