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Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design.

Abstract

BACKGROUND

Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-converting-enzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin I and angiotensin II levels, may thereby provide greater benefit compared to ACEi or ARB alone.

METHODS

The primary objective of the ALTITUDE trial is to determine whether aliskiren 300 mg once daily, reduces cardiovascular and renal morbidity and mortality compared with placebo when added to conventional treatment (including ACEi or ARB). ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged > or =35 years): those with either urinary albumin/creatinine ratio (UACR) > or =200 mg/g; microalbuminuria (UACR) > or =20 <200 mg/g and eGFR > or =30 <60 mL/min/1.73 m2; and thirdly, those with a history of cardiovascular disease and eGFR > or =30 <60 mL/min/1.73 m2 with or without microalbuminuria. ALTITUDE is an event driven trial that aims to randomize 8600 patients with a planned follow-up time of 48 months. The primary outcome measure is time to first event for the composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease or doubling of baseline serum creatinine concentration. Secondary endpoints include a composite CV endpoint and a composite renal endpoint.

CONCLUSION

ALTITUDE will determine whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. hhparving@dadlnet.dk

    , , , , , , , , , ,

    Source

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Amides
    Angiotensin II Type 1 Receptor Blockers
    Angiotensin-Converting Enzyme Inhibitors
    Antihypertensive Agents
    Cardiovascular Diseases
    Diabetes Mellitus, Type 2
    Dose-Response Relationship, Drug
    Double-Blind Method
    Endpoint Determination
    Female
    Fumarates
    Glomerular Filtration Rate
    Humans
    Kidney Diseases
    Male
    Middle Aged
    Outcome Assessment (Health Care)
    Renin-Angiotensin System
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    19145003

    Citation

    Parving, Hans-Henrik, et al. "Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): Rationale and Study Design." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 24, no. 5, 2009, pp. 1663-71.
    Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant. 2009;24(5):1663-71.
    Parving, H. H., Brenner, B. M., McMurray, J. J., de Zeeuw, D., Haffner, S. M., Solomon, S. D., ... Pfeffer, M. A. (2009). Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 24(5), pp. 1663-71. doi:10.1093/ndt/gfn721.
    Parving HH, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): Rationale and Study Design. Nephrol Dial Transplant. 2009;24(5):1663-71. PubMed PMID: 19145003.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. AU - Parving,Hans-Henrik, AU - Brenner,Barry M, AU - McMurray,John J V, AU - de Zeeuw,Dick, AU - Haffner,Steven M, AU - Solomon,Scott D, AU - Chaturvedi,Nish, AU - Ghadanfar,Mathieu, AU - Weissbach,Nicole, AU - Xiang,Zhihua, AU - Armbrecht,Juergen, AU - Pfeffer,Marc A, Y1 - 2009/01/14/ PY - 2009/1/16/entrez PY - 2009/1/16/pubmed PY - 2009/8/4/medline SP - 1663 EP - 71 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 24 IS - 5 N2 - BACKGROUND: Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-converting-enzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin I and angiotensin II levels, may thereby provide greater benefit compared to ACEi or ARB alone. METHODS: The primary objective of the ALTITUDE trial is to determine whether aliskiren 300 mg once daily, reduces cardiovascular and renal morbidity and mortality compared with placebo when added to conventional treatment (including ACEi or ARB). ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged > or =35 years): those with either urinary albumin/creatinine ratio (UACR) > or =200 mg/g; microalbuminuria (UACR) > or =20 <200 mg/g and eGFR > or =30 <60 mL/min/1.73 m2; and thirdly, those with a history of cardiovascular disease and eGFR > or =30 <60 mL/min/1.73 m2 with or without microalbuminuria. ALTITUDE is an event driven trial that aims to randomize 8600 patients with a planned follow-up time of 48 months. The primary outcome measure is time to first event for the composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospitalization for heart failure, onset of end-stage renal disease or doubling of baseline serum creatinine concentration. Secondary endpoints include a composite CV endpoint and a composite renal endpoint. CONCLUSION: ALTITUDE will determine whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/19145003/Aliskiren_Trial_in_Type_2_Diabetes_Using_Cardio_Renal_Endpoints__ALTITUDE_:_rationale_and_study_design_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfn721 DB - PRIME DP - Unbound Medicine ER -