Journal Article:

nejmoa1901113

Summary:

Daniel DeMarco                                  Journal Article Assignment         Rotation #9: Family Medicine

Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans

D.B. Ojji, B. Mayosi, et al.

New England Journal of Medicine

Why Was the Study Performed?:

• HTN is common among Black Africans and African Americans
• At the minimum, dual therapy is often necessary to achieve BP control. The most efficacious combination(s) has not yet been elicited
• Recommendations for dual combinations that should be utilized for African American patients differ across three guidelines in the United States
  • Hypothesis: Taken from monotherapy guidelines which suggest that these therapies are more effective than other classes, a calcium-channel blocker plus a thiazide diuretic would produce more effective BP control than either a CCB + ACEI or a Diuretic + ACEI.

How Was the Study Performed?:

• CREOLE Trial (Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans)
• Randomized, single-blind, three-group trial
• N = 728 patients from six countries in sub-Saharan Africa assigned to receive daily regimens, for a period of 2 months and then would receive doubled doses for an additional 4 months, of:
  1. 5mg Amlodipine + 12.5mg HCTZ à 10mg Amlodipine + 25mg HCTZ
  2. 5mg Amlodipine + 4mg Perindopril à 10mg Amlodipine + 8mg Perindopril
  3. 4mg Perindopril + 12.5mg HCTZ à 8mg Perindopril + 25mg HCTZ
• Primary Outcome: Change in 24h ambulatory SBP between baseline and 6mo.
• Secondary Outcomes: Change in ambulatory DBP, change in mean daytime and nighttime ambulatory BP, change in office BP at 2, 4, and 6 months, proportion of patients with controlled office BP, proportion of patients who had a response to treatment, changes in blood analytes, pulse rates, adverse events

What Were the Inclusion Criteria?:

• M/F Black Patients with HTN between ages 30yo-79yo if they had not received previous treatment for HTN and had SBP of 150-179mmHg or if they had a SBP of 140-159mmHg while receiving monotherapy
• Patients were excluded if they had CVD history, secondary hypertension, or were pregnant.

What Were the Results of the Study?:

• 621 (85.3%) patients underwent ambulatory BP monitoring at baseline and at 6mo.
• Primary Outcome: Change in 24h ambulatory SBP between baseline and 6mo.
  • Groups receiving Amlodipine + Perindopril or Amlodipine + HCTZ had greater statistically significant reductions in BP than in the Perindopril + HCTZ group
  • There were no statistically significant differences between SBP reduction in the groups receiving Amlodipine + Perindopril or Amlodipine + HCTZ
• Secondary Outcome: Change in Office BP
  • At 2 months, the group that received Amlodipine + HCTZ had a greater reduction in SBP than the group that received Amlodipine + Perindopril
  • At 4 and 6 months, the between-group differences were negligible

What are the Limitations of the Study?:

• Uncertainty about whether these data apply to black patients with DM or those outside sub-Saharan Africa or if the results pertain to other agents in the same drug classes

What is the Bottom Line?:

• Combination Amlodipine plus either HCTZ or Perindopril were more effective than Perindopril + HCTZ in reducing both ambulatory SBP and office blood pressure

What are the Clinical Implications of These Findings?:

• These results suggest that a calcium-channel blocker (particularly amlodipine) may play a significant role in lower BP among Black African patients as part of the two-drug combinations
• These results contrast recommendations in the most recent US guidelines which advise the use of either a CCB or a diuretic in combination with a different drug class; the results contrast the recommendations of European guidelines, which recommend the use of CCB with a diuretic or with an ACEI or a combination of an ACEI with a diuretic
• When treating African American patients with HTN, the clinician should start with Amlodipine (clinically proven efficacious monotherapy) and should there be a need for dual-therapy, should add either an ACEI or a thiazide diuretic