First-Line Antihypertensive Therapy for a 57-Year-Old Overweight Male with Newly Diagnosed Hypertension

Direct Recommendation

Start chlorthalidone 12.5–25 mg once daily as first-line therapy, or hydrochlorothiazide 25 mg once daily if chlorthalidone is unavailable. 1, 2

Thiazide and thiazide-like diuretics are recommended as one of four acceptable first-line drug therapies by the ACC/AHA guidelines, with chlorthalidone preferred over hydrochlorothiazide due to superior 24-hour blood pressure control and stronger cardiovascular outcomes data. 1
Chlorthalidone has been compared directly to hydrochlorothiazide and lowers blood pressure more effectively, particularly at night, with a much longer therapeutic half-life (24–72 hours vs 6–12 hours). 1
Both chlorthalidone and indapamide have more cardiovascular disease risk reduction data than hydrochlorothiazide, making thiazide-like diuretics the preferred choice even in non-resistant hypertension. 1
In the landmark ALLHAT trial involving over 42,000 patients, chlorthalidone was superior to the ACE inhibitor lisinopril in preventing stroke and superior to the calcium channel blocker amlodipine in preventing heart failure. 1, 3
Thiazide diuretics are the only class of antihypertensives that has been shown to reduce risk of cardiovascular events in patients with isolated systolic hypertension, which is particularly relevant for this patient's age group. 4

Start chlorthalidone at 12.5 mg once daily in the morning, with the option to increase to 25 mg daily if blood pressure remains uncontrolled after 4 weeks. 1, 2
If chlorthalidone is unavailable, start hydrochlorothiazide 25 mg once daily. 1, 2
Low-dose thiazide therapy (12.5–25 mg chlorthalidone or 25 mg hydrochlorothiazide) is well-tolerated with minimal biochemical adverse effects and does not adversely affect quality of life. 5, 4

If a thiazide diuretic cannot be used due to contraindications (e.g., gout, severe hypokalemia) or intolerance, an ACE inhibitor (lisinopril 10 mg daily) or ARB (losartan 50 mg daily) is the next best choice. 2, 3
Calcium channel blockers (amlodipine 5 mg daily) are also acceptable first-line agents, particularly effective in older patients and Black patients. 1, 2
The ACC/AHA guideline recommends thiazide diuretics, ACE inhibitors/ARBs, and calcium channel blockers as equally acceptable first-line therapies in patients without selected comorbidities. 1, 2

Target blood pressure is <130/80 mmHg for most adults under 65 years, based on the 2017 ACC/AHA guidelines. 1, 2
Reassess blood pressure within 2–4 weeks after initiating therapy, with the goal of achieving target blood pressure within 3 months. 1
Check serum potassium and creatinine 2–4 weeks after initiating diuretic therapy to detect potential hypokalemia or changes in renal function. 1
Confirm the diagnosis of hypertension with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) if not already done. 1

If blood pressure remains ≥140/90 mmHg after 4 weeks on optimal-dose monotherapy, add a second agent from a different class rather than continuing to uptitrate the first drug. 1, 2
The preferred two-drug combinations are: (1) thiazide diuretic + ACE inhibitor/ARB, (2) thiazide diuretic + calcium channel blocker, or (3) ACE inhibitor/ARB + calcium channel blocker. 1, 2
Combination therapy is more effective than monotherapy dose escalation for achieving blood pressure control and should be initiated early if blood pressure is significantly elevated (≥160/100 mmHg). 1

Sodium restriction to <2 g/day provides a 5–10 mmHg systolic reduction and enhances the efficacy of all antihypertensive classes, especially diuretics. 1, 2
Weight loss is particularly important for this overweight patient—losing approximately 10 kg reduces blood pressure by about 6.0/4.6 mmHg (systolic/diastolic). 1
The DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat) lowers blood pressure by approximately 11.4/5.5 mmHg. 1
Regular aerobic exercise (≥30 minutes most days, approximately 150 minutes/week moderate intensity) reduces blood pressure by approximately 4/3 mmHg. 1
Limit alcohol intake to ≤2 drinks/day for men, as excess consumption interferes with blood pressure control. 1

Do not start with a beta-blocker as first-line therapy in this patient without compelling indications (e.g., coronary artery disease, heart failure, post-myocardial infarction), as beta-blockers are less effective than diuretics for stroke prevention and cardiovascular events. 1
Do not delay treatment intensification if blood pressure remains uncontrolled—prompt action within 2–4 weeks is required to reduce cardiovascular risk. 1
Do not assume treatment failure without first confirming medication adherence, as non-adherence is the most common cause of apparent treatment resistance. 1
Do not combine an ACE inhibitor with an ARB (dual renin-angiotensin system blockade), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1
Avoid high-dose thiazide diuretics (>25 mg chlorthalidone or >50 mg hydrochlorothiazide), as they increase metabolic side effects without proportional blood pressure benefit. 5, 4

Being overweight is a modifiable risk factor that significantly contributes to hypertension—emphasize weight loss as a cornerstone of therapy alongside medication. 1, 2
At age 57, this patient is at moderate cardiovascular risk and will benefit significantly from early, aggressive blood pressure control to prevent future stroke, myocardial infarction, and heart failure. 1, 2
Thiazide diuretics may cause mild hyperglycemia and increase diabetes risk, but this does not reduce their efficacy in preventing cardiovascular events and should not preclude their use in overweight patients. 5, 3