Telmisartan, ramipril, or both in patients at high risk for vascular events
Open accessAbstract
BACKGROUND: In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS: After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS: Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).
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Two clinical trials studied the combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the medication combination had higher adverse event rates (hyperkalemia and/or AKI).
“Two clinical trials studied the combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the medication combination had higher adverse event rates (hyperkalemia and/or AKI) (87,88).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [87]
The Discussion reports that telmisartan plus ramipril provided no significant benefit on the cardiovascular primary outcome and increased hyperkalemia and renal dysfunction. The paper reports renal harm, but does not establish the claim that the combination provided no benefit on CKD outcomes; its stated prevention outcome was vascular events. This citation supports the ONTARGET trial's findings, not the findings of both trials cited in the sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTwo clinical trials studied combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the medication combination had higher adverse event rates (hyperkalemia and/or AKI).
“Two clinical trials studied the combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the medication combination had higher adverse event rates (hyperkalemia and/or AKI) (95,96).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [95]
The Discussion (page unavailable) reports that adding telmisartan to ramipril gave no significant benefit for the primary cardiovascular outcome and increased renal dysfunction and hyperkalemia. This paper is one trial, not both trials cited in the sentence. It does not establish a lack of benefit for CKD specifically, and it reports renal dysfunction rather than explicitly identifying acute kidney injury. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events-namely, hyperkalemia, syncope, and AKI.
“inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events-namely, hyperkalemia, syncope, and AKI (78)(79)(80).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [78]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable, 1 not checked. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events-namely, hyperkalemia, syncope, and AKI.
“However, the use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events—namely, hyperkalemia, syncope, and AKI (74–76).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [74]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe combination of an ACE inhibitor and an angiotensin receptor blocker is associated with a consistent increase in serious side effects.
“The combination of an ACE inhibitor and an angiotensin receptor blocker is associated with a consistent increase in serious side effects.431”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [431]
Combining ACE inhibitors and ARBs, or combining an ACE inhibitor or ARB with a direct renin inhibitor, lacks added ASCVD benefit and increases hyperkalemia, syncope, and acute kidney injury.
“However, the use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD bene fi t and increased rate of adverse events -namely, hyperkalemia, syncope, and acute kidney injury (AKI) (71 -73).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [71]
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11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026
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- Authors
- The ONTARGET Investigators
- Affiliations
- Population Health Research Institute (CA)
- Corresponding author
- The ONTARGET Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-04-10
- Volume
- 358
- Issue
- 15
- Pages
- 1547-1559
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2152798629
- Semantic Scholar
- d0138c63468b530ba14a4e5f56a17d615c8df084
- Cited by
- 3,502
- References
- 27
- Citations by year
- 2026: 50 · 2025: 98 · 2024: 106 · 2023: 112 · 2022: 86 · 2021: 114 · 2020: 110 · 2019: 124 · 2018: 140 · 2017: 162 · 2016: 180 · 2015: 196 · 2014: 235 · 2013: 246 · 2012: 307
- FWCI
- 296.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Bristol-Myers Squibb
- AstraZeneca
- Sanofi
- Heart and Stroke Foundation of Canada
- Novo Nordisk
- Servier
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- telmisartan, ramipril, combination therapy, ACE inhibitors, angiotensin receptor blockers, vascular disease, cardiovascular events, myocardial infarction, stroke, heart failure hospitalization, blood pressure reduction, cough, angioedema, hypotension, adverse drug reactions, cardiovascular mortality, secondary prevention, antihypertensive therapy
- MeSH terms
- Telmisartan, Aged, Angioedema, Angiotensin-Converting Enzyme Inhibitors, Benzimidazoles, Benzoates, Blood Pressure, Cardiovascular Diseases, Creatinine, Diabetes Mellitus, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Hospitalization, Humans, Male, Middle Aged, Risk, Ramipril, Angiotensin II Type 1 Receptor Blockers, Kaplan-Meier Estimate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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