First-Line Drugs for Hypertension and Diagnostic Criteria
Diagnostic Criteria for Hypertension
Hypertension is diagnosed when blood pressure is ≥130/80 mm Hg based on the 2017 ACC/AHA guidelines, which replaced the older ≥140/90 mm Hg threshold. 1
Blood Pressure Classification:
- Normal: <120/80 mm Hg 1
- Elevated: 120-129/<80 mm Hg 1
- Stage 1 Hypertension: 130-139/80-89 mm Hg 1
- Stage 2 Hypertension: ≥140/90 mm Hg 1
Treatment Initiation Thresholds:
- Stage 1 hypertension: Initiate pharmacotherapy at BP ≥130/80 mm Hg, particularly in patients with established cardiovascular disease, diabetes, chronic kidney disease, or 10-year ASCVD risk ≥10% 1
- Stage 2 hypertension: Initiate pharmacotherapy at BP ≥140/90 mm Hg in all patients 1
First-Line Antihypertensive Medications
Thiazide or thiazide-like diuretics (particularly chlorthalidone) are the optimal first-line choice for most adults with hypertension, based on the strongest evidence for reducing cardiovascular mortality, stroke, and heart failure. 1, 2, 3
Primary First-Line Drug Classes (in order of preference):
1. Thiazide/Thiazide-like Diuretics (PREFERRED)
- Chlorthalidone 12.5-25 mg once daily is superior to other agents based on the ALLHAT trial, showing better outcomes than ACE inhibitors for stroke prevention and better than calcium channel blockers for heart failure prevention 1, 2, 3
- Hydrochlorothiazide 12.5-25 mg once daily (maximum 50 mg daily) is an acceptable alternative but less potent than chlorthalidone 3, 4
- Thiazide diuretics reduce all-cause mortality by 2-3 deaths per 100 patients treated over 4-5 years 5
- Common pitfall: Monitor potassium levels and maintain >3.5 mmol/L to avoid ventricular ectopy 3
2. Calcium Channel Blockers (CCBs)
- Long-acting dihydropyridines (amlodipine 5-10 mg once daily) are equally effective as thiazides for all cardiovascular events except heart failure 1, 2
- CCBs are the preferred alternative when thiazides are not tolerated 1, 2
- Particularly effective for isolated systolic hypertension in older adults 2
3. ACE Inhibitors
- Lisinopril 10-40 mg once daily or enalapril are effective first-line options 1, 6
- ACE inhibitors reduce all-cause mortality similar to thiazides 5
- Mandatory first-line choice for patients with albuminuria or established coronary artery disease 1, 7
- Monitor: Check serum creatinine, eGFR, and potassium within 7-14 days after initiation 3, 7
4. Angiotensin Receptor Blockers (ARBs)
- Losartan 50-100 mg once daily or candesartan are equally effective to ACE inhibitors 1, 8, 4
- Better tolerated than ACE inhibitors due to lower incidence of cough 2, 9
- Mandatory first-line choice for patients with albuminuria when ACE inhibitors are not tolerated 1, 7
Treatment Algorithm by Clinical Scenario
For Most Adults Without Comorbidities:
- Start with chlorthalidone 12.5-25 mg once daily 1, 2, 3
- If not tolerated, switch to amlodipine 5-10 mg once daily 2, 3
For Black Patients (without heart failure or CKD):
- Start with thiazide diuretic OR calcium channel blocker 1, 3, 7
- Avoid ACE inhibitors/ARBs as monotherapy - they are significantly less effective than thiazides and CCBs for stroke and heart failure prevention in this population 1, 3, 7
For Patients with Diabetes:
- All four first-line classes are equally effective 1
- Consider ACE inhibitor or ARB if albuminuria is present 1, 7
- Target BP <130/80 mm Hg 1
For Patients with Chronic Kidney Disease or Albuminuria:
For Patients with Established Coronary Artery Disease:
- ACE inhibitor or ARB is the preferred first-line choice 7, 10
- Add beta-blocker if history of myocardial infarction 10
Monotherapy vs. Combination Therapy Strategy
Stage 1 Hypertension (130-139/80-89 mm Hg):
- Start with single-agent therapy, titrate dosage, then add sequential agents if needed to reach target <130/80 mm Hg 1, 3, 7
Stage 2 Hypertension (≥140/90 mm Hg or >20/10 mm Hg above target):
- Start with two first-line agents from different classes, preferably as a single-pill combination 1, 3
- Effective combinations: ACE inhibitor/ARB + CCB, ACE inhibitor/ARB + thiazide, or CCB + thiazide 2, 7
- Caution in older patients: Use combination therapy carefully due to increased risk of hypotension and orthostatic hypotension 1
Medications to AVOID as First-Line
Beta-Blockers:
- NOT recommended as first-line therapy unless specific comorbidities exist (prior MI, active angina, heart failure with reduced ejection fraction) 1, 2, 3
- Beta-blockers are 36% less effective than CCBs and 30% less effective than thiazides for stroke prevention 1, 3
- Associated with 44% increased risk of composite cardiovascular outcomes compared to thiazides 11
Alpha-Blockers:
- NOT used as first-line therapy - less effective for cardiovascular disease prevention than thiazides 1, 3
Combination of ACE Inhibitor + ARB:
- Never combine ACE inhibitors with ARBs - increases adverse effects without additional benefit 7
Target Blood Pressure Goals
- General population: <140/90 mm Hg (strong recommendation) 1
- Patients with known CVD: <130/80 mm Hg (strong recommendation) 1
- High-risk patients (diabetes, CKD, high CVD risk): Consider <130/80 mm Hg (conditional recommendation) 1
- Adults ≥65 years: SBP <130 mm Hg if tolerated 4
Follow-Up and Monitoring
- Monthly reassessment after medication initiation or changes until target BP achieved 1, 7
- Every 3-5 months once blood pressure is controlled 1, 7
- Monitor electrolytes and renal function within 7-14 days when starting ACE inhibitors, ARBs, or diuretics, then at least annually 3, 7
- Check standing BP in elderly patients to assess for orthostatic hypotension 2
Critical Pitfalls to Avoid
- Don't use beta-blockers as first-line unless compelling indications exist 1, 2, 3
- Don't combine ACE inhibitors with ARBs 7
- Don't ignore standing BP measurements in elderly patients 2
- Don't use rapid dose escalation in older adults - increases adverse effects 2
- Don't use ACE inhibitors or ARBs as monotherapy in Black patients without specific indications 1, 3, 7