First‑Line Pharmacologic Management of Hypertension

General First‑Line Options (Uncomplicated Hypertension)

• The Canadian Cardiovascular Society (CCS) recommends thiazide or thiazide‑like diuretics, long‑acting dihydropyridine calcium‑channel blockers (CCBs), ACE inhibitors (for non‑Black patients), or angiotensin‑receptor blockers (ARBs) as first‑line agents, with the choice guided by age, race, and clinical characteristics. 1
• Thiazide‑like diuretics (chlorthalidone or indapamide) are preferred over hydrochlorothiazide because they provide superior cardiovascular protection (Grade A evidence). 5
• Long‑acting dihydropyridine CCBs such as amlodipine or extended‑release nifedipine are appropriate first‑line agents (Grade B evidence). 1
• ACE inhibitors are first‑line in non‑Black patients (Grade B) but should be avoided as initial monotherapy in Black patients (Grade A). 1
• ARBs are acceptable first‑line therapy (Grade B). 1
• β‑blockers are recommended only for patients younger than 60 years; they are not first‑line in patients ≥ 60 years (Grade A). 7

Race‑Specific First‑Line Strategies

• Black patients: Initiate therapy with an ARB + CCB combination or a CCB + thiazide‑like diuretic combination (Grade A). ACE inhibitors alone are not recommended (Grade A). 3
• Non‑Black patients: Begin with a low‑dose ACE inhibitor or ARB, add a CCB if needed, and then add a thiazide‑like diuretic (stepwise approach, Grade A). 3

Isolated Systolic Hypertension

• Preferred first‑line agents are thiazide‑like diuretics (Grade A), long‑acting dihydropyridine CCBs (Grade A), and ARBs (Grade B). 4

Combination Therapy When Monotherapy Fails

• If blood pressure remains uncontrolled on standard‑dose monotherapy, add a second agent from a different class (Grade B). 1
• Preferred combination regimens:
  
  • Thiazide‑like diuretic + CCB (Grade B)
  • CCB + ACE inhibitor (Grade C)
• Avoid ACE inhibitor + ARB combination (Grade A – no additional benefit and higher adverse‑event risk). 7
• Use caution when combining a non‑dihydropyridine CCB with a β‑blocker (Grade D). 1

Resistant Hypertension (Uncontrolled on ≥ 3 Agents)

• Spironolactone is the preferred fourth‑line agent, showing a greater SBP reduction than doxazosin or bisoprolol (Grade A). 5
• Serum potassium must be monitored closely, especially when estimated glomerular filtration rate is < 45 mL/min/1.73 m². 5

Special Populations

Coronary Artery Disease

• ACE inhibitor or ARB is the preferred agent (Grade A).
• β‑blockers are indicated for stable angina (Grade B).
• CCBs may be used (Grade B) but short‑acting nifedipine should be avoided (Grade D). 10

Diabetes

• Without albuminuria:
  
  • ACE inhibitor (Grade A for age ≥ 55 y; Grade B < 55 y) or ARB (Grade A with LVH and age ≥ 55 y).
  • Dihydropyridine CCB or thiazide‑like diuretic (Grade A for age ≥ 55 y).
  • α‑blockers are not recommended (Grade A). 11
• With albuminuria: ACE inhibitor or ARB is required (Grade A). 11

Elderly (≥ 80 y)

• Initiate with monotherapy; the systolic BP threshold to start treatment is 160 mmHg (Grade C).
• Exercise caution with combination therapy to avoid excessive BP reductions. 1

Medications to Avoid or Use With Caution

• α‑blockers are not recommended as first‑line therapy for uncomplicated hypertension (Grade A). 4
• β‑blockers are not first‑line in patients ≥ 60 y (Grade A). 7
• ACE inhibitors are not first‑line in Black patients (Grade A). 1
• NSAIDs and decongestants should be reviewed and discontinued when possible because they raise BP and diminish antihypertensive efficacy (Grade B). 5

Critical Pitfalls

• Do not combine ACE inhibitor with ARB (Grade A – increased adverse effects without benefit). 7
• Monitor for hypokalemia with thiazide monotherapy and supplement potassium as needed (Grade C). 1
• Short‑acting nifedipine should be avoided in patients with coronary disease (Grade D). 10
• In resistant hypertension, screen for secondary causes (primary aldosteronism, obstructive sleep apnea, renal disease, renovascular disease). 5
• Replace thiazide‑type diuretics with thiazide‑like agents for better cardiovascular protection in resistant hypertension (Grade A). 5