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The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial.

Abstract

AIMS

In the Ongoing Telmisartan Alone and in Combination with Ramipril Trial (ONTARGET), dual agent renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not reduce the risk of renal and cardiovascular outcomes compared with the single use of either agent. Dual therapy however increased the incidence of hyperkalemia. We examined risk factors for hyper- and hyokalemia and hypothesized that both would be associated with worse cardiovascular and renal outcomes.

METHODS

A post-hoc analysis of the ONTARGET trial comparing dual therapy (ramipril and telmisartan) vs monotherapy (ramipril or telmisartan) was performed. The association between serum potassium at week 6 on cardiovascular and renal outcomes during the 56 months follow-up was assessed by multivariate Cox analysis. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The renal outcome was defined as the composite of a doubling of serum creatinine or chronic dialysis.

RESULTS

Six weeks after randomization, hyperkalemia developed in 210 (2.7%) patients on dual therapy vs. 264 (1.6%) patients on monotherapy (p < 0.001 vs. dual therapy). Hypokalemia developed in 87 (1.1%) patients on dual therapy vs. 200 (1.2%)patients on monotherapy. Serum potassium was nonlinearly associated with cardiovascular and renal events with a nadir between 4.0-5.0 mmol/l for cardiovascular and 4.0-4.5 mmol/l for renal events such that subjects above or below these values exhibited higher risks. This association was independent of age, gender, diabetes, estimated glomerular filtration rate, systolic blood pressure and diuretic use.

CONCLUSIONS

With the precautions stipulated by the protocol of the ONTARGET trial, hypokalemia and hyperkalemia were infrequent events. Nevertheless, both high and low serum potassium were associated with an increased risk of cardiovascular and renal disease.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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    Source

    MeSH

    Aged
    Angiotensin II Type 1 Receptor Blockers
    Angiotensin-Converting Enzyme Inhibitors
    Antihypertensive Agents
    Benzimidazoles
    Benzoates
    Blood Pressure
    Creatinine
    Drug Therapy, Combination
    Female
    Heart Failure
    Hospitalization
    Humans
    Hyperkalemia
    Hypertension
    Hypokalemia
    Kidney
    Kidney Diseases
    Logistic Models
    Male
    Middle Aged
    Multivariate Analysis
    Myocardial Infarction
    Nonlinear Dynamics
    Odds Ratio
    Potassium
    Proportional Hazards Models
    Ramipril
    Renal Dialysis
    Renin-Angiotensin System
    Risk Assessment
    Risk Factors
    Stroke
    Telmisartan
    Time Factors
    Treatment Outcome

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    24191305

    Citation

    Heerspink, Hiddo J Lambers, et al. "The Effect of Ramipril and Telmisartan On Serum Potassium and Its Association With Cardiovascular and Renal Events: Results From the ONTARGET Trial." European Journal of Preventive Cardiology, vol. 21, no. 3, 2014, pp. 299-309.
    Heerspink HJ, Gao P, de Zeeuw D, et al. The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. Eur J Prev Cardiol. 2014;21(3):299-309.
    Heerspink, H. J., Gao, P., de Zeeuw, D., Clase, C., Dagenais, G. R., Sleight, P., ... Mann, J. F. (2014). The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. European Journal of Preventive Cardiology, 21(3), pp. 299-309. doi:10.1177/2047487313510678.
    Heerspink HJ, et al. The Effect of Ramipril and Telmisartan On Serum Potassium and Its Association With Cardiovascular and Renal Events: Results From the ONTARGET Trial. Eur J Prev Cardiol. 2014;21(3):299-309. PubMed PMID: 24191305.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. AU - Heerspink,Hiddo J Lambers, AU - Gao,Peggy, AU - de Zeeuw,Dick, AU - Clase,Catherine, AU - Dagenais,Gilles R, AU - Sleight,Peter, AU - Lonn,Eva, AU - Teo,Koon T, AU - Yusuf,Salim, AU - Mann,Johannes F, Y1 - 2013/11/04/ PY - 2013/11/6/entrez PY - 2013/11/6/pubmed PY - 2014/10/22/medline KW - Dual RAAS blockade KW - cardiovascular KW - hyperkalemia KW - nephropathy KW - potassium SP - 299 EP - 309 JF - European journal of preventive cardiology JO - Eur J Prev Cardiol VL - 21 IS - 3 N2 - AIMS: In the Ongoing Telmisartan Alone and in Combination with Ramipril Trial (ONTARGET), dual agent renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not reduce the risk of renal and cardiovascular outcomes compared with the single use of either agent. Dual therapy however increased the incidence of hyperkalemia. We examined risk factors for hyper- and hyokalemia and hypothesized that both would be associated with worse cardiovascular and renal outcomes. METHODS: A post-hoc analysis of the ONTARGET trial comparing dual therapy (ramipril and telmisartan) vs monotherapy (ramipril or telmisartan) was performed. The association between serum potassium at week 6 on cardiovascular and renal outcomes during the 56 months follow-up was assessed by multivariate Cox analysis. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The renal outcome was defined as the composite of a doubling of serum creatinine or chronic dialysis. RESULTS: Six weeks after randomization, hyperkalemia developed in 210 (2.7%) patients on dual therapy vs. 264 (1.6%) patients on monotherapy (p < 0.001 vs. dual therapy). Hypokalemia developed in 87 (1.1%) patients on dual therapy vs. 200 (1.2%)patients on monotherapy. Serum potassium was nonlinearly associated with cardiovascular and renal events with a nadir between 4.0-5.0 mmol/l for cardiovascular and 4.0-4.5 mmol/l for renal events such that subjects above or below these values exhibited higher risks. This association was independent of age, gender, diabetes, estimated glomerular filtration rate, systolic blood pressure and diuretic use. CONCLUSIONS: With the precautions stipulated by the protocol of the ONTARGET trial, hypokalemia and hyperkalemia were infrequent events. Nevertheless, both high and low serum potassium were associated with an increased risk of cardiovascular and renal disease. SN - 2047-4881 UR - https://www.unboundmedicine.com/medline/citation/24191305/The_effect_of_ramipril_and_telmisartan_on_serum_potassium_and_its_association_with_cardiovascular_and_renal_events:_results_from_the_ONTARGET_trial_ L2 - http://journals.sagepub.com/doi/full/10.1177/2047487313510678?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -