Nitrates for Chronic Heart Failure: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 JIANGJun-shi ¹ , CUIHuan-di ² , XIAQing-de ³ , DANGLin-lin ¹ ,  YAOYa-li ⁴

1. The First Clinical Medicine College of Lanzhou University, Lanzhou 730000, China;
2. Department Ultrasound, Gansu Provincial Hospital, Lanzhou 730000, China;
3. Department of Cardiology, The People' s Hospital of Lintao County, Lintao 730500, China;
4. Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

YAOYa-li, Email: yaoyalifs@163.com

Keywords：

Chronic heart failure; Nitrates; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160164

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Objectives To systematically assess the efficacy and safety of nitrates for patients with chronic heart failure. Method We searched PubMed, EMbase, Web of Science, The Cochrane Library (Issue 1, 2016), CBM, CNKI, VIP, and WanFang Data to collect randomized controlled trials (RCTs) and cross-over studies about nitrates in the treatment of heart failure from inception to January 4th 2016. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.3 software. Results Ten trials were included involving 414 patients (195 patients in the nitrates group and 219 patients in the control group). The results of meta-analysis showed that, compared with the control group, the nitrates group could reduce arterial blood pressure (MD=-1.91, 95%CI -3.66 to -0.16, P=0.03), pulmonary wedge pressure vessels (PCWP) (MD=-2.00, 95%CI -3.84 to -0.15, P=0.03), increase cardiac index (CI) (MD=0.25, 95%CI 0.09 to 0.42, P=0.003), treadmill exercise time (MD=70.14, 95%CI 55.22 to 85.05, P < 0.000 01); but easily emerge side effects (OR=5.21, 95%CI 2.60 to 10.41, P < 0.000 01). Conclusion Current evidence indicates that nitrates treatment could improve the hemodynamic effect, enhance cardiac output and increase exercise tolerance in patients with heart failure.

Citation： JIANGJun-shi, CUIHuan-di, XIAQing-de, DANGLin-lin, YAOYa-li. Nitrates for Chronic Heart Failure: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(9): 1072-1079. doi: 10.7507/1672-2531.20160164 Copy

1.	中华医学会心血管病学分会.中国心力衰竭诊断和治疗指南2014.中华心血管病杂志, 2014, 42(2): 98-122.
2.	中华医学会心血管病学分会.中国部分地区1980、1990、2000年慢性心力衰竭住院病例回顾性调查.中华心血管病杂志, 2002, 30: 450-454.
3.	Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA, 2004, 292(3): 344-350.
4.	Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med, 2002, 347(18): 1397-1402.
5.	The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med, 1991, 325(5): 293-302.
6.	Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med, 1996, 335(15): 1107-1114.
7.	Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013, 62(16): e147-239.
8.	Higgins J, Altman D, Sterne J, et al. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S In: Sterne J, editor. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Available at: http://www.cochranehandbook.org.
9.	Unverferth DV, Mehegan JP, Magorien RD, et al. Regression of myocardial cellular hypertrophy with vasodilator therapy in chronic congestive heart failure associated with idiopathic dilated cardiomyopathy. Am J Cardiol, 1983, 51(8): 1392-1398.
10.	Franciosa JA, Nordstrom LA, Cohn JN. Nitrate therapy for congestive heart failure. JAMA, 1978, 240(5): 443-446.
11.	Franciosa JA, Goldsmith SR, Cohn JN. Contrasting immediate and long-term effects of isosorbide dinitrate on exercise capacity in congestive heart failure. Am J Med, 1980, 69(4): 559-566.
12.	Leier CV, Huss P, Magorien RD, et al. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation, 1983, 67(4): 817-822.
13.	Wilkes NP, Barin E, Hoschl R, et al. Comparison of the immediate and long-term effects of captopril and isosorbide dinitrate as adjunctive treatment in mild heart failure. Br J Clin Pharmacol, 1989, 28(4): 427-434.
14.	Elkayam U, Amin J, Mehra A, et al. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation, 1990, 82(6): 1954-1961.
15.	Lewis BS, Rabinowitz B, Schlesinger Z, et al. Effect of isosorbide-5-mononitrate on exercise performance and clinical status in patients with congestive heart failure. Results of the Nitrates in Congestive Heart Failure (NICE) Study. Cardiology, 1999, 91(1): 1-7.
16.	Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation, 1999, 99(20): 2652-2657.
17.	Wieshammer S, Hetzel M, Hetzel J, et al. Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study. Cardiology, 2001, 95(2): 61-65.
18.	Tingberg E, Roijer A, Thilen U, et al. Randomized, double-blind, placebo-controlled long-term study of isosorbide-5-mononitrate therapy in patients with left ventricular dysfunction after acute myocardial infarction. Am Heart J, 2003, 145(1): G1-G9.
19.	Bennett BM, Schroder H, Hayward LD, et al. Effect of in vitro organic nitrate tolerance on relaxation, cyclic GMP accumulation, and guanlylate cyclase activation by glyceryl trinitrate and the enantiomers of isoidide dinitrate. Circ Res, 1988, 63(4): 693-701.
20.	Ignarro LJ, Lipton H, Edwards JC, et al. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-Nitrosothiols as active intermediates. J Pharmacol Exp Ther, 1981, 218(3): 739-749.
21.	戚文航.硝酸酯治疗新进展.中华心血管杂志, 2002, 30(3): 187-188.
22.	Elkayam U, Kulick D, McIntosh N, et al. Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. Circulation, 1987, 76(3): 577-584.
23.	Roth A, Kulick D, Freidenberger L, et al. Early tolerance to hemodynamic effects of high dose transdermal nitroglycerin in responders with severe chronic heart failure. J Am Coll Cardiol, 987, 9(4): 858-864.
24.	Packer M, Medina N, Yushak M, et al. Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: Results of a randomized crossover study. Am Heart J, 1985, 109(6): 1293-1299.
25.	Cohn JN, Archibald D, Ziesche S, et al. Effect of vasodilator therapy onpeak oxygen consumption in heart failure: V-HeFT. (Abstr) Circulation, 1987, 76(suppl Ⅳ): Ⅳ-443.
26.	Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med, 1991, 325(5): 303-310.
27.	Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: Results of a Veterans Administration Cooperative Study. N Engl J Med, 1986, 314(24): 1547-1552.
28.	Packer M, Lee WH, Kessler PD, et al. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med, 1987, 317(13): 799-804.
29.	Elkayam U, Roth A, Mehra A, et al. Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure. Circulation, 1991, 84(5): 2040-2048.
30.	Mehra A, Shotan A, Ostrzega E, et al. Escalating nitrate dose overcomes early attenuation of hemodynamic effect caused by nitrate tolerance in patients with heart failure. Am Heart J, 1995, 130(4): 798-805.

1. 中华医学会心血管病学分会.中国心力衰竭诊断和治疗指南2014.中华心血管病杂志, 2014, 42(2): 98-122.
2. 中华医学会心血管病学分会.中国部分地区1980、1990、2000年慢性心力衰竭住院病例回顾性调查.中华心血管病杂志, 2002, 30: 450-454.
3. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA, 2004, 292(3): 344-350.
4. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med, 2002, 347(18): 1397-1402.
5. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med, 1991, 325(5): 293-302.
6. Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med, 1996, 335(15): 1107-1114.
7. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013, 62(16): e147-239.
8. Higgins J, Altman D, Sterne J, et al. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S In: Sterne J, editor. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). Available at: http://www.cochranehandbook.org.
9. Unverferth DV, Mehegan JP, Magorien RD, et al. Regression of myocardial cellular hypertrophy with vasodilator therapy in chronic congestive heart failure associated with idiopathic dilated cardiomyopathy. Am J Cardiol, 1983, 51(8): 1392-1398.
10. Franciosa JA, Nordstrom LA, Cohn JN. Nitrate therapy for congestive heart failure. JAMA, 1978, 240(5): 443-446.
11. Franciosa JA, Goldsmith SR, Cohn JN. Contrasting immediate and long-term effects of isosorbide dinitrate on exercise capacity in congestive heart failure. Am J Med, 1980, 69(4): 559-566.
12. Leier CV, Huss P, Magorien RD, et al. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation, 1983, 67(4): 817-822.
13. Wilkes NP, Barin E, Hoschl R, et al. Comparison of the immediate and long-term effects of captopril and isosorbide dinitrate as adjunctive treatment in mild heart failure. Br J Clin Pharmacol, 1989, 28(4): 427-434.
14. Elkayam U, Amin J, Mehra A, et al. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation, 1990, 82(6): 1954-1961.
15. Lewis BS, Rabinowitz B, Schlesinger Z, et al. Effect of isosorbide-5-mononitrate on exercise performance and clinical status in patients with congestive heart failure. Results of the Nitrates in Congestive Heart Failure (NICE) Study. Cardiology, 1999, 91(1): 1-7.
16. Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation, 1999, 99(20): 2652-2657.
17. Wieshammer S, Hetzel M, Hetzel J, et al. Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study. Cardiology, 2001, 95(2): 61-65.
18. Tingberg E, Roijer A, Thilen U, et al. Randomized, double-blind, placebo-controlled long-term study of isosorbide-5-mononitrate therapy in patients with left ventricular dysfunction after acute myocardial infarction. Am Heart J, 2003, 145(1): G1-G9.
19. Bennett BM, Schroder H, Hayward LD, et al. Effect of in vitro organic nitrate tolerance on relaxation, cyclic GMP accumulation, and guanlylate cyclase activation by glyceryl trinitrate and the enantiomers of isoidide dinitrate. Circ Res, 1988, 63(4): 693-701.
20. Ignarro LJ, Lipton H, Edwards JC, et al. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-Nitrosothiols as active intermediates. J Pharmacol Exp Ther, 1981, 218(3): 739-749.
21. 戚文航.硝酸酯治疗新进展.中华心血管杂志, 2002, 30(3): 187-188.
22. Elkayam U, Kulick D, McIntosh N, et al. Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. Circulation, 1987, 76(3): 577-584.
23. Roth A, Kulick D, Freidenberger L, et al. Early tolerance to hemodynamic effects of high dose transdermal nitroglycerin in responders with severe chronic heart failure. J Am Coll Cardiol, 987, 9(4): 858-864.
24. Packer M, Medina N, Yushak M, et al. Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: Results of a randomized crossover study. Am Heart J, 1985, 109(6): 1293-1299.
25. Cohn JN, Archibald D, Ziesche S, et al. Effect of vasodilator therapy onpeak oxygen consumption in heart failure: V-HeFT. (Abstr) Circulation, 1987, 76(suppl Ⅳ): Ⅳ-443.
26. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med, 1991, 325(5): 303-310.
27. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: Results of a Veterans Administration Cooperative Study. N Engl J Med, 1986, 314(24): 1547-1552.
28. Packer M, Lee WH, Kessler PD, et al. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med, 1987, 317(13): 799-804.
29. Elkayam U, Roth A, Mehra A, et al. Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure. Circulation, 1991, 84(5): 2040-2048.
30. Mehra A, Shotan A, Ostrzega E, et al. Escalating nitrate dose overcomes early attenuation of hemodynamic effect caused by nitrate tolerance in patients with heart failure. Am Heart J, 1995, 130(4): 798-805.

Chinese Journal of Evidence-Based Medicine

Nitrates for Chronic Heart Failure: A Meta-analysis

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