ACE inhibitors vs. ARBs vs. DRIssystematic review update
Online Appendices
Appendix Table A. Types and Sources of Grey Literature Searched
Type of source / Specific sources searchedRegulatory information / FDA
Health Canada
Authorized Medicines for EU
Clinical trial registries / ClinicalTrials.gov
Current Controlled Trials
Clinical Study Results
WHO Clinical Trials
Abstracts and conference papers / Conference Papers Index
Scopus
Grants and federally funded research / NIH RePORTER (a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other research institutions)
HSRPROJ (a database providing access to ongoing grants and contracts in health services research)
Other miscellaneous sources / Hayes, Inc. Health Technology Assessment
NY Academy of Medicine’s Grey Literature Index
Abbreviations: EU = European Union; FDA = U.S. Food and Drug Administration; NIH = National Institutes of Health; NY = New York; WHO = World Health Organization.
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ACE inhibitors vs. ARBs vs. DRIssystematic review update
Appendix Table B. Data Abstraction Form
Study / Interventions andstudy design / Patient
characteristics / Results / Comments/
quality/applicability
StudyID / Geographical location: [city & state (U.S.) or city & country (foreign)]
Study dates: [month & year]
Funding source:
Interventions:
[For each treatment arm, describe drug, dose (incl. titration protocol), and number of patients randomized]
Were additional anti-hypertension medications allowed: [Delete all but one]
Yes/No/ NR = not reported
If Yes to above, was this done: [delete all but one]
Per protocol
At discretion of clinician/investigator
NR
Study design:
[Delete all but one]
RCT, parallel-group
RCT, crossover
Other [specify]
Blinding:
[For each item, Yes/No/NR]
- Patients:
- Providers:
- Assessors of outcomes:
Was allocation concealment adequate? [e.g., computer-generated list or central randomization]
Yes/No/NR
Baseline/run-in period: [length & intervention, or NA = not applicable]
Washout period(s): [crossover trials only; length]
Duration of treatment: [post-baseline/run-in; days, weeks, months]
Duration of post-treatment followup: [days, weeks, months, or NA = not applicable] / Number of patients:
- Screened for inclusion:
- Eligible for inclusion:
- Randomized:
- Began treatment:
- Completed treatment:
- Withdrawals/losses to followup:
Age:
Mean (SD):
Median:
Range:
Sex (n [%]):
Female:
Male:
Race/ethnicity (n [%]):
Baseline blood pressure:
[by treatment group, if given; indicate how assessed]
Concurrent non-hypertension medications (n [%]):
Comorbidities (n [%]):
Recruitment setting:
[Inclusion/exclusion criteria: describe these as reported in article. If tolerability was assessed during run-in or used as an incl/excl criterion, please note this.]
Inclusion criteria:
Exclusion criteria: / [Where necessary, specify how outcomes were defined and assessed. Report quantitative data and p-values, where available; give N’s for specific outcomes if these differ from N’s randomized; give time point(s) for abstracted data and note other time points available in the article. Include any results reported separately for subgroups of patients based on demographic characteristics (age, racial and ethnic groups, sex), use of other medications concurrently, or co-morbidities.]
1) Blood pressure:
[Prefer seated trough BP, if reported; if BP outcomes other than the one(s) you abstract are reported, list these]
2) Rate of use of a single antihypertensive agent for BP control:
3) Mortality:
[all-cause, cardiovascular disease-specific, and cerebrovascular disease-specific]
4) Morbidity:
[cardiac events (MI), heart failure, cerebral vascular disease or events (incl. stroke), symptomatic coronary artery disease, end-stage renal disease, PVD, quality of life]
5) Safety:
[overall adverse events (AEs), withdrawals due to AEs, serious AEs reported, switch rates]
6) Specific adverse events:
[including, but not limited to: weight gain, impaired renal function, hyperkalemia, angioedema, cough]:
7) Persistence/adherence:
8) Lipid levels:
9) Progression to type 2 diabetes:
10) Markers of carbohydrate metabolism/diabetes control:
[HbA1c, insulin or other diabetes med dosage, fasting plasma glucose, aggregated measures of serial glucose measurements]
11) LV mass/function:
12) Creatinine/GFR:
13) Proteinuria: / [IF ARTICLE SHOULD BE EXCLUDED, PLEASE EXPLAIN WHY HERE]
General comments:
[Comment here on biases, etc., affecting clinical interpretation]
Quality assessment:
[Assign an overall quality rating of “Good,” “Fair,” or “Poor” based on the definitions provided in the guidance sheet. If study is rated as “Fair” or “Poor,” note important limitations in internal validity (see guidance sheet assessing quality) under “Comments”, below.]
Overall rating:
Comments:
Applicability:
[List the most important (up to 3) limitations affecting applicability, if any, based on the list given in the guidance sheet on assessing applicability.]
This article is relevant to: [Delete as appropriate]
Question 1
Question 2
Question 3
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ACE inhibitors vs. ARBs vs. DRIssystematic review update
Appendix Figure 1. Successful blood pressure control on monotherapy: estimate of summary effect over time.
Angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs). The x-axis represents the publication year of the included studies, with the number of studies evaluating successful monotherapy as an outcome immediately below the x-axis. The left y-axis indicates the cumulative number of patients included in the studies by year; these results are shown by the gray solid line. The right y-axis indicates the cumulative summary estimate (black square) and the 95% CI (line) for the included studies over time.
Appendix Figure 2. Cough as an adverse event: estimate of summary effect over time.
Angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs). The x-axis represents the publication year of the included studies, with the number of studies evaluating cough as an adverse event immediately below the x-axis. The left y-axis indicates the cumulative number of patients included in the studies by year; these results are shown by the gray solid line. The right y-axis indicates the cumulative summary estimate (black square) and the 95% CI (line) for the included studies over time.
Appendix Figure 3. Withdrawals due to adverse events: estimate of summary effect over time.
Angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs). The x-axis represents the publication year of the included studies, with the number of studies evaluating withdrawals due to adverse events immediately below the x-axis. The left y-axis indicates the cumulative number of patients included in the studies by year; these results are shown by the gray solid line. The right y-axis indicates the cumulative summary estimate (black square) and the 95% CI (line) for the included studies over time.
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ACE inhibitors vs. ARBs vs. DRIssystematic review update
Appendix Table C. Number of Studies (Number of Publications) that Evaluated Various Treatment Comparisons
ARBs / DRI / TotalsUnspecified “ARBs” / Candesartan cilexetil / Eprosartan / Irbesartan / Losartan / Olmesartan medoxomil / Telmisartan / Valsartan / Aliskiren
ACE inhibitors / Unspecified “ACE inhibitors” / 20 (22) / 1 (1) / 0 / 2 (2) / 2 (2) / 0 / 0 / 0 / 0 / 25 (27)
Benazepril / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 1 (1) / 0 / 1 (1)
Captopril / 0 / 0 / 0 / 0 / 2 (2) / 0 / 0 / 0 / 0 / 2 (2)
Enalapril / 0 / 4 (4) / 2 (6) / 4 (4) / 13 (15) / 0 / 5 (5) / 2 (2) / 0 / 30 (36)
Fosinopril / 0 / 0 / 0 / 2 (2) / 1 (1) / 0 / 0 / 0 / 0 / 3 (3)
Lisinopril / 0 / 6 (6) / 0 / 0 / 0 / 0 / 3 (3) / 5 (5) / 0 / 14 (14)
Moexipril / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
Perindopril / 0 / 1 (1) / 0 / 0 / 2 (2) / 0 / 3 (3) / 0 / 0 / 6 (6)
Quinapril / 0 / 0 / 0 / 2 (2) / 3 (3) / 0 / 0 / 0 / 0 / 5 (5)
Ramipril / 0 / 0 / 0 / 0 / 2 (2) / 1 (1) / 5 (5) / 3 (3) / 2 (3) / 13 (14)
Trandolapril / 0 / 0 / 0 / 0 / 1 (1) / 0 / 0 / 0 / 0 / 1 (1)
DRI / Aliskiren / 0 / 0 / 0 / 0 / 1 (1) / 0 / 0 / 0 / - / 1 (1)
Totals / 19 (21) / 12 (12) / 2 (6) / 10 (10) / 27 (29) / 0 / 16 (16) / 11 (11) / 2 (3) / -
Abbreviations: ACE inhibitors = angiotensin-converting enzyme; ARBs = angiotensin II receptor blockers/antagonists; DRI = direct renin inhibitor.
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ACE inhibitors vs. ARBs vs. DRIssystematic review update
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