Journal of Angiology & Vascular Surgery Category: Medical Type: Narrative Review

The Burning Necessity for Establishing National Guidelines - Side Effects of Lipid Lowering Drugs and Difficulty of using High Intensity Statins in Pakistani Population

Noor Dastgir1* and Wafa Qaisar2
1 Department of cardiology, Allama Iqbal Medical College, Jinnah Hospital, Lahore, Pakistan
2 Department of medicine, Akhter Saeed Medical College, Farooq Hospital, Lahore, Pakistan

*Corresponding Author(s):
Noor Dastgir
Department Of Cardiology, Allama Iqbal Medical College, Jinnah Hospital, Lahore, Pakistan
Tel:+92 3215555189,
Email:noordastgir@gmail.com

Received Date: Jan 07, 2021
Accepted Date: Feb 05, 2021
Published Date: Feb 12, 2021

Introduction

Lipid lowering strategy has been widely used in both the primary as well as the secondary prevention of atherosclerotic cardiovascular disease, particularly in managing patients who are either diagnosed with ischemic heart disease or stroke or face great susceptibility to developing these complications as a result of risk factors like diabetes, hypertension, sedentary lifestyle and so on [1,2]. 

The mechanism of action of Statins is by inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase which is the rate-limiting step in cholesterol synthesis [3]. Statins hence have a great impact on the lipid metabolism and play a vital role in prevention of atherosclerotic complications [4]. They reduce LDL-C, Total cholesterol, and Triglyceride levels; slightly increase HDL-C levels [5]; and are also thought to have anti-inflammatory and other plaque stabilization effects, referred to as their pleiotropic properties [6]. 

The updated guideline on the use and dosing of statins was issued in 2013 by the American College of Cardiology (ACC) and the American Heart Association (AHA) where a classification was devised categorizing therapy into low, medium and high intensity therapy stating fixed doses, and clear indications as to which patients would be benefitted by which group [7,8]. 

High intensity statin therapy hopes to achieve LDL reductions of more than 50% of the baseline and mainly includes Atorvastatin (40-80mg) and Rosuvastatin (20-40mg) [9]. While all the benefits of lipid lowering therapy cannot be emphasized upon enough, it does bring out the question of challenges in compliance to treatment regimens comprised of such high doses owing to the side effects being experienced by the patients [10,11]. 

Statins may cause widespread systemic effects like hepatotoxicity, type 2 diabetes, cataract, polyneuropathy, memory loss, behavioral changes and, rarely, headache, gastrointestinal disturbance, rash etc [12]. 

Most common concerning consequences of statin therapy include musculoskeletal system involvement in the form of myopathy and tendinopathy that may present with muscle aches (myalgias) and sometimes even leading to muscle breakdown (rhabdomyolysis) causing elevated creatinine kinase levels with a pathophysiology not completely understood [13-16]. 

Studies done previously have reported that muscle and tendon related side effects were most commonly noticed in patients treated with rosuvastatin. The onset of myalgias may be variable ranging from a few weeks after treatment initiation to years. Older age, female gender, individual patient genetics and comorbid conditions like hypertension, diabetes and hypothyroidism are all factors that may increase the prevalence of such effects along with processes at molecular level like the CYP mediated statin metabolism and various drug-drug interactions [17,18]. 

In view of this, FDA recommends lowest effective dose of statins to reduce statin-associated myopathies and other untoward outcomes accompanying their use [19]. 

Inter-racial differences in response to statins have been previously reported [20]. Asian patients have been seen to have a mounted response compared to the Caucasian population due to differences in ethnicity and the genetic make-up affecting the metabolism [21]. In one such study, it was seen in the Japanese population that a lower dose of statins demonstrated similar relative risk reduction of cardiovascular events to a higher dose of statins in Western patients [22,23]. In fact, the maximum dose of atorvastatin in clinical practice was 40 mg per day in Japan, while the dose is 80 mg per day in the United States [24]. Most adverse effects of statins are dose related and in a directly proportional relationship [25]. 

It is important to understand that Pakistani patients may have a lower threshold for tolerance of statin therapy while at the same time, they may require perhaps a lower dose to achieve target levels of LDL. In a study conducted at Agha Khan University, it was concluded that even an alternate day regimen may have similar clinical benefits to standard daily dosing but with better tolerance and compliance [25]. 

Several studies have been done internationally studying the difficulties health care providers face while ensuring adherence to high dose statin therapy. We wish to explore the possibility of establishing these interracial differences in response to statin therapy, both in achieving the therapeutic goals as well the occurrence of intolerable side effects that may lead to discontinuation of medication despite clear clinical benefits. Hence it is important to emphasize the need of developing national guidelines keeping in mind our population regarding statin therapy.

References

  1. Harrison TN, Scott RD, Cheetham TC, Chang SC, Hsu JY, et al. (2018) Trends in statin use 2009-2015 in a large integrated health system: pre- and post-2013 ACC/AHA guideline on treatment of blood cholesterol. Cardiovasc Drugs Ther 32: 397-404.
  2. European Association for Cardiovascular Prevention & Rehabilitation; Reiner Z, Catapano AL, De Backer G, Graham I, et al. (2011) ESC/EAS Guidelines for the management of dyslipidaemias . The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 32: 1769-1818.
  3. Hess CN, Low Wang CC, Hiatt WR (2018) PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Annu Rev Med 69: 133-145.
  4. Rosenson RS (2004) Statins in atherosclerosis: Lipid-lowering agents with antioxidant capabilities. Atherosclerosis 173: 1-2.
  5. Istvan ES, Deisenhofer J (2001) Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292: 1160-1164.
  6. Oesterle A, Laufs U, Liao JK (2017) Pleiotropic effects of statins on the cardiovascular system. Circulation research 120: 229-243.
  7. Chou R, Dana T, Blazina I, Daeges M, Bougatsos C, et al. (2016) Statin Use for the Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force [Internet].
  8. García-Gil M, Blanch J, Comas-Cufí M, Daunis-i-Estadella J, Bolíbar B, et al. (2016) Patterns of statin use and cholesterol goal attainment in a high-risk cardiovascular population: A retrospective study of primary care electronic medical records. J Clin Lipidol 10: 134-142.
  9. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, et al. (2012) European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 33: 1635-1701.
  10. Jacobson TA (2014) NLA task force on statin safety-2014 update. J Clin Lipidol 8: 1-4.
  11. Krüger K, Leppkes N, Gehrke-Beck S, Herrmann W, Algharably EA, et al. (2018) Improving long-term adherence to statin therapy: a qualitative study of GPs’ experiences in primary care. British Journal of General Practice 68: 401-407.
  12. Beltowski J, Wojcicka G, Jamroz-Wisniewska A (2009) Adverse effects of statins-mechanisms and consequences. Current drug safety 4: 209-28.
  13. Scott RS, Lintott CJ, Wilson MJ (1991) Simvastatin and side effects. New Zealand Medical Journal 104: 493-495.
  14. Cham S, Evans MA, Denenberg JO, Golomb BA (2010) Statin-associated muscle-related adverse effects: a case series of 354 patients. Pharmacotherapy 30: 541-553.
  15. Nikolic D, Banach M, Chianetta R, Luzzu LM, Pantea Stoian A, et al. (2020) An overview of statin-induced myopathy and perspectives for the future. Expert Opin Drug Saf 19: 601-615.
  16. Golomb BA, Evans MA (2008) Statin adverse effects : A review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs 8: 373-418.
  17. Thompson PD, Panza G, Zaleski A, Taylor B (2016) Statin-associated side effects. J Am Coll Cardiol 67: 2395-410.
  18. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, et al. (2015) Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 36: 1012-1022.
  19. Murakami H, Sakaeda T, Kadoyama K, Okuno Y (2013) Gender effects on statin-associated muscular adverse events: an analysis of the FDA AERS database. Pharmacol Pharm 4: 340-346.
  20. Naito R, Miyauchi K, Daida H (2017) Racial differences in the cholesterol-lowering effect of statin. J Atheroscler Thromb 24: 19-25.
  21. Lee E, Ryan S, Birmingham B, Zalikowski J, March R, et al. (2005) Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther 78: 330-334.
  22. Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, et al. (2006) Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 368: 1155-1163.
  23. Nagar SP, Rane PP, Fox KM, Meyers J, Davis K, et al. (2018) Treatment patterns, statin intolerance, and subsequent cardiovascular events among Japanese patients with high cardiovascular risk initiating statin therapy. Circulation Journal 82: 1008-1016.
  24. Naito R, Miyauchi K, Daida H (2017) Racial Differences in the Cholesterol-Lowering Effect of Statin. J Atheroscler Thromb 24: 19-25.
  25. Abdul Muhammad Z, Ahmad T, Baloch N (2019) Can alternate-day Statin regimen minimize its adverse effects on muscle and tendon? A systematic review. J Pak Med Assoc 69: 1006.

Citation: Dastgir N, Qaisar W (2021) The Burning Necessity for Establishing National Guidelines - Side Effects of Lipid Lowering Drugs and Difficulty of Using High Intensity Statins in Pakistani population. J Angiol Vasc Surg 6: 059.

Copyright: © 2021  Noor Dastgir, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Herald Scholarly Open Access is a leading, internationally publishing house in the fields of Sciences. Our mission is to provide an access to knowledge globally.



© 2024, Copyrights Herald Scholarly Open Access. All Rights Reserved!