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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 2  |  Page : 74-78

Short-term use of statins as an adjuvant therapy in patients with idiopathic dilated cardiomyopathy


1 Department of Pathology, RUHS Medical College, Jaipur, Rajasthan, India
2 Department of Medicine, S. P. Medical College, Bikaner, Rajasthan, India
3 Department of Dentistry, S. P. Medical College, Bikaner, Rajasthan, India

Date of Web Publication8-May-2018

Correspondence Address:
Jitendra Acharya
Department of Dentistry, S.P. Medical College, Bikaner, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AIHB.AIHB_9_18

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  Abstract 

Objective: Echocardiographic assessment of cardiac functions in patients with idiopathic dilated cardiomyopathy before and after using statins as adjuvant therapy. Methodology: With the study duration of 12 weeks 40 patients with idiopathic dilated cardiomyopathy with the New York Heart Association Class II and III were selected and randomly divided into two groups. Group A patients received 10 mg/day of atorvastatin along with usual care and Group B patients received usual care of chronic heart failure. anthropometric, biochemical, echocardiography, 6-min walk test and serum lipid profile were done at baseline and at the end of the study in both the groups. All the data were statistically analysed using 't'-test. Results/Observations: In both the groups, mean ejection fraction (EF) was comparable. It increased in Group A, i.e., study group from 28.92% ±1.63% to 34.18% ±1.27% (P < 0.02). There was significant reduction observed in left ventricular and systolic volume from 194.9 ± 57.34 ml/m2 to 154.15 ± 44.67 ml/m2 (P < 0.002). At the end of the study, 6-min walk test's mean also improved from 310 ± 10.71 to 335 ± 8.71 m (P < 0.001). No major side effects, dropouts and deaths were observed. Conclusion: Statins as an adjuvant therapy improve EF decreases ventricular remodelling and also help in improving the functional class of patients suffering from idiopathic dilated cardiomyopathy.

Keywords: Adjunct therapy, dilated cardiomyopathy, statins


How to cite this article:
Priya N, Agarwal R P, Choudhary V, Budania S, Acharya J. Short-term use of statins as an adjuvant therapy in patients with idiopathic dilated cardiomyopathy. Adv Hum Biol 2018;8:74-8

How to cite this URL:
Priya N, Agarwal R P, Choudhary V, Budania S, Acharya J. Short-term use of statins as an adjuvant therapy in patients with idiopathic dilated cardiomyopathy. Adv Hum Biol [serial online] 2018 [cited 2020 Jul 8];8:74-8. Available from: http://www.aihbonline.com/text.asp?2018/8/2/74/232031


  Introduction Top


Heart failure represents a complex clinical syndrome characterised by abnormalities of ventricular functions and neurohormonal regulations which are accompanied by effort intolerance, fluid retention and reduced longevity. Prognosis of chronic heart failure (CHF) is still grave and comparable to malignant diseases. Idiopathic dilated cardiomyopathy is one of its major causes. The American heart association guidelines for evaluation and management of CHF in adult defined heart failure as, 'complex clinical syndrome that can result from any structural and functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood'.[1] In many cases, heart failure is caused by conditions in which normal heart is suddenly presented with load that exceeds its capacity or in which ventricular filling is impaired.[2] It is seen that prevalence of heart failure increases dramatically with age, occurring in 1%–2% of persons aged 45–54 years and up to 10% of individuals older than 75 years.[3],[4] Various risk factors for heart failure include coronary artery disease, hypertension, diabetes mellitus, obesity, renal insufficiency, family history of cardiomyopathy and valvular heart diseases. CHF becomes the proinflammatory state with neurohormonal imbalances. Sympathoadrenal system, renin-angiotensin-aldosterone system, arginine vasopressin, oxidative stress and inflammatory cytokines interleukin-1 (IL-1), IL-6 and tumour necrosis factor-alpha play an important role in the progression of CHF. C-reactive protein levels in the blood are also increased in patients with idiopathic dilated cardiomyopathy.

'Statin' due to their pleiotropic effects may prove beneficial in this setting. Statin originally designed to lower plasma cholesterol has been hailed as aspirin of new millennium. Statins consistently reduce cardiovascular risk.[5],[6] A reduction in recurrent coronary events has been observed as early as 16 weeks after initiation of treatment.[7],[8] This time frame is too short to ascribe the positive effects of cholesterol reduction alone. The idea of statin-mediated effects beyond cholesterol lowering, so-called pleiotropic effects has thus triggered an avalanche of research in recent years. Statins are of proven clinical benefit in coronary heart disease at least in those who do not have heart failure.[6],[9],[10] One of the important determinants of cardiac function is left ventricular systolic function which is determined by preload, afterload, myocardial contractility and heart rate. Statins have been shown to down-regulate ATI receptor, inhibit proinflammatory cytokines, increase nitric oxide synthesis at the endothelial level and stimulate neoangiogenesis.

After knowing the beneficial effect of statins in patients with the idiopathic dilated cardiomyopathy – this present study was conducted to see the effect of atorvastatin (10 mg/day) on cardiac functions and symptoms in patients with idiopathic dilated cardiomyopathy.


  Methodology Top


This case–controlled study was conducted in the Department of Medicine, at B. D. Sharma Medical College, Rohtak, and Haryana, India with study duration of 12 weeks. Forty patients with idiopathic dilated cardiomyopathy with the New York Heart Association (NYHA) Class II or III and left ventricular ejection fraction (EF) <40% were selected randomly. The exclusion criteria of the study included chronic obstructive pulmonary disease, valvular heart disease, congenital heart disease, pregnancy, thyroid disorder, diabetes mellitus, hypertension, chronic Kidney disease and chronic liver disease. Patients were randomly divided into two groups, treatment Group (Group A) and control Group (Group B). Complete biochemical, anthropometric, clinical and laboratory tests were conducted of enrolled patients. Echocardiographic assessment, 6-min walk test, serum lipid profile were done of all patients at baseline and at the end of the study. All patients were on angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretics. Both groups received usual care and drugs for CHF, but the treatment groups, i.e., Group A received additional atorvastatin10 mg/day.

Statistical analysis

Data were presented as a mean ± standard error. For statistical analysis, Student's 't'-test was applied to compare differences in various indices in both the groups.


  Results Top


The mean age of patients in both treatment and control group was comparable, i.e., 43.3 ± 5.52 and 48.5 ± 5.14 years. Male and female ratio in cases and control were sex matched, i.e., 45:55. Blood sugars, HbA1c, serum creatinine, serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase and serum uric acid at baseline were in normal range in both groups, and no significant difference was observed [Table 1], [Figure 1]. Mean cholesterol level in Group A was 158.75 mg% at baseline, and it declined to 155.85 mg% at the end of the study [Table 2]. However, the fall was insignificant (P< 0.9). Whereas in placebo Group B, mean serum cholesterol was 166.7 mg% at baseline and 171.25 mg% at the end of trial [Table 2], [Figure 2], but again the difference was insignificant.
Table 1: Demographic profile and biochemical parameters of study and control group

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Figure 1: Demographic profile and biochemical parameters of study and control group.

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Table 2: Comparative table of Group A at 0 and 12th weeks

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Figure 2: Comparative table of Group A at 0 and 12 weeks.

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At the start of the study, i.e., at 0 week all the parameters such as serum cholesterol, 6-min walk test, ejection fraction, left ventricular and systolic volume (LVESV), left ventricular end diastolic diameter (LVEDD) and Left ventricular end systolic diameter left ventricular end systolic diameter (LVESD) in both the groups had insignificant value. Whereas at the end of the study, i.e., at 12th week in the treatment group, significant changes were observed in three parameters, i.e., 6-min walk test, EF and LVESV. There was significant improvement in 6-min walk test in the treatment group (Group A), at the start of the study, it was 310 ± 10.71 m, and it increased significantly to 335 ± 8.71 m at the end of the study (P< 0.001) as shown in [Table 3]. However, in Group B, i.e., it increased from 314 ± 8.90 m to 320 ± 10.21 m, but the increase was insignificant (P< 0.1) [Table 3], [Figure 3].
Table 3: Comparative table of Group B at 0 and 12th week

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Figure 3: Comparative table of Group B at 0 and 12 weeks.

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Echocardiographic parameters compared were EF, LVESV, LVEDD and LVESD in both treatment and control groups. EF in Group A and B was 28.92 and 28.4 at the start of the study but after 12 weeks atorvastatin treatment, there was a significant improvement in Group A – i.e., EF increased up to 34.18, whereas in group B we observed value of 27.18 [Table 4]. Similarly, LVESV in Group A was 194.9 ± 57.34 ml/m 2 at the start of the study and 154 ± 44.67 ml/m 2 at the end of the study (P< 0.02), this difference was statistically significant. LVEDD and LVESD were 60.15 ± 8.51 mm and 49.15 ± 9.95 mm at baseline in the treatment group and at the end of the study LVEDD and LVESD were 59.5 ± 9.46 mm and 48.92 ± 9.47 mm, respectively, in Group A [Table 4]. However, this decline in both LVEDD and LVESD was insignificant.
Table 4: Comparison of Group A (case) and Group B (control) at before treatment and after treatment

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  Discussion Top


CHF represents major health burden and the pathophysiology of heart failure is complex. Many studies have been undertaken to study the role of statins in patients with CHF due to idiopathic dilated cardiomyopathy which is an important cause of heart failure. This study has been conducted to see the effects of statin on cardiac functions in patients with idiopathic dilated cardiomyopathy as also previously done by Node et al.[11] The present study has shown that short-term use of statins is not associated with any significant drastic change in mean serum cholesterol level further reinforcing the result of previous studies that the pleiotropic effect of statins is responsible for this benefit of short-term use of statins. Tamara et al. studied 55 patients with heart failure and demonstrated that statin therapy is associated with improved survival in both, i.e., chronic and non-ischaemic heart failure.[12] The anti-inflammatory properties of statins may confer greater benefits than just reducing the risk of arterial fibrillation.

In our study, improvement in EF in the treatment group was from 29% to 34% using 10 mg atorvastatin and was comparable to study conducted by de Lorgeril et al.[13] In their study, 6% absolute increase in EF as compared to baseline after 12 weeks of simvastatin therapy. Similarly, another study conducted by Sola et al., over 108 patients on non-ischaemic dilated cardiomyopathy had shown beneficial effects of statins.[14] It was double-blind placebo controlled study using 20 mg/day atorvastatin in the study group. In this study, EF improved from 33% to 37%.

In our study, the 6-min walk test, used as a predictor of functional capacity had also shown symptomatic improvement in the study group patients when given atorvastatin in addition to standard treatment of heart failure. Among the patients, 10% of patients deteriorated, 15% had no change and 75% of patients showed improvement. This parameter was comparable to study of Node et al. which had also shown NYHA functional class improvement in 40% of the patients and 56% remained same.[11]

The present study had also shown the effect of the use of statin in ventricular remodelling. In the trial LVESV decreased in treatment group from 195 to 154 ml/m 2, this may be the cause of the increase in ejection fraction. It was also seen that LVEDD and LVESD decreased in the treatment group which was on a statin, thus improving the contractility of myocardium, but this decrease in our study had not been significant as shown in earlier studies by other workers. In addition, a study by Hognestad et al. showed that analysis of all surviving patients from the optimal study showed that initiation of β-blocker and statin treatment early after myocardial infarction complicated by heart failure was associated with reduced morbidity and mortality.[15] Keeping all in mind, the results of the present study also supports the view of the beneficial effect of statins in patients with idiopathic dilated cardiomyopathy and this had been explained on the bases of pleiotropic effect of statins.


  Conclusion Top


Heart failure is a major health burden and idiopathic dilated cardiomyopathy has been an important cause for it. Echocardiography with Doppler assessment is a very useful investigation for diagnosis showing global hypokinesia with reduced LV functions. Statins act at the pathophysiological level and hence can halt the progression of disease process, especially in patients with mild-to-moderate heart failure.

For heart failure diuretics, digoxin, β-blockers, ACE inhibitors, aldosterone receptor blocker have been used widely resulting in a functional improvement in patients. However, prognosis has remained fairly poor. Hence, newer approaches are under research. One major advancement is the use of statins in patients with mild-to-moderate heart failure, and the present study has been undertaken for the same. Results have shown the beneficial affect of statin due to their pleiotropic properties resulting in an improvement in EF, decreasing ventricular remodelling and improving the functional class of patients.

Thus, we can conclude that statins are currently the most effective method to pharmacologically decrease total plasma cholesterol levels. Apart from the well-known low-density lipoprotein and cholesterol-lowering effect, statins have been postulated to exert beneficial effects due to so-called 'plieotropic' or 'non-lipid' effects. However, at present, although the clinical implications of these beneficial 'non-lipid' effects seem promising, properly designed, large, multi-centre, prospective, controlled trials are needed to validate the use of statins for indications other than primary and secondary preventions of vascular disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: Executive summary A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1995 guidelines for the evaluation and management of heart failure): Developed in collaboration with the international society for heart and lung transplantation; endorsed by the heart failure society of America. Circulation 2001;104:2996-3007.  Back to cited text no. 1
[PUBMED]    
2.
Braunwal E, Rass J Jr., Sonnenblick EH. Mechanism of Contraction of Normal and Failing Heart. 2nd ed. Beston: Little Brown; 1976. p. 417.  Back to cited text no. 2
    
3.
Dallas TX. American Heart Association: Heart Disease and Stroke Stastistics-2004 Update. American Heart Association; 2003.  Back to cited text no. 3
    
4.
Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: The Framingham study. J Am Coll Cardiol 1993;22:6A-13A.  Back to cited text no. 4
    
5.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7.  Back to cited text no. 5
    
6.
Tonkin A, Aylward P, Colquohoun D, Gusziou P, Harris P, Hunt D, et al. Prevention of cardiovascular events and death with pravastatin in patients with coronary artery disease and broad range of initial cholesterol level. (LIPID study group). N Engl J Med 1998;339:1349-57.  Back to cited text no. 6
    
7.
Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA 2001;285:1711-8.  Back to cited text no. 7
    
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Vaughan CJ, Gotto AM Jr., Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000;35:1-0.  Back to cited text no. 8
    
9.
Pedersen TR, Kjekshus J, Berg K, Haghfelt T, Fairgeman O, Thorgersson G, et al. Scandinavian, Simastatin Survival Study investigator randomized trial of Cholesterol lowering in 4444 patients with coronary heart disease; the Scandinavian Simvastatin Survival Study. Lancet 1994;344:1383-9.  Back to cited text no. 9
    
10.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events trial Investigators. N Engl J Med 1996;335:1001-9.  Back to cited text no. 10
    
11.
Node K, Fujita M, Kitakaze M, Hori M, Liao JK. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 2003;108:839-43.  Back to cited text no. 11
    
12.
Horwich TB, MacLellan WR, Fonarow GC. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol 2004;43:642-8.  Back to cited text no. 12
    
13.
de Lorgeril M, Salen P, Bontemps L, Belichard P, Geyssant A, Itti R, et al. Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients. J Cardiovasc Pharmacol 1999;33:473-8.  Back to cited text no. 13
    
14.
Sola S, Mir MQ, Lerakis S, Tandon N, Khan BV. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 2006;47:332-7.  Back to cited text no. 14
    
15.
Hognestad A, Dickstein K, Myhre E, Snapinn S, Kjekshus J; OPTIMAAL Investigators, et al. Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure. Am J Cardiol 2004;93:603-6.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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