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Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.

Abstract

BACKGROUND

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.

METHODS

The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.

FINDINGS

784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.

INTERPRETATION

In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

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  • Authors+Show Affiliations

    ,

    Schwabing General Hospital, and KfH Kidney Centre, Ludwig Maximilians University Munchen, Germany.

    , , , , , , , , , , , , , , , , , ,

    Source

    Lancet (London, England) 372:9638 2008 Aug 16 pg 547-53

    MeSH

    Aged
    Angiotensin II Type 1 Receptor Blockers
    Angiotensin-Converting Enzyme Inhibitors
    Benzimidazoles
    Benzoates
    Cardiovascular Diseases
    Creatinine
    Diabetes Mellitus
    Double-Blind Method
    Drug Therapy, Combination
    Follow-Up Studies
    Glomerular Filtration Rate
    Humans
    Kidney
    Middle Aged
    Proteinuria
    Ramipril
    Telmisartan

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18707986

    Citation

    Mann, Johannes F E., et al. "Renal Outcomes With Telmisartan, Ramipril, or Both, in People at High Vascular Risk (the ONTARGET Study): a Multicentre, Randomised, Double-blind, Controlled Trial." Lancet (London, England), vol. 372, no. 9638, 2008, pp. 547-53.
    Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547-53.
    Mann, J. F., Schmieder, R. E., McQueen, M., Dyal, L., Schumacher, H., Pogue, J., ... Yusuf, S. (2008). Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet (London, England), 372(9638), pp. 547-53. doi:10.1016/S0140-6736(08)61236-2.
    Mann JF, et al. Renal Outcomes With Telmisartan, Ramipril, or Both, in People at High Vascular Risk (the ONTARGET Study): a Multicentre, Randomised, Double-blind, Controlled Trial. Lancet. 2008 Aug 16;372(9638):547-53. PubMed PMID: 18707986.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. AU - Mann,Johannes F E, AU - Schmieder,Roland E, AU - McQueen,Matthew, AU - Dyal,Leanne, AU - Schumacher,Helmut, AU - Pogue,Janice, AU - Wang,Xingyu, AU - Maggioni,Aldo, AU - Budaj,Andrzej, AU - Chaithiraphan,Suphachai, AU - Dickstein,Kenneth, AU - Keltai,Matyas, AU - Metsärinne,Kaj, AU - Oto,Ali, AU - Parkhomenko,Alexander, AU - Piegas,Leopoldo S, AU - Svendsen,Tage L, AU - Teo,Koon K, AU - Yusuf,Salim, AU - ,, PY - 2008/8/19/pubmed PY - 2008/8/30/medline PY - 2008/8/19/entrez SP - 547 EP - 53 JF - Lancet (London, England) JO - Lancet VL - 372 IS - 9638 N2 - BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS: The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION: In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/18707986/Renal_outcomes_with_telmisartan_ramipril_or_both_in_people_at_high_vascular_risk__the_ONTARGET_study_:_a_multicentre_randomised_double_blind_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61236-2 DB - PRIME DP - Unbound Medicine ER -