Comparative Study of Rosuvastatin as Monotherapy Versus Rosuvastatin with Ramipril in Dyslipidemia and Their Effects on Atherosclerosis

Kumar Raj^1, , Garg Ravinder², Aggarwal Simmi³, Kohli Kamlesh¹ and Misra Gansham⁴

¹Department of Pharmacology, Guru Gobind Singh Medical College and Hospital (Baba Farid University of Heath Sciences), Faridkot -151203, INDIA

²Department of Medicine, Guru Gobind Singh Medical College and Hospital (Baba Farid University of Heath Sciences), Faridkot -151203, INDIA

³Department of Radiodiagnosis, Guru Gobind Singh Medical College and Hospital (Baba Farid University of Heath Sciences), Faridkot -151203, INDIA

⁴Department of Social and Preventive Medicine, Guru Gobind Singh Medical College and Hospital (Baba Farid University of Heath Sciences), Faridkot -151203, INDIA

Cite this paper:
Kumar Raj, Garg Ravinder, Aggarwal Simmi, Kohli Kamlesh and Misra Gansham. Comparative Study of Rosuvastatin as Monotherapy Versus Rosuvastatin with Ramipril in Dyslipidemia and Their Effects on Atherosclerosis. American Journal of Medical Sciences and Medicine. 2014; 2(3):58-63. doi: 10.12691/ajmsm-2-3-2

Abstract

Objective: To evaluate the effect of Rosuvastatin as monotherapy versus combination therapy of Rosuvastatin with Ramipril on the Intimo-Media Thickness (IMT) of the carotid arteries in patients of dyslipidemia. Background: Statins have shown to improve the lipid profile in dyslipidemic patients. These have anti-oxidative and anti-inflammatory actions. The statins may have also antiatherosclerotic action. Angiotensin converting enzyme (ACE) inhibitors have shown to prevent the development of atherosclerosis in animal models. This antiatherosclerotic effects of ACE inhibitors is due to their multitask actions viz. ACE inhibition, antiproliferative action as well as inhibitory to the smooth muscle cell accumulation at the site of atherosclerotic lesion. Method: 88 patients of newly diagnosed dyslipidemia, aged 30-70 years, were randomized into two groups. Group I, was allocated Rosuvastatin (as monotherapy) and Group II, Rosuvastatin with Ramipril (Combination therapy). Patients were assessed at baseline, 6 weeks and 12 weeks for carotid arteries for IMT and plaque size by B-mode ultrasound, and other parameters were also assessed. Results: In group I and group II, mean percentage change in TC, LDL, TG and HDL was highly significant (p<0.001) in both the groups while no significant change was seen between the groups at 12 weeks. Mean percentage change in mean IMT and plaque size were +0.01224% (p>0.05) versus -0.0704% (p>0.05) and +0.006% (p>0.05) versus -4.554% (p>0.05) respectively in group I and group II at 12 weeks while these changes were statistically insignificant between both the groups. Mean IMT and Plaque size reduction were more in group II. Conclusion: Both the therapies effectively improved the lipid profile in dyslipidemic patients. But combination therapy of Rosuvastatin with Ramipril reduces IMT and plaque size more than the rosuvastatin monotherapy. This shows that antiatherosclerotic action of combination therapy occurs due to its action on different risk factors of atherosclerosis.

Keywords:
anti-atherosclerotic Intimo-Media Thickness (IMT) plaque statins Angiotensin Converting Enzyme (ACE) inhibitor Total Cholesterol (TC) Triglyceride (TG) Low Density Lipoprotein (LDL) High Density Lipoprotein (HDL) combination therapy

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References:

[1]	Libby P. The Pathogenesis of Atherosclerosis. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL editors. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005. p. 1425-1430.
[2]	National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panal III). Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, Evalution, and Treatment of High Blood Cholesterol in adults (Adult Treatment Panal III) final report. Circulation, 2002, 106, 3143-3421.
[3]	World Health Organisation. Non-communicable diseases. Cardiovascular diseases (CVD). 2014; [1 Screen]. Available at: URL:http://:www.who.int/mediacentre/factsheets/fs317/en/#. [Accessed May 10, 2014.
[4]	Magyar MT, Paragh G, Katona E, Valikovics A, Seres I, Csiba Laszlo, et al., “Serum Cholesterol Have a More Important Role Than Triglycerides in Determining Intima- Media Thickness of the Common Carotid Artery in Subjects Younger Than 55 Years of Age”, J Ultrasound Med, 23, 1162-69, 2004.
[5]	Herder M, Arntzen KA, Johnson SH, Mathiesen EB, “The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromso study”, Cardiovascular Diabetology, 2012; 11: 77. Available at http://www.cardiab.com/content/11/1/77
[6]	Valduza JM,Schreiber SJ, Roehl JZ, Klingebeil R. Neurosonology and Neuroimaging of stroke. Stugart:Ed.Theme.2008.
[7]	Touboul PJ, Hennerici MG, Meirs S, Adams H, Amarenco, Bornstein P, et al. “Mannheim Carotid Intima-Media Thickness Consensus (2004-2006)”, Cerebrovasc Dis, 23, 75-80, 2007.
[8]	Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M, “Predication of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis”, Circulation, 115 (4), 459-67, 2007.
[9]	Nohara R, Daida H, Hata M, Kaku K, Kawamori R, Kishimoto J, et al., “Effects of Long-Term Intensive Lipid Therapy With Rosuvastatin on Progression on Progression of Carotid Intmia-Media Thickness”, Circulation Journal, 77, 1526-33, 2013.
[10]	Crouse JR, Raichlan JS, Riley WA, Evans GW, Palmer MK, O’Leary DH et al., “Effect of Rosuvastatin on Progression of Carotid Intima-Media Thickness in Low-Risk Individuals With Subclinical Atherosclerosis-The METEOR Trial”, JAMA, 297 (12): 1344-52, 2007.
[11]	Yamazaki D, Ishida M, Watanable H, Nobori K, Oguma Y, Terata Y, “Comparison of anti-inflammatory effects and high- density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe”, Lipids in Health and Disease, 12: 9, 2013. Available: http://lipidworld.com/content/12/1/9
[12]	Mok CC, Wong KW, To CH, Lai JPS, Lam CS, “Effects of Rosuvastatin on Vascular Biomarkesr and Carotid Atherosclerosis in Lupus: A Randomized, Double-Blind, Placebo-Controlled Trial”, Arthritis Care and Research, 63 (6), 875-83, 2011.
[13]	Munzel T, Keaney F, Are ACE Inhibitors a “Magic Bullet” Against Oxidative stress? Circulation, 104, 1571-74, 2001.
[14]	Lonn EM, Yusuf S, Dzavik V, Smith S, Moore-Cox A, Riley WA, et al., “Effects of Ramipril, and Vitamin E on Atherosclerosis-The Study to evaluate Carotid Ultrasound Changes in Patients reated with Ramipril and Vitamin E (SECURE)”, Circulation, 103, 919-25, 2001.
[15]	Wolffenbuttel BHR, Franken AAM, Vincent HH, “Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes- CORALL study”, Journal of Internal Medicine, 257, 531-539, 2005.
[16]	Jayaram S, Jain MM, Naikawdi AA, Gawde A, Desai A, “Comparative Evaluation of the Efficacy, Safety and Tolerability of Rosuvastatin 10 mg with Atorvastatin 10 mg in Adult patients with hypercholesterolaemia: The First Indian Study”, Journal of The American Medical Association, 102, 48-52, 2004.
[17]	Shepherd J, Packard C, Littlejohn Ill TW, Walker J, Stein EA, “Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy”, Current Medical Research Opinion, 20 (10), 1571-1578, 2004.
[18]	MacMohan S, Sharpe N, Gamble G, Clague A, Mhurchu CN, Clark T, et al., “Randomized, Placebo-Controlled Trial of the Angiotensin-Converting Enzyme Inhibitors, Ramipril, in Patients With Coronary or Other Occlusive Arterial Disease”, Journal of The American College of Cardiology, 36 (2), 438-443, 2000.
[19]	Andersen K, Weinberger MH, Egan B, Constance CM, Wright M, Lukashevich et al., “Comparative Efficacy of Aliskiren Monotherapy and Ramipril Monotherapy in Patients with stage 2 Systolic Hypertension: Subgroup Analysis of a Double-blind, Active Comparator Trial”, Cardiovascular Therapeutics, 28: 344-49, 2010.
[20]	Soni U, Moghe VV, Jain P, Upadhyaya P, “A Comparative Study of Efficacy and Tolerability of Telmisertan and Ramipril”, International Journal of Pharma Sciences, 3 (3): 240-43, 2013.