What is the first line treatment for a newly diagnosed adult patient with hypertension (HTN) and no significant comorbidities?

First-Line Treatment for Hypertension

For newly diagnosed adults with hypertension and no significant comorbidities, initiate treatment with one of four first-line drug classes: thiazide or thiazide-like diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), or long-acting dihydropyridine calcium channel blockers, combined with lifestyle modifications. 1, 2

Treatment Algorithm Based on Blood Pressure Stage and Risk

Stage 1 Hypertension (130-139/80-89 mmHg)

• Low cardiovascular risk (<10% 10-year ASCVD risk): Start with lifestyle modifications alone for 3-6 months before considering pharmacotherapy 1
• High cardiovascular risk (≥10% 10-year ASCVD risk): Initiate both lifestyle modifications AND single-agent pharmacotherapy immediately 1

Stage 2 Hypertension (≥140/90 mmHg)

• Initiate combination therapy with two agents from different first-line classes immediately, preferably as a single-pill combination to improve adherence 1, 2
• Combine lifestyle modifications with pharmacotherapy 1

Hypertensive Crisis (≥180/110 mmHg)

• Begin prompt antihypertensive drug treatment within one week, with rapidity dependent on presence of target organ damage 1

First-Line Pharmacologic Agent Selection

The WHO provides strong recommendation (high-quality evidence) for any of these four classes 1, 2:

1. Thiazide or thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide)
2. ACE inhibitors (e.g., lisinopril, enalapril)
3. Angiotensin receptor blockers (ARBs) (e.g., candesartan, losartan)
4. Long-acting dihydropyridine calcium channel blockers (e.g., amlodipine)

Among these options, thiazide diuretics (particularly chlorthalidone) may provide optimal first-step therapy based on meta-analyses and large randomized controlled trials. 2, 3

Special Population Considerations

• Black patients without heart failure or CKD: Prefer thiazide diuretic or calcium channel blocker as initial therapy 2
• Patients with diabetes, CKD, or proteinuria: Prefer ACE inhibitor or ARB as initial agent 2, 4
• Pregnant or potentially pregnant women: ACE inhibitors and ARBs are absolutely contraindicated due to fetal toxicity 4

Blood Pressure Targets

• Standard target: <140/90 mmHg for all patients without comorbidities 1, 2
• Intensive target: <130/80 mmHg for adults <65 years 2, 3
• Patients with known CVD: <130 mmHg systolic (strong recommendation) 1, 2
• High-risk patients (diabetes, CKD, high CVD risk): Consider <130 mmHg systolic 1, 2

Essential Lifestyle Modifications

All patients should implement these non-pharmacological interventions 1, 3:

• Dietary sodium restriction: <1500 mg/day or reduce by at least 1000 mg/day 4, 3
• Increased potassium intake: 3500-5000 mg/day through diet 4, 3
• DASH diet: Emphasize fruits, vegetables, whole grains, low-fat dairy products 4, 3, 5
• Weight loss: Achieve BMI 18.5-24.9 kg/m² and waist circumference <102 cm (men) or <88 cm (women) 3, 6
• Physical activity: 30-60 minutes of aerobic exercise 4-7 days per week 3, 6
• Alcohol moderation: ≤14 drinks/week (men) or ≤9 drinks/week (women) 4, 3, 6

The DASH diet alone produces blood pressure reduction equivalent to single-drug therapy and should be emphasized as the most effective dietary intervention. 7, 5

Monitoring Schedule

• Monthly follow-up after initiating or changing medications until target BP achieved 1, 2
• Every 3-5 months once BP is controlled 1, 2
• Monitor renal function and potassium within first 3 months when using ACE inhibitors, ARBs, or diuretics 2

Critical Pitfalls to Avoid

• Never combine ACE inhibitor + ARB + renin inhibitor simultaneously - this is potentially harmful and contraindicated 1
• Do not delay treatment initiation for extensive laboratory testing in stage 2 hypertension; testing should not impede starting therapy 1
• Avoid monotherapy in stage 2 hypertension - these patients require combination therapy from the outset 1, 2
• Do not use ACE inhibitors or ARBs in women of childbearing potential without contraception due to teratogenic effects 4

Combination Therapy Strategy

When single-agent therapy is insufficient 1, 2:

• Add a second agent from a different first-line class with complementary mechanism of action
• Preferred combinations: Diuretic + ACE inhibitor/ARB + calcium channel blocker 2, 3
• Use single-pill combinations when possible to improve adherence and persistence 1, 2

Most patients ultimately require multiple agents for adequate BP control, with typical effective regimens including three-drug combinations from the first-line classes 2, 3.