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

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• 作者：Sunil V. Badve ; MD¹ ; ² ; ³ ; ⁴ ; ^{sbadve@georgeinstitute.org.au" class="auth_mail" title="E-mail the corresponding author} ; Suetonia C. Palmer ; PhD¹ ; ⁵ ; Giovanni F.M. Strippoli ; PhD⁶ ; ⁷ ; ⁸ ; Matthew A. Roberts ; PhD¹ ; ⁹ ; Armando Teixeira-Pinto ; PhD⁶ ; Neil Boudville ; M Med Sci¹ ; ¹⁰ ; Alan Cass ; PhD¹ ; ¹¹ ; Carmel M. Hawley ; M Med Sci¹ ; ² ; ¹² ; Swapnil S. Hiremath ; MD ; MPH¹³ ; ¹⁴ ; Elaine M. Pascoe ; M Biostat¹ ; ² ; Vlado Perkovic ; PhD¹ ; ⁴ ; Gillian A. Whalley ; PhD¹⁵ ; Jonathan C. Craig ; PhD¹ ; ⁶ ; ¹⁶ ; David W. Johnson ; MD ; PhD¹ ; ² ; ¹²
• 关键词：Left ventricular mass (LVM) ; LVM regression ; cardiovascular mortality ; chronic kidney disease (CKD) ; left ventricular hypertrophy ; surrogate endpoint ; surrogate outcome ; cardioprotection ; erythropoiesis-stimulating agent (ESA) ; renin-angiotensin-aldosterone system (RAAS) inhibitor ; nitrate ; meta-analysis
• 刊名：American Journal of Kidney Diseases
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：68
• 期：4
• 页码：554-563
• 全文大小：1508 K

文摘

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.