The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and Meta-analysis

Sunil Badve, Suetonia Palmer, Giovanni Strippoli, Matthew Roberts, A Teixeira-Pinto, Neil Boudville, Alan Cass, Carmel Hawley, Swapnil Hiremath, Elaine Pascoe, Vlado Perkovic, GA Whalley, Jonathan Craig, David Johnson

    Research output: Contribution to journalArticle

    Abstract

    Background: Left ventricular mass (LVM) is a widely used surrogate end point in randomized trials involving people with chronic kidney disease (CKD) because treatment-induced LVM reductions are assumed to lower cardiovascular risk. The aim of this study was to assess the validity of LVM as a surrogate end point for all-cause and cardiovascular mortality in CKD.

    Study Design: Systematic review and meta-analysis.

    Setting & Population: Participants with any stages of CKD.

    Selection Criteria for Studies: Randomized controlled trials with 3 or more months’ follow-up that reported LVM data.

    Intervention: Any pharmacologic or nonpharmacologic intervention.

    Outcomes: The surrogate outcome of interest was LVM change from baseline to last measurement, and clinical outcomes of interest were all-cause and cardiovascular mortality. Standardized mean differences (SMDs) of LVM change and relative risk for mortality were estimated using pairwise random-effects meta-analysis. Correlations between surrogate and clinical outcomes were summarized across all interventions combined using bivariate random-effects Bayesian models, and 95% credible intervals were computed.

    Results: 73 trials (6,732 participants) covering 25 intervention classes were included in the meta-analysis. Overall, risk of bias was uncertain or high. Only 3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials; SMD, −0.13; 95% CI, −0.23 to −0.03), renin-angiotensin-aldosterone system inhibitors (13 trials; SMD, −0.28; 95% CI, −0.45 to −0.12), and isosorbide mononitrate (2 trials; SMD, −0.43; 95% CI, −0.72 to −0.14). All interventions had uncertain effects on all-cause and cardiovascular mortality. There were weak and imprecise associations between the effects of interventions on LVM change and all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95% credible interval, −0.13 to 0.59) and cardiovascular mortality (13 trials; 2,327 participants; correlation coefficient, 0.30; 95% credible interval, −0.54 to 0.76).

    Limitations: Limited long-term data, suboptimal quality of included studies.

    Conclusions: There was no clear and consistent association between intervention-induced LVM change and mortality. Evidence for LVM as a valid surrogate end point in CKD is currently lacking.
    Original languageEnglish
    Pages (from-to)554-563
    Number of pages10
    JournalAmerican Journal of Kidney Diseases
    Volume68
    Issue number4
    DOIs
    Publication statusPublished - Oct 2016

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    Badve, S., Palmer, S., Strippoli, G., Roberts, M., Teixeira-Pinto, A., Boudville, N., Cass, A., Hawley, C., Hiremath, S., Pascoe, E., Perkovic, V., Whalley, GA., Craig, J., & Johnson, D. (2016). The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and Meta-analysis. American Journal of Kidney Diseases, 68(4), 554-563. https://doi.org/10.1053/j.ajkd.2016.03.418