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.
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 language | English |
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Pages (from-to) | 554-563 |
Number of pages | 10 |
Journal | American Journal of Kidney Diseases |
Volume | 68 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 2016 |