Effects of mineralocorticoid receptor antagonists on left ventricular mass in chronic kidney disease patients:a systematic review and meta-analysis
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- 英文论文题名：Effects of mineralocorticoid receptor antagonists on left ventricular mass in chronic kidney disease patients:a systematic review and meta-analysis
- 论文作者：RenJie Lu ; Yan Zhang ; Xishan Zhu ; Zhengda Fan ; Shanmei Zhu ; Fenglei Tang
- 英文论文作者：RenJie Lu ; Yan Zhang ; Xishan Zhu ; Zhengda Fan ; Shanmei Zhu ; Fenglei Tang ; Department of Pharmacy The Third People's Hospital of Changzhou ; Department of Internal Medicine The Third People's Hospital of Changzhou ; Department of Urinary Surgery The Third People's Hospital of Changzhou
- 年：2016
- 作者机构：Department of Pharmacy The Third People's Hospital of Changzhou;Department of Internal Medicine The Third People's Hospital of Changzhou;Department of Urinary Surgery The Third People's Hospital of Changzhou;
- 英文论文关键词：Aldosterone receptor antagonist ; Chronic kidney disease ; Left ventricular mass ; Cardiovascular events ; Mortality
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R692
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：12
- 文件大小：2246k
- 原文格式：O
- 会议级别：全国
摘要
Background Mineralocorticoid receptor antagonists(MRAs) are used widely in treatment of heart failure,but their effects on cardiovascular complications and mortality of chronic kidney disease(CKD) are not well known.Thus,we aim to assess such therapeutic effects of MRAs on CKD.Methods Electronic literature published in any language until Dec 31,2015,was systematically searched on PubMed,Embase,and Cochrane Central Register of Controlled Trials.Primary outcome was left ventricular mass(LVM) or LVM index(LVMI),and secondary outcome was all-cause mortality and major adverse cardiovascular events(MACEs).Results of continuous outcomes were pooled using mean difference(MD)and standard mean difference(SMD).Risk ratios(RRs) with 95%confidence intervals(CIs) were pooled using a random- or fixed-effects model.Results Totally 12 studies(6 randomized controlled trials with 1003 participants) involving 4935 patients were included.MRA treatment versus non-MRA treatment resulted in a significant change of 0.93 SMD(standard mean difference) in LVM(LVMI),a significant reduction of 22%in all-cause mortality,a significant reduction of incidence of MACEs(RR 0.65,P = 0.001),significantly higher prevalence rates of hyperkalemia(>5.5 mmol/L),but no significant change in prevalence rates of severe hyperkalemia(>6.0 mmol/L).Conclusion MRA benefits CKD patients in terms of LVMI,all-cause mortality,and MACEs with no incidence of severe hyperkalemia.Nevertheless,the real effects of MRAs on cardiovascular events and mortality as well as their safety in CKD patients should be identified by further studies with prospective and large-sample clinical trials.
Background Mineralocorticoid receptor antagonists(MRAs) are used widely in treatment of heart failure,but their effects on cardiovascular complications and mortality of chronic kidney disease(CKD) are not well known.Thus,we aim to assess such therapeutic effects of MRAs on CKD.Methods Electronic literature published in any language until Dec 31,2015,was systematically searched on PubMed,Embase,and Cochrane Central Register of Controlled Trials.Primary outcome was left ventricular mass(LVM) or LVM index(LVMI),and secondary outcome was all-cause mortality and major adverse cardiovascular events(MACEs).Results of continuous outcomes were pooled using mean difference(MD)and standard mean difference(SMD).Risk ratios(RRs) with 95%confidence intervals(CIs) were pooled using a random- or fixed-effects model.Results Totally 12 studies(6 randomized controlled trials with 1003 participants) involving 4935 patients were included.MRA treatment versus non-MRA treatment resulted in a significant change of 0.93 SMD(standard mean difference) in LVM(LVMI),a significant reduction of 22%in all-cause mortality,a significant reduction of incidence of MACEs(RR 0.65,P = 0.001),significantly higher prevalence rates of hyperkalemia(>5.5 mmol/L),but no significant change in prevalence rates of severe hyperkalemia(>6.0 mmol/L).Conclusion MRA benefits CKD patients in terms of LVMI,all-cause mortality,and MACEs with no incidence of severe hyperkalemia.Nevertheless,the real effects of MRAs on cardiovascular events and mortality as well as their safety in CKD patients should be identified by further studies with prospective and large-sample clinical trials.
Background Mineralocorticoid receptor antagonists(MRAs) are used widely in treatment of heart failure,but their effects on cardiovascular complications and mortality of chronic kidney disease(CKD) are not well known.Thus,we aim to assess such therapeutic effects of MRAs on CKD.Methods Electronic literature published in any language until Dec 31,2015,was systematically searched on PubMed,Embase,and Cochrane Central Register of Controlled Trials.Primary outcome was left ventricular mass(LVM) or LVM index(LVMI),and secondary outcome was all-cause mortality and major adverse cardiovascular events(MACEs).Results of continuous outcomes were pooled using mean difference(MD)and standard mean difference(SMD).Risk ratios(RRs) with 95%confidence intervals(CIs) were pooled using a random- or fixed-effects model.Results Totally 12 studies(6 randomized controlled trials with 1003 participants) involving 4935 patients were included.MRA treatment versus non-MRA treatment resulted in a significant change of 0.93 SMD(standard mean difference) in LVM(LVMI),a significant reduction of 22%in all-cause mortality,a significant reduction of incidence of MACEs(RR 0.65,P = 0.001),significantly higher prevalence rates of hyperkalemia(>5.5 mmol/L),but no significant change in prevalence rates of severe hyperkalemia(>6.0 mmol/L).Conclusion MRA benefits CKD patients in terms of LVMI,all-cause mortality,and MACEs with no incidence of severe hyperkalemia.Nevertheless,the real effects of MRAs on cardiovascular events and mortality as well as their safety in CKD patients should be identified by further studies with prospective and large-sample clinical trials.
引文
[1]Matsushita K,Ballew SH,Coresh J(2015)Influence of chronic kidney disease on cardiac structure and function.Curr Hypertens Rep 17:581
[2]Tomino Y(2014)Pathogenesis and treatment of chronic kidney disease:a review of our recent basic and clinical data.Kidney Blood Press Res 39:450-489
[3]Gansevoort RT,Correa-Rotter R,Hemmelgarn BR et al(2013)Chronic kidney disease and cardiovascular risk:epidemiology,mechanisms,and prevention.Lancet 382:339-352
[4]Foley RN,Curtis BM,Randell EW et al(2010)Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease.Clin J Am Soc Nephrol 5:805-813
[5]Collins AJ,Li S,Gilbertson DT et al(2003)Chronic kidney disease and cardiovascular disease in the Medicare population.Kidney Int Suppl S24-S31
[6]Hill NR,Lasserson D,Thompson B et al(2014)Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease(BARACK D)trial-a multi-centre,prospective,randomised,open,blinded end-point,36-month study of 2616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone:study protocol for a randomized controlled trial.Trials 15:160
[7]Muntner P,He J,Astor BC et al(2005)Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease:results from the atherosclerosis risk in communities study.J Am Soc Nephrol 16:529-538
[8]Brewster UC,Setaro JF,Perazella MA(2003)The renin-angiotensin-aldosterone system:cardiorenal effects and implications for renal and cardiovascular disease states.Am J Med Sci 326:15-24
[9]Pitt B,Zannad F,Remme WJ et al(1999)The effect of spironolactone on morbidity and mortality in patients with severe heart failure.Randomized Aldactone Evaluation Study investigators.N Engl J Med 341:709-717
[10]Zannad F,McMurray JJ,Krum H et al(2011)Eplerenone in patients with systolic heart failure and mild symptoms.N Engl J Med 364:11-21
[11]Vukusich A,Kunstmann S,Varela C et al(2010)A randomized,double-blind,placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients.Clin J Am Soc Nephrol 5:1380-1387
[12]Pitt B,Kober L,Ponikowski P et al(2013)Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease:a randomized,double-blind trial.Eur Heart J 34:2453-2463
[13]Boesby L,Elung-Jensen T,Strandgaard S et al(2013)Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4-a randomized controlled study.PLoS ONE 8:e64549
[14]Taheri S,Mortazavi M,Pourmoghadas A et al(2012)A prospective double-blind randomized placebo-controlled clinical trial to evaluate the safety and efficacy of spironolactone in patients with advanced congestive heart failure on continuous ambulatory peritoneal dialysis.Saudi J Kidney Dis Transpl 23:507-512
[15]Chung YW,Yang YH,Wu CK et al(2016)Spironolactone is associated with reduced risk of new-onset atrial fibrillation in patients receiving renal replacement therapy.Int J Cardiol 202:962-966
[16]Bomback AS(2016)Mineralocorticoid receptor antagonists in end-stage renal disease:efficacy and safety.Blood Purif41:166-170
[17]Walsh M,Manns B,Garg AX et al(2015)The safety of eplerenone in hemodialysis patients:a noninferiority randomized controlled trial.Clin J Am Soc Nephrol 10:1602-1608
[18]Stroup DF,Berlin JA,Morton SC et al(2000)Meta-analysis of observational studies in epidemiology:a proposal for reporting.Meta-analysis of Observational Studies in Epidemiology(MOOSE)group.JAMA 283:2008-2012
[19]Feniman-De-Stefano GM,Zanati-Basan SG,De Stefano LM et al(2015)Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients.Ther Adv Cardiovasc Dis 9:158-167
[20]Edwards NC,Steeds RP,Stewart PM et al(2009)Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease:a randomized controlled trial.J Am Coll Cardiol 54:505-512
[21]Vardeny O,Wu DH,Desai A et al(2012)Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure:insights from RALES(Randomized Aldactone Evaluation Study).J Am Coll Cardiol60:2082-2089
[22]Flevari P,Kalogeropoulou S,Drakou A et al(2013)Spironolactone improves endothelial and cardiac autonomic function in non heart failure hemodialysis patients.J Hypertens 31:1239-1244
[23]Eschalier R,McMurray JJ,Swedberg K et al(2013)Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function:analyses of the EMPHASIS-HF study subgroups(Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure).J Am Coll Cardiol 62:1585-1593
[24]Ito Y,Mizuno M,Suzuki Y et al(2014)Long-term effects of spironolactone in peritoneal dialysis patients.J Am Soc Nephrol25:1094-1102
[25]Inampudi C,Parvataneni S,Morgan CJ et al(2014)Spironolactone use and higher hospital readmission for Medicare beneficiaries with heart failure,left ventricular ejection fraction<45%,and estimated glomerular filtration rate<45 ml/min/1.73 m(2.).Am J Cardiol 114:79-82
[26]Matsumoto Y,Mori Y,Kageyama S et al(2014)Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients.J Am Coll Cardiol 63:528-536
[27]Hassan M,Qureshi W,Sroujieh LS et al(2014)Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease.J Renin Angiotensin Aldosterone Syst 15:278-285
[28]Oh J,Kang SM,Song MK et al(2015)Clinical benefit of spironolactone in patients with acute decompensated heart failure and severe renal dysfunction:data from the Korean Heart Failure Registry.Am Heart J 169(713-720):e3
[29]Lin C,Zhang Q,Zhang H et al(2016)Long-term effects of low-dose spironolactone on chronic dialysis patients:a randomized Placebo-Controlled Study.J Clin Hypertens(Greenwich)18:121-128
[30]Taheri S,Mortazavi M,Shahidi S et al(2009)Spironolactone in chronic hemodialysis patients improves cardiac function.Saudi J Kidney Dis Transpl 20:392-397
[31]Agarwal R(2010)Blood pressure and mortality among hemodialysis patients.Hypertension 55:762-768
[32]Iraqi W,Rossignol P,Angioi M et al(2009)Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure:insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study(EPHESUS)study.Circulation 119:2471-2479
[33]Voelkl J,Alesutan I,Leibrock CB et al(2013)Spironolactone ameliorates PIT 1-dependent vascular osteoinduction in klotho-hypomorphic mice.J Clin Invest 123:812-822
[34]Brown NJ(2013)Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis.Nat Rev Nephrol 9:459-469
[35]Kannan A,Poongkunran C,Balamuthusamy S(2014)Effect of spironolactone in CV mortality in hemodialysis patients.J Am Coll Cardiol 64:528-529
[2]Tomino Y(2014)Pathogenesis and treatment of chronic kidney disease:a review of our recent basic and clinical data.Kidney Blood Press Res 39:450-489
[3]Gansevoort RT,Correa-Rotter R,Hemmelgarn BR et al(2013)Chronic kidney disease and cardiovascular risk:epidemiology,mechanisms,and prevention.Lancet 382:339-352
[4]Foley RN,Curtis BM,Randell EW et al(2010)Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease.Clin J Am Soc Nephrol 5:805-813
[5]Collins AJ,Li S,Gilbertson DT et al(2003)Chronic kidney disease and cardiovascular disease in the Medicare population.Kidney Int Suppl S24-S31
[6]Hill NR,Lasserson D,Thompson B et al(2014)Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease(BARACK D)trial-a multi-centre,prospective,randomised,open,blinded end-point,36-month study of 2616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone:study protocol for a randomized controlled trial.Trials 15:160
[7]Muntner P,He J,Astor BC et al(2005)Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease:results from the atherosclerosis risk in communities study.J Am Soc Nephrol 16:529-538
[8]Brewster UC,Setaro JF,Perazella MA(2003)The renin-angiotensin-aldosterone system:cardiorenal effects and implications for renal and cardiovascular disease states.Am J Med Sci 326:15-24
[9]Pitt B,Zannad F,Remme WJ et al(1999)The effect of spironolactone on morbidity and mortality in patients with severe heart failure.Randomized Aldactone Evaluation Study investigators.N Engl J Med 341:709-717
[10]Zannad F,McMurray JJ,Krum H et al(2011)Eplerenone in patients with systolic heart failure and mild symptoms.N Engl J Med 364:11-21
[11]Vukusich A,Kunstmann S,Varela C et al(2010)A randomized,double-blind,placebo-controlled trial of spironolactone on carotid intima-media thickness in nondiabetic hemodialysis patients.Clin J Am Soc Nephrol 5:1380-1387
[12]Pitt B,Kober L,Ponikowski P et al(2013)Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease:a randomized,double-blind trial.Eur Heart J 34:2453-2463
[13]Boesby L,Elung-Jensen T,Strandgaard S et al(2013)Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4-a randomized controlled study.PLoS ONE 8:e64549
[14]Taheri S,Mortazavi M,Pourmoghadas A et al(2012)A prospective double-blind randomized placebo-controlled clinical trial to evaluate the safety and efficacy of spironolactone in patients with advanced congestive heart failure on continuous ambulatory peritoneal dialysis.Saudi J Kidney Dis Transpl 23:507-512
[15]Chung YW,Yang YH,Wu CK et al(2016)Spironolactone is associated with reduced risk of new-onset atrial fibrillation in patients receiving renal replacement therapy.Int J Cardiol 202:962-966
[16]Bomback AS(2016)Mineralocorticoid receptor antagonists in end-stage renal disease:efficacy and safety.Blood Purif41:166-170
[17]Walsh M,Manns B,Garg AX et al(2015)The safety of eplerenone in hemodialysis patients:a noninferiority randomized controlled trial.Clin J Am Soc Nephrol 10:1602-1608
[18]Stroup DF,Berlin JA,Morton SC et al(2000)Meta-analysis of observational studies in epidemiology:a proposal for reporting.Meta-analysis of Observational Studies in Epidemiology(MOOSE)group.JAMA 283:2008-2012
[19]Feniman-De-Stefano GM,Zanati-Basan SG,De Stefano LM et al(2015)Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients.Ther Adv Cardiovasc Dis 9:158-167
[20]Edwards NC,Steeds RP,Stewart PM et al(2009)Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease:a randomized controlled trial.J Am Coll Cardiol 54:505-512
[21]Vardeny O,Wu DH,Desai A et al(2012)Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure:insights from RALES(Randomized Aldactone Evaluation Study).J Am Coll Cardiol60:2082-2089
[22]Flevari P,Kalogeropoulou S,Drakou A et al(2013)Spironolactone improves endothelial and cardiac autonomic function in non heart failure hemodialysis patients.J Hypertens 31:1239-1244
[23]Eschalier R,McMurray JJ,Swedberg K et al(2013)Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function:analyses of the EMPHASIS-HF study subgroups(Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure).J Am Coll Cardiol 62:1585-1593
[24]Ito Y,Mizuno M,Suzuki Y et al(2014)Long-term effects of spironolactone in peritoneal dialysis patients.J Am Soc Nephrol25:1094-1102
[25]Inampudi C,Parvataneni S,Morgan CJ et al(2014)Spironolactone use and higher hospital readmission for Medicare beneficiaries with heart failure,left ventricular ejection fraction<45%,and estimated glomerular filtration rate<45 ml/min/1.73 m(2.).Am J Cardiol 114:79-82
[26]Matsumoto Y,Mori Y,Kageyama S et al(2014)Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients.J Am Coll Cardiol 63:528-536
[27]Hassan M,Qureshi W,Sroujieh LS et al(2014)Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease.J Renin Angiotensin Aldosterone Syst 15:278-285
[28]Oh J,Kang SM,Song MK et al(2015)Clinical benefit of spironolactone in patients with acute decompensated heart failure and severe renal dysfunction:data from the Korean Heart Failure Registry.Am Heart J 169(713-720):e3
[29]Lin C,Zhang Q,Zhang H et al(2016)Long-term effects of low-dose spironolactone on chronic dialysis patients:a randomized Placebo-Controlled Study.J Clin Hypertens(Greenwich)18:121-128
[30]Taheri S,Mortazavi M,Shahidi S et al(2009)Spironolactone in chronic hemodialysis patients improves cardiac function.Saudi J Kidney Dis Transpl 20:392-397
[31]Agarwal R(2010)Blood pressure and mortality among hemodialysis patients.Hypertension 55:762-768
[32]Iraqi W,Rossignol P,Angioi M et al(2009)Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure:insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study(EPHESUS)study.Circulation 119:2471-2479
[33]Voelkl J,Alesutan I,Leibrock CB et al(2013)Spironolactone ameliorates PIT 1-dependent vascular osteoinduction in klotho-hypomorphic mice.J Clin Invest 123:812-822
[34]Brown NJ(2013)Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis.Nat Rev Nephrol 9:459-469
[35]Kannan A,Poongkunran C,Balamuthusamy S(2014)Effect of spironolactone in CV mortality in hemodialysis patients.J Am Coll Cardiol 64:528-529