Korean Circ J.  2020 Jan;50(1):52-68. 10.4070/kcj.2019.0173.

Comparison of First-Line Dual Combination Treatments in Hypertension: Real-World Evidence from Multinational Heterogeneous Cohorts

• You SC
• Jung S
• Swerdel JN
• Ryan PB
• Schuemie M
• Suchard MA
• Lee S
• Cho J
• Hripcsak G
• Park RW
• Park S

• KMID: 2465664
• DOI: http://doi.org/10.4070/kcj.2019.0173

Abstract

BACKGROUND AND OBJECTIVES
2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D).
METHODS
Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure.
RESULTS
A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97−1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87−1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95−1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01−1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01−1.17; p=0.040) than A+D.
CONCLUSIONS
There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice.

Keyword

Hypertension; Antihypertensive agents; Angiotensin receptor antagonists; Calcium channel blockers; Diuretics

MeSH Terms

Adult
Angiotensin Receptor Antagonists
Antihypertensive Agents
Calcium Channel Blockers
Calcium Channels
Cardiovascular Diseases
Cohort Studies*
Diuretics
Heart Failure
Humans
Hypertension*
Korea
Mortality
Myocardial Infarction
Propensity Score
Stroke
Angiotensin Receptor Antagonists
Antihypertensive Agents
Calcium Channel Blockers
Calcium Channels
Diuretics

Figure

• 

  Figure 1 Kaplan-Meier plots for overall survival comparing different dual combination treatments in propensity score-matched cohorts from each data source. (A) CEDM, (B) CCAE, (C) Medicare, (D) Medicaid, and (E) NHIS-NSC. A = angiotensin converting enzyme inhibitors/angiotensin-receptor blockers; C = calcium-channel blocker; CCAE = Truven MarketScan Commercial Claims and Encounters; CEDM = OptumInsight's Clinformatics™ Data Mart; D = thiazide diuretics; Medicaid = Truven MarketScan Multi-State Medicaid; Medicare = Truven MarketScan Medicare Supplemental Beneficiaries; NHIS-NSC = National Health Insurance Service-National Sample Cohort.

• 

  Figure 2 Forest plots depicting HR and 95% CI for primary outcome in each data source. The overall HRs were calculated using a random-effects model. The size of data markers indicates the weight of the study. Error bars indicate 95% CIs. (A) A+C vs. A+D, (B) C+D vs. A+C, and (C) C+D vs. A+D. A = angiotensin converting enzyme inhibitors/angiotensin-receptor blockers; C = calcium-channel blocker; CCAE = Truven MarketScan Commercial Claims and Encounters; CEDM = OptumInsight's Clinformatics™ Data Mart; CI = confidential interval; D = thiazide diuretics; HR = hazard ratio; Medicaid = Truven MarketScan Multi-State Medicaid; Medicare = Truven MarketScan Medicare Supplemental Beneficiaries; NHIS-NSC = National Health Insurance Service-National Sample Cohort. *Event rate per 1,000 person-year.

• 

  Figure 3 Forest plots depicting HR and 95% CI for secondary outcomes in each data source. The overall HRs were calculated using a random-effects model. The size of data markers indicates the weight of the study. Error bars indicate 95% CIs. (A) Myocardial infarction, (B) Heart failure, (C) Stroke, and (D) MACCE. A = angiotensin converting enzyme inhibitors/angiotensin-receptor blockers; C = calcium-channel blocker; CCAE = Truven MarketScan Commercial Claims and Encounters; CEDM = OptumInsight's Clinformatics™ Data Mart; CI = confidential interval; D = thiazide diuretics; HR = hazard ratio; MACCE = major adverse cardiac and cerebrovascular event; Medicaid = Truven MarketScan Multi-State Medicaid; Medicare = Truven MarketScan Medicare Supplemental Beneficiaries; NHIS-NSC = National Health Insurance Service-National Sample Cohort. *Event rate per 1,000 person-year.

• 

  Figure 4 Forest plots depicting HR and 95% CI for primary outcome in subgroups. The overall HRs were calculated using a random-effects model. The size of data markers indicates the weight of the study. Error bars indicate 95% CIs. (A) Women, (B) Men, (C) ≥60 years, (D) <60 years. A = angiotensin converting enzyme inhibitors/angiotensin-receptor blockers; C = calcium-channel blocker; CCAE = Truven MarketScan Commercial Claims and Encounters; CEDM = OptumInsight's Clinformatics™ Data Mart; CI = confidential interval; D = thiazide diuretics; HR = hazard ratio; MACCE = major adverse cardiac and cerebrovascular event; Medicaid = Truven MarketScan Multi-State Medicaid; Medicare = Truven MarketScan Medicare Supplemental Beneficiaries; NHIS-NSC = National Health Insurance Service-National Sample Cohort. *Event rate per 1,000 person-year.

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