What is the recommended first‑line antihypertensive for uncomplicated primary hypertension, and is exercise safe while taking it?

First-Line Blood Pressure Medication for Uncomplicated Hypertension

For uncomplicated primary hypertension, thiazide-type diuretics—specifically chlorthalidone 12.5-25 mg daily—are the most strongly recommended first-line medication, and exercise is not only safe but actively encouraged while taking any standard blood pressure medication. 1, 2

Recommended First-Line Medication

Thiazide-type diuretics are the gold standard for initial treatment based on the strongest evidence for reducing cardiovascular mortality, stroke, and heart failure compared to all other antihypertensive drug classes. 1, 2

Specific Drug Choice Within Thiazides

• Chlorthalidone 12.5-25 mg once daily is preferred over hydrochlorothiazide because it was used in the landmark cardiovascular outcome trials and provides superior 24-hour blood pressure control, particularly overnight blood pressure reduction. 1, 2
• Chlorthalidone at 25 mg is more potent than hydrochlorothiazide 50 mg and has a longer half-life (40-60 hours), allowing once-daily dosing with sustained effect. 2, 3
• Hydrochlorothiazide 12.5-25 mg daily remains an acceptable alternative if chlorthalidone is not available or tolerated. 2

Alternative First-Line Options

If thiazide diuretics are contraindicated or not tolerated, the following are acceptable alternatives for uncomplicated hypertension:

• ACE inhibitors (angiotensin-converting enzyme inhibitors) 1, 2
• ARBs (angiotensin receptor blockers) 1, 2
• Calcium channel blockers (CCBs), particularly long-acting dihydropyridines like amlodipine 1, 2

However, these alternatives have weaker outcome data than thiazides for preventing heart failure. Network meta-analyses show thiazides significantly outperform calcium channel blockers for heart failure prevention and demonstrate trends toward better stroke and cardiovascular event prevention compared to ACE inhibitors. 1

Treatment Initiation Strategy

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

• Start with a single agent (monotherapy with a thiazide diuretic). 2, 4
• Titrate the dose upward before adding a second medication. 2
• Target blood pressure is <130/80 mmHg. 1, 2

For Stage 2 Hypertension (≥160/100 mmHg or >20/10 mmHg above target)

• Initiate with two first-line agents simultaneously from different drug classes, either as separate pills or fixed-dose combination. 1, 2
• Typical combinations include thiazide + ACE inhibitor, thiazide + ARB, or thiazide + calcium channel blocker. 1

Special Population Considerations

For Black patients without heart failure or chronic kidney disease:

• Start with a thiazide diuretic OR calcium channel blocker rather than an ACE inhibitor or ARB alone. 1, 2
• ACE inhibitors are 30-36% less effective than thiazides and calcium channel blockers for preventing stroke and heart failure in Black patients. 2

Medications to Avoid as First-Line

Beta-blockers should NOT be used as first-line therapy for uncomplicated hypertension because they are significantly less effective than other drug classes, particularly for stroke prevention (36% less effective than calcium channel blockers, 30% less effective than thiazides). 2, 4

Alpha-blockers are NOT recommended as first-line therapy due to inferior cardiovascular disease prevention compared to thiazides. 2

Exercise Safety While Taking Blood Pressure Medications

Exercise is completely safe and strongly recommended while taking any standard first-line antihypertensive medication, including thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers. 1

Exercise as Part of Treatment

• Lifestyle modifications including regular exercise are mandatory components of hypertension management and should be implemented alongside medication therapy. 1
• Exercise provides additional blood pressure reduction beyond medication alone and improves overall cardiovascular risk. 1
• No restrictions on exercise are needed for patients taking thiazide diuretics, ACE inhibitors, ARBs, or calcium channel blockers. 1

Monitoring Considerations During Exercise

• Maintain adequate hydration when exercising on thiazide diuretics to prevent excessive volume depletion. 3
• Monitor for orthostatic symptoms (lightheadedness upon standing) when starting medication, particularly in older adults, but this does not contraindicate exercise. 5
• Potassium levels should be monitored within 7-14 days after starting thiazide diuretics and maintained >3.5 mmol/L. 2

Common Pitfalls to Avoid

Do not use combination pills (like amlodipine/benazepril) as initial first-line therapy for stage 1 hypertension—these are reserved for patients who fail monotherapy or have stage 2 hypertension requiring dual therapy from the start. 5

Do not combine ACE inhibitors with ARBs—dual renin-angiotensin system blockade increases adverse events without added cardiovascular benefit. 1, 5

Do not withhold thiazide diuretics due to concerns about metabolic effects (glucose, uric acid)—the cardiovascular benefits far outweigh these risks, and metabolic abnormalities can be managed if they occur. 3

Do not use loop diuretics (like furosemide) as first-line therapy—they have no outcome data for hypertension treatment and should be reserved for heart failure or advanced kidney disease. 3

Monitoring Timeline

• Reassess blood pressure 2-4 weeks after starting medication to evaluate response before dose adjustment. 5
• Achieve target blood pressure within 3 months of treatment initiation. 5
• Once at target, monitor blood pressure every 3-6 months. 5
• Check electrolytes and kidney function within 7-14 days after starting thiazides, ACE inhibitors, or ARBs. 2