盐皮质激素受体拮抗剂在治疗射血分数降低的慢性心力衰竭患者中的应用、副作用及应对方案
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摘要
对于所有有症状的射血分数降低的慢性心力衰竭(HFREF)患者,在血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂的基础上联合使用盐皮质激素受体拮抗剂(MRAs),对改善预后有重要意义。但MRAs因其严重的副反应限制了其在临床上更为广泛的使用,而致命性的高钾血症是最常见的副作用之一。本文主要针对MRAs在治疗HFREF中的应用、主要副作用及应对方案展开综述。
引文
[1]Schiffrin EL. Effects of aldosterone on the vasculature[J].Hypertension,2006,47(3):312-318.
[2]Odermatt A,Kratschmar DV. Tissue-specific modulation of mineralocorticoid receptor function by 11β-hydroxysteroid dehydrogenases:an overview[J]. Mol Cell Endocrinol,2012,350(2):168-186.
[3]Perrier R,Richard S,Sainte-Marie Y,et al. A direct relationship between plasma aldosterone and cardiac L-type Ca2+current in mice[J]. J Physiol,2005,569(Pt 1):153-162.
[4]Young MJ,Rickard AJ. Mechanisms of mineralocorticoid saltinduced hypertension and cardiac fibrosis[J]. Mol Cell Endocrinol,2012,350(2):248-255.
[5]Brilla CG,Weber KT. Reactive and reparative myocardial fibrosis in arterial hypertension in the rat[J]. Cardiovasc Res,1992,26(7):671-677.
[6]Mac Fadyen RJ,Barr CS,Struthers AD. Aldosterone blockade reduces vascular collagen turnover,improves heart rate variability and reduces early morning rise in heart rate in heart failure patients[J]. Cardiovasc Res,1997,35(1):30-34.
[7]Rocha R,Williams GH. Rationale for the use of aldosterone antagonists in congestive heart failure[J]. Drugs,2002,62(5):723-731.
[8]Beygui F,Collet JP,Benoliel J,et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction[J]. Circulation,2006,114(24):2 604-2 610.
[9]Gueder G,Bauersachs J,Frantz S,et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure[J]. Circulation,2007,115(13):1 754-1 761.
[10]Yancy CW,Jessup M,Bozkurt B,et al.2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America[J].J Am Coll Cardiol,2017,70(6):776-803.
[11]Ponikowski P,Voors AA,Anker SD,et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure:the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology(ESC). developed with the special contribution[J].Eur J Heart Fail,2016,18(8):891-975.
[12]Pitt B,Zannad F,Remme WJ,et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators[J]. N Engl J Med,1999,341(10):709-717.
[13]Pitt B,Remme W,Zannad F,et al. Eplerenone,a selective aldosterone blocker,in patients with left ventricular dysfunction after myocardial infarction[J]. N Engl J Med,2003,348(14):1 309-1 321.
[14]Pfeffer MA,Claggett B,Assmann SF,et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist(TOPCAT)trial[J]. Circulation,2015,131(1):34-42.
[15]Heggermont WA,Goethals M,Dierckx R,et al. Should MRAs be at the front row in heart failure? A plea for the early use of mineralocorticoid receptor antagonists in medical therapy for heart failure based on clinical experience[J]. Heart Fail Rev,2016,21(6):699-701.
[16]Savarese G,Carrero JJ,Pitt B,et al. Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction:an analysis of 11 215patients from the Swedish Heart Failure Registry[J]. Eur J Heart Fail,2018,20(9):1 326-1 334.
[17]Struthers AD. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure[J]. J Card Fail,1996,2(1):47-54.
[18]Zannad F,Mcmurray JJ,Krum H,et al. Eplerenone in patients with systolic heart failure and mild symptoms[J]. N Engl J Med,2011,364(1):11-21.
[19]Olivier A,Pitt B,Girerd N,et al. Effect of eplerenone in patients with heart failure and reduced ejection fraction:potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial[J]. Eur J Heart Fail,2017,19(9):1 186-1 197.
[20]Pitt B,Pfeffer MA,Assmann SF,et al. Spironolactone for heart failure with preserved ejection fraction[J]. N Engl J Med,2014,370(15):1 383-1 392.
[21]Juurlink DN,Mamdani M,Kopp A,et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity[J].JAMA,2003,289(13):1 652-1 658.
[22]Abbas S,Ihle P,Harder S,et al. Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data:a population-and insurance-based cohort[J]. Pharmacoepidemiol Drug Saf,2015,24(4):406-413.
[23]Hoss S,Elizur Y,Luria D,et al. Serum potassium levels and outcome in patients with chronic heart failure[J]. Am J Cardiol,2016,118(12):1 868-1 874.
[24]Rossignol P,Dobre D,McMurray JJ,et al. Incidence,determinants,and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy:results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure(EMPHASIS-HF)[J]. Circ Heart Fail,2014,7(1):51-58.
[25]Lainscak M,Pelliccia F,Rosano G,et al. Safety profile of mineralocorticoid receptor antagonists:Spironolactone and eplerenone[J]. Int J Cardiol,2015,200:25-29.
[26]Kolkhof P,Delbeck M,Kretschmer A,et al. Finerenone,a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury[J]. J Cardiovasc Pharmacol,2014,64(1):69-78.
[27]Naegele M,Hernandez AF,Ruschitzka F. Finerenone in heart failure:walking a fine line[J]. Eur Heart J,2016,37(27,SI):2 115-2 117.
[28]Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system[J]. N Engl J Med,2004,351(6):585-592.
[29]Pantanowitz L. Drug-induced hyperkalemia[J]. Am J Med,2002,112(4):334-335.
[30]Cheng TO. Herbal interactions with cardiac drugs[J]. Arch Intern Med,2000,160(6):870-871.
[31]Lepage L,Desforges K,Lafrance JP. New drugs to prevent and treat hyperkalemia[J]. Curr Opin Nephrol Hypertens,2016,25(6):524-528.
[32]Li LY,Harrison SD,Cope MJ,et al. Mechanism of action and pharmacology of patiromer,a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia[J]. J Cardiovasc Pharmacol Ther,2016,21(5):456-465.
[33]Sarwar CMS,Bhagat AA,Anker SD,et al. Role of hyperkalemia in heart failure and the therapeutic use of potassium binders[J]. Handb Exp Pharmacol,2017,243:537-560.
[34]Linder KE,Krawczynski MA,Laskey D. Sodium Zirconium cyclosilicate(ZS-9):a novel agent for the treatment of hyperkalemia[J]. Pharmacotherapy,2016,36(8):923-933.
[35]Davies JI,Band M,Morris A,et al. Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes[J]. Diabetologia,2004,47(10):1 687-1 694.
[36]Hu X,Li S,McMahon EG,et al. Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone[J].Mini Rev Med Chem,2005,5(8):709-718.
[37]B?rfacker L,Kuhl A,Hillisch A,et al. Discovery of BAY94-8862:a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases[J].Chem MedChem,2012,7(8):1 385-1 403.
[38]Fagart J,Hillisch A,Huyet J,et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule[J]. J Biol Chem,2010,285(39):29 932-29 940.
[2]Odermatt A,Kratschmar DV. Tissue-specific modulation of mineralocorticoid receptor function by 11β-hydroxysteroid dehydrogenases:an overview[J]. Mol Cell Endocrinol,2012,350(2):168-186.
[3]Perrier R,Richard S,Sainte-Marie Y,et al. A direct relationship between plasma aldosterone and cardiac L-type Ca2+current in mice[J]. J Physiol,2005,569(Pt 1):153-162.
[4]Young MJ,Rickard AJ. Mechanisms of mineralocorticoid saltinduced hypertension and cardiac fibrosis[J]. Mol Cell Endocrinol,2012,350(2):248-255.
[5]Brilla CG,Weber KT. Reactive and reparative myocardial fibrosis in arterial hypertension in the rat[J]. Cardiovasc Res,1992,26(7):671-677.
[6]Mac Fadyen RJ,Barr CS,Struthers AD. Aldosterone blockade reduces vascular collagen turnover,improves heart rate variability and reduces early morning rise in heart rate in heart failure patients[J]. Cardiovasc Res,1997,35(1):30-34.
[7]Rocha R,Williams GH. Rationale for the use of aldosterone antagonists in congestive heart failure[J]. Drugs,2002,62(5):723-731.
[8]Beygui F,Collet JP,Benoliel J,et al. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction[J]. Circulation,2006,114(24):2 604-2 610.
[9]Gueder G,Bauersachs J,Frantz S,et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure[J]. Circulation,2007,115(13):1 754-1 761.
[10]Yancy CW,Jessup M,Bozkurt B,et al.2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America[J].J Am Coll Cardiol,2017,70(6):776-803.
[11]Ponikowski P,Voors AA,Anker SD,et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure:the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology(ESC). developed with the special contribution[J].Eur J Heart Fail,2016,18(8):891-975.
[12]Pitt B,Zannad F,Remme WJ,et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators[J]. N Engl J Med,1999,341(10):709-717.
[13]Pitt B,Remme W,Zannad F,et al. Eplerenone,a selective aldosterone blocker,in patients with left ventricular dysfunction after myocardial infarction[J]. N Engl J Med,2003,348(14):1 309-1 321.
[14]Pfeffer MA,Claggett B,Assmann SF,et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist(TOPCAT)trial[J]. Circulation,2015,131(1):34-42.
[15]Heggermont WA,Goethals M,Dierckx R,et al. Should MRAs be at the front row in heart failure? A plea for the early use of mineralocorticoid receptor antagonists in medical therapy for heart failure based on clinical experience[J]. Heart Fail Rev,2016,21(6):699-701.
[16]Savarese G,Carrero JJ,Pitt B,et al. Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction:an analysis of 11 215patients from the Swedish Heart Failure Registry[J]. Eur J Heart Fail,2018,20(9):1 326-1 334.
[17]Struthers AD. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure[J]. J Card Fail,1996,2(1):47-54.
[18]Zannad F,Mcmurray JJ,Krum H,et al. Eplerenone in patients with systolic heart failure and mild symptoms[J]. N Engl J Med,2011,364(1):11-21.
[19]Olivier A,Pitt B,Girerd N,et al. Effect of eplerenone in patients with heart failure and reduced ejection fraction:potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial[J]. Eur J Heart Fail,2017,19(9):1 186-1 197.
[20]Pitt B,Pfeffer MA,Assmann SF,et al. Spironolactone for heart failure with preserved ejection fraction[J]. N Engl J Med,2014,370(15):1 383-1 392.
[21]Juurlink DN,Mamdani M,Kopp A,et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity[J].JAMA,2003,289(13):1 652-1 658.
[22]Abbas S,Ihle P,Harder S,et al. Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data:a population-and insurance-based cohort[J]. Pharmacoepidemiol Drug Saf,2015,24(4):406-413.
[23]Hoss S,Elizur Y,Luria D,et al. Serum potassium levels and outcome in patients with chronic heart failure[J]. Am J Cardiol,2016,118(12):1 868-1 874.
[24]Rossignol P,Dobre D,McMurray JJ,et al. Incidence,determinants,and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy:results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure(EMPHASIS-HF)[J]. Circ Heart Fail,2014,7(1):51-58.
[25]Lainscak M,Pelliccia F,Rosano G,et al. Safety profile of mineralocorticoid receptor antagonists:Spironolactone and eplerenone[J]. Int J Cardiol,2015,200:25-29.
[26]Kolkhof P,Delbeck M,Kretschmer A,et al. Finerenone,a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury[J]. J Cardiovasc Pharmacol,2014,64(1):69-78.
[27]Naegele M,Hernandez AF,Ruschitzka F. Finerenone in heart failure:walking a fine line[J]. Eur Heart J,2016,37(27,SI):2 115-2 117.
[28]Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system[J]. N Engl J Med,2004,351(6):585-592.
[29]Pantanowitz L. Drug-induced hyperkalemia[J]. Am J Med,2002,112(4):334-335.
[30]Cheng TO. Herbal interactions with cardiac drugs[J]. Arch Intern Med,2000,160(6):870-871.
[31]Lepage L,Desforges K,Lafrance JP. New drugs to prevent and treat hyperkalemia[J]. Curr Opin Nephrol Hypertens,2016,25(6):524-528.
[32]Li LY,Harrison SD,Cope MJ,et al. Mechanism of action and pharmacology of patiromer,a nonabsorbed cross-linked polymer that lowers serum potassium concentration in patients with hyperkalemia[J]. J Cardiovasc Pharmacol Ther,2016,21(5):456-465.
[33]Sarwar CMS,Bhagat AA,Anker SD,et al. Role of hyperkalemia in heart failure and the therapeutic use of potassium binders[J]. Handb Exp Pharmacol,2017,243:537-560.
[34]Linder KE,Krawczynski MA,Laskey D. Sodium Zirconium cyclosilicate(ZS-9):a novel agent for the treatment of hyperkalemia[J]. Pharmacotherapy,2016,36(8):923-933.
[35]Davies JI,Band M,Morris A,et al. Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes[J]. Diabetologia,2004,47(10):1 687-1 694.
[36]Hu X,Li S,McMahon EG,et al. Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone[J].Mini Rev Med Chem,2005,5(8):709-718.
[37]B?rfacker L,Kuhl A,Hillisch A,et al. Discovery of BAY94-8862:a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases[J].Chem MedChem,2012,7(8):1 385-1 403.
[38]Fagart J,Hillisch A,Huyet J,et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule[J]. J Biol Chem,2010,285(39):29 932-29 940.