Tags

Type your tag names separated by a space and hit enter

Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies.

Abstract

BACKGROUND

In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria.

METHODS AND RESULTS

Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (P = 0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44).

CONCLUSIONS

This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately.

CLINICAL TRIAL REGISTRATION

URL: http://clinicaltrials.gov Identifier: NCT00153101.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. sheldon.tobe@sunnybrook.ca

    , , , , , , , ,

    Source

    Circulation 123:10 2011 Mar 15 pg 1098-107

    MeSH

    Aged
    Albuminuria
    Angiotensin Receptor Antagonists
    Angiotensin-Converting Enzyme Inhibitors
    Benzimidazoles
    Benzoates
    Creatinine
    Drug Therapy, Combination
    Female
    Glomerular Filtration Rate
    Heart Failure
    Heart Rate
    Humans
    Kidney Failure, Chronic
    Male
    Middle Aged
    Myocardial Infarction
    Ramipril
    Stroke
    Telmisartan
    Treatment Outcome

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21357827

    Citation

    Tobe, Sheldon W., et al. "Cardiovascular and Renal Outcomes With Telmisartan, Ramipril, or Both in People at High Renal Risk: Results From the ONTARGET and TRANSCEND Studies." Circulation, vol. 123, no. 10, 2011, pp. 1098-107.
    Tobe SW, Clase CM, Gao P, et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation. 2011;123(10):1098-107.
    Tobe, S. W., Clase, C. M., Gao, P., McQueen, M., Grosshennig, A., Wang, X., ... Mann, J. F. (2011). Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation, 123(10), pp. 1098-107. doi:10.1161/CIRCULATIONAHA.110.964171.
    Tobe SW, et al. Cardiovascular and Renal Outcomes With Telmisartan, Ramipril, or Both in People at High Renal Risk: Results From the ONTARGET and TRANSCEND Studies. Circulation. 2011 Mar 15;123(10):1098-107. PubMed PMID: 21357827.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. AU - Tobe,Sheldon W, AU - Clase,Catherine M, AU - Gao,Peggy, AU - McQueen,Matthew, AU - Grosshennig,Anja, AU - Wang,Xingyu, AU - Teo,Koon K, AU - Yusuf,Salim, AU - Mann,Johannes F E, AU - ,, Y1 - 2011/02/28/ PY - 2011/3/2/entrez PY - 2011/3/2/pubmed PY - 2011/6/3/medline SP - 1098 EP - 107 JF - Circulation JO - Circulation VL - 123 IS - 10 N2 - BACKGROUND: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria. METHODS AND RESULTS: Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (P = 0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44). CONCLUSIONS: This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov Identifier: NCT00153101. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/21357827/Cardiovascular_and_renal_outcomes_with_telmisartan_ramipril_or_both_in_people_at_high_renal_risk:_results_from_the_ONTARGET_and_TRANSCEND_studies_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.110.964171?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -