What are the recommended combination therapies for hypertension in black patients in Canada?

Recommended Combination Therapies for Hypertension in Black Patients in Canada

For black patients with hypertension in Canada, initial treatment should be with a 2-drug combination comprising a thiazide-type diuretic and calcium channel blocker (CCB), or a CCB with an angiotensin receptor blocker (ARB). 1

First-Line Combination Therapy Options

Preferred Initial Combinations for Black Patients:

1. Thiazide/thiazide-like diuretic + Dihydropyridine CCB

   • Example: Chlorthalidone + Amlodipine
   • Rationale: This combination provides complementary mechanisms of action and has demonstrated superior efficacy in black patients 1, 2

2. Dihydropyridine CCB + ARB

   • Example: Amlodipine + Valsartan
   • Rationale: Studies show this combination achieves greater and quicker BP reductions in black patients with stage 2 hypertension compared to monotherapy 3

Treatment Algorithm for Black Patients

Step 1: Initial Therapy

• Start with low-dose ARB + dihydropyridine CCB or dihydropyridine CCB + thiazide/thiazide-like diuretic 1
• Preferably use single-pill combinations to improve adherence 1

Step 2: Dose Optimization

• If BP remains uncontrolled, increase to full doses of initial medications 1

Step 3: Triple Therapy

• If BP still uncontrolled, add the third agent (diuretic or ARB/ACEI) 1
• Note: ACE inhibitors are less effective as monotherapy in black patients but can be effective in combination regimens 4

Step 4: Resistant Hypertension

• Add spironolactone or, if not tolerated/contraindicated, consider amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 1

Evidence-Based Considerations

Racial Differences in Treatment Response:

• Black patients typically show better response to CCBs and diuretics than to ACE inhibitors or ARBs when used as monotherapy 2, 4
• The ALLHAT study demonstrated that thiazide-type diuretics were more effective than ACE inhibitors in black patients for preventing stroke and combined cardiovascular disease outcomes 2

Combination vs. Monotherapy:

• The EX-STAND study showed that initiating with amlodipine/valsartan combination achieved greater BP reductions and higher control rates than amlodipine monotherapy in black patients with stage 2 hypertension 3
• A recent meta-analysis supports CCB + ACEI rather than hydrochlorothiazide + ACEI as first-line combination therapy in patients of African ancestry 5

Common Pitfalls and Caveats

1. Avoid monotherapy initiation in most black patients with hypertension, especially those with stage 2 hypertension (≥160/100 mmHg) 1

2. Beta-blockers as initial therapy should generally be avoided in black patients unless there are specific indications (e.g., coronary artery disease) 5

3. ACE inhibitor monotherapy is less effective in black patients and should not be used as first-line therapy without a CCB or diuretic 2, 4

4. Monitor for adverse effects:

   • Hypokalemia and hyperglycemia with CCB + diuretic combinations
   • Hyperkalemia with ARB/ACEI combinations, especially in patients with kidney disease 5

5. Target BP should be <130/80 mmHg for most patients, but individualize for elderly patients based on frailty 1

By following this evidence-based approach to combination antihypertensive therapy in black patients, clinicians can achieve better blood pressure control and potentially improve cardiovascular outcomes in this population.