Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

doi:10.1161/HYPERTENSIONAHA.120.16667

Comparative Study

. 2021 Sep;78(3):591-603.

doi: 10.1161/HYPERTENSIONAHA.120.16667. Epub 2021 Jul 26.

Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

RuiJun Chen^{1

2}, Marc A Suchard^{3

4}, Harlan M Krumholz^{5

6}, Martijn J Schuemie^{3

7}, Steven Shea⁸, Jon Duke⁹, Nicole Pratt¹⁰, Christian G Reich¹¹, David Madigan¹², Seng Chan You¹³, Patrick B Ryan¹, George Hripcsak^{1

14}

Affiliations

¹ Department of Biomedical Informatics, Columbia University Irving Medical Center, New York (R.C., P.B.R., G.H.).
² Department of Translational Data Science and Informatics, Geisinger, Danville, PA (R.C.).
³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (M.A.S., M.J.S.).
⁴ Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (M.A.S.).
⁵ Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT (H.M.K.).
⁶ Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, CT (H.M.K.).
⁷ Epidemiology Analytics, Janssen Research and Development, Titusville, NJ (M.J.S.).
⁸ Department of Medicine (S.S.), Columbia University, New York.
⁹ Georgia Tech Research Institute, Georgia Tech College of Computing, Atlanta (J.D.).
¹⁰ Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia (N.P.).
¹¹ Real World Solutions, IQVIA, Cambridge, MA (C.G.R.).
¹² Department of Statistics (D.M.), Columbia University, New York.
¹³ Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea (S.C.Y.).
¹⁴ Medical Informatics Services, New York-Presbyterian Hospital (G.H.).

PMID: 34304580
PMCID: PMC8363588
DOI: 10.1161/HYPERTENSIONAHA.120.16667

Comparative Study

Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

RuiJun Chen et al. Hypertension. 2021 Sep.

. 2021 Sep;78(3):591-603.

doi: 10.1161/HYPERTENSIONAHA.120.16667. Epub 2021 Jul 26.

Authors

Affiliations

¹ Department of Biomedical Informatics, Columbia University Irving Medical Center, New York (R.C., P.B.R., G.H.).
² Department of Translational Data Science and Informatics, Geisinger, Danville, PA (R.C.).
³ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (M.A.S., M.J.S.).
⁴ Department of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (M.A.S.).
⁵ Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT (H.M.K.).
⁶ Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, CT (H.M.K.).
⁷ Epidemiology Analytics, Janssen Research and Development, Titusville, NJ (M.J.S.).
⁸ Department of Medicine (S.S.), Columbia University, New York.
⁹ Georgia Tech Research Institute, Georgia Tech College of Computing, Atlanta (J.D.).
¹⁰ Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia (N.P.).
¹¹ Real World Solutions, IQVIA, Cambridge, MA (C.G.R.).
¹² Department of Statistics (D.M.), Columbia University, New York.
¹³ Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea (S.C.Y.).
¹⁴ Medical Informatics Services, New York-Presbyterian Hospital (G.H.).

PMID: 34304580
PMCID: PMC8363588
DOI: 10.1161/HYPERTENSIONAHA.120.16667

Abstract

[Figure: see text].

Keywords: angiotensin receptor; angiotensin receptor blocker; cardiovascular outcomes; hypertension; safety.

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Figures

**Figure 1.. Covariate balance before and after propensity score stratification across all databases.**
Each point represents the standardized difference of means for a single covariate before and after large-scale propensity score stratification in new users of ACE inhibitors and ARBs. All databases achieved covariate balance, defined as a standardized difference of the mean ≤ 0.1, except for the NHIS/NSC database.

**Figure 2.. Preference score distributions across all databases.**
Distribution of preference scores, a transformation of propensity score adjusting for differences in prevalence, in new users of ACE inhibitors (red) as compared to ARBs (purple). Greater overlap indicates that patients in the target and comparator populations are more similar in their likelihood of receiving the target treatment. We achieve clinical empirical equipoise in all comparisons except for the NHIS/NSC database.

**Figure 3:. Risk of cardiovascular outcomes in ACE-inhibitors vs ARBs across all databases.**
Forest plot of hazard ratios and 95% Cis for primary outcomes of acute myocardial infarction (MI), heart failure, stroke, and composite cardiovascular events (CVE) across all databases and meta-analyses. Meta-analysis 2 excludes the NHIS/NSC database while ‘Meta-analysis’ includes all databases.

See this image and copyright information in PMC

Comment in

Why Are We Still Prescribing Angiotensin-Converting Enzyme Inhibitors?
Messerli FH, Bavishi C, Bangalore S. Messerli FH, et al. Circulation. 2022 Feb 8;145(6):413-415. doi: 10.1161/CIRCULATIONAHA.121.057835. Epub 2022 Feb 7. Circulation. 2022. PMID: 35130055 No abstract available.

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References

1. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Himmelfarb CD, et al.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology 2018;71:e127–e248. doi:10.1016/j.jacc.2017.11.006. - DOI - PubMed
1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al.2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021–3104. doi:10.1093/eurheartj/ehy339. - DOI - PubMed
1. Reboussin David M, Allen Norrina B, Griswold Michael E, Eliseo Guallar, Yuling Hong, Lackland Daniel T., et al.Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;71:e116–e135. doi:10.1161/HYP.0000000000000067. - DOI - PubMed
1. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. New England Journal of Medicine 2000;342:145–153. doi:10.1056/NEJM200001203420301. - DOI - PubMed
1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–2997. doi:10.1001/jama.288.23.2981. - DOI - PubMed

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[1] Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Himmelfarb CD, et al.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology 2018;71:e127–e248. doi:10.1016/j.jacc.2017.11.006. - DOI - PubMed

[2] Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Himmelfarb CD, et al.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology 2018;71:e127–e248. doi:10.1016/j.jacc.2017.11.006. - DOI - PubMed

[3] Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al.2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021–3104. doi:10.1093/eurheartj/ehy339. - DOI - PubMed

[4] Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al.2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021–3104. doi:10.1093/eurheartj/ehy339. - DOI - PubMed

[5] Reboussin David M, Allen Norrina B, Griswold Michael E, Eliseo Guallar, Yuling Hong, Lackland Daniel T., et al.Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;71:e116–e135. doi:10.1161/HYP.0000000000000067. - DOI - PubMed

[6] Reboussin David M, Allen Norrina B, Griswold Michael E, Eliseo Guallar, Yuling Hong, Lackland Daniel T., et al.Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;71:e116–e135. doi:10.1161/HYP.0000000000000067. - DOI - PubMed

[7] The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. New England Journal of Medicine 2000;342:145–153. doi:10.1056/NEJM200001203420301. - DOI - PubMed

[8] The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. New England Journal of Medicine 2000;342:145–153. doi:10.1056/NEJM200001203420301. - DOI - PubMed

[9] ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–2997. doi:10.1001/jama.288.23.2981. - DOI - PubMed

[10] ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–2997. doi:10.1001/jama.288.23.2981. - DOI - PubMed

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Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

Affiliations

Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study

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