What are the recommended combination regimens for hypertensive black patients?

Recommended Combination Regimens for Hypertensive Black Patients

For black hypertensive patients, initial antihypertensive treatment should include a thiazide-type diuretic and/or calcium channel blocker (CCB), either alone or in combination with each other, as the foundation of therapy. 1

First-Line Combination Therapy

Preferred Initial Combinations

• Thiazide-type diuretic + CCB (most effective initial combination)
• CCB + ARB (alternative effective combination)

The 2022 ACC/AHA and ESC/ESH harmonized guidelines specifically recommend that initial antihypertensive drug therapy in black patients should include a thiazide-type diuretic or CCB 1. For most black patients requiring combination therapy, a two-drug combination comprising a diuretic and CCB is recommended.

Evidence-Based Rationale

Black hypertensive patients typically have:

• Lower renin levels (low-renin hypertension)
• Reduced response to ACE inhibitor or ARB monotherapy
• Better response to diuretics and CCBs

The ALLHAT study demonstrated that in black patients, thiazide diuretics (chlorthalidone) were more effective in lowering BP and reducing cardiovascular events compared to ACE inhibitors (lisinopril) 2. This study showed that black patients treated with lisinopril had:

• Higher risk of stroke (RR 1.40)
• Higher risk of combined cardiovascular disease (RR 1.19)
• Higher risk of heart failure (RR 1.30)

Stepwise Approach for Black Hypertensive Patients

1. Initial therapy:

   • For mild hypertension: Start with either thiazide-type diuretic or CCB monotherapy
   • For moderate-to-severe hypertension (≥140/90 mmHg): Start with combination of thiazide-type diuretic + CCB 1

2. If BP remains uncontrolled:

   • Add ARB to the diuretic + CCB combination (creating a triple therapy)
   • Consider using single-pill combinations to improve adherence 1

3. For resistant hypertension:

   • Add spironolactone as a fourth agent
   • If spironolactone is not tolerated, consider adding eplerenone, amiloride, doxazosin, or a beta-blocker 1

Important Clinical Considerations

• ACE inhibitors/ARBs as monotherapy: Black patients have a reduced BP response to ACE inhibitor or ARB monotherapy compared to white patients 3. Black patients also have a greater risk of angioedema with ACE inhibitors 1.

• Combination therapy effectiveness: When ACE inhibitors or ARBs are combined with either a diuretic or CCB, the racial differences in BP response are eliminated 3. Studies show that high-dose combinations (such as amlodipine/benazepril 10/40 mg) result in similar BP reductions in both black and white hypertensive patients 4.

• Specific drug selection:

  • For CCBs: Amlodipine is preferred due to once-daily dosing and established efficacy 5
  • For thiazide diuretics: Chlorthalidone or hydrochlorothiazide at adequate doses (12.5-25 mg for chlorthalidone; 25-50 mg for hydrochlorothiazide) 1
  • For ARBs: Losartan may be preferred over ACE inhibitors due to lower risk of angioedema 6

Common Pitfalls to Avoid

1. Monotherapy with ACE inhibitors or ARBs: This approach is less effective in black patients and may lead to inadequate BP control 3.

2. Inadequate diuretic dosing: Lower doses of thiazide diuretics are less effective in clinical outcome trials 1.

3. Ignoring combination therapy benefits: Single-drug approaches often fail to achieve adequate BP control in black patients, who frequently require ≥2 antihypertensive medications 1.

4. Not monitoring for adverse effects: Watch for electrolyte abnormalities with diuretics and peripheral edema with CCBs.

By following these evidence-based recommendations for combination therapy in black hypertensive patients, clinicians can optimize BP control and reduce cardiovascular morbidity and mortality.