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Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 71-72  

Statins: A distant hope and thousand dangers in near

Pediatric Nephrology Ward, Sevome Shaban Hospital, Tehran, Iran

Date of Submission04-Nov-2018
Date of Decision21-Dec-2018
Date of Acceptance03-Apr-2019
Date of Web Publication20-Jul-2020

Correspondence Address:
Dr. Majid Malaki
Sevome Shaban Hospital, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpnr.JPNR_20_18

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How to cite this article:
Malaki M. Statins: A distant hope and thousand dangers in near. J Pharm Negative Results 2020;11:71-2

How to cite this URL:
Malaki M. Statins: A distant hope and thousand dangers in near. J Pharm Negative Results [serial online] 2020 [cited 2020 Aug 11];11:71-2. Available from:

Dear Sir,

Atherosclerotic Cardiovascular Disease (ASCVD) is a common cause of morbidity and mortality and can impose a high budget to all health services. The American College of Cardiology/American Heart Association (ACC/AHA) recommended the initiation of high-intensity statin therapy in patients with clinical ASCVD regardless of baseline low-density lipoprotein cholesterol (LDL-C) levels.[1] Statin, a commonly and effective therapy for dyslipidemia besides diet and exercise introduced by Merck in November 1986 as the New Drug Application to the US Food and Drug Administration (FDA) and lovastatin, was approved by FDA to become the first commercial statin in September 1987.[2]

In spite of that cardiovascular event risks can be decreased by statins Lowering LDL drugs there are opposite opinions between a cardiologist and a neurologist about standard and healthy serum LDL level because of the optimal level that mentioned by the cardiologist can be associated with hemorrhagic stroke based on the neurologist Idea. Statins can also have other neurological side effects in patients who taking statins that obligate FDA to warn about cognition disorder and memory loss following the use of statins in February 2012.[3] The association between depression, suicide, and low cholesterol level has also been known.[4] This evidence may show the reasons for a study showed in age over 60 years, LDL-C level is not associated with Cardiovascular mortality but a Low LDL level can be Linked with all-cause mortality.[5] Now, we are wandered between two ideas of using statins as a life saving drugs and others who try to show that stains should be used with cautious. One of the first studies that support stains preventive effects on cardiovascular events was published in 1995 that did not include women; they found that statins in moderate dose can decrease cholesterol level up to 20% in selected cases that reached after 6 months and remained constantly low if it be taken for 5 years regularly; they selected cases who had plasma cholesterol level in a defined range of 272 ± 23 mg/dl. They found that cardiovascular attack can be decreased only in cases who had no multiple risk factors (<2 risk factors).[6] In another study, it has been shown that maximum preventive effect of statins for coronary disease can be reached if LDL fall 24% and further decrements of LDL (up to 39%) could not be associated with a greater decrease in coronary heart disease risk, they did not address in their study what is the optimal LDL or target LDL for starting or withholding drug ?[7] In another study, it was shown that statins' treatment in cases older than 74 years without type 2 diabetes was not associated with a reduction in ASCVD or in all-cause mortality.[8] All these studies[6],[7],[8] show Statins in moderate dose in selective patients can be effective such as who had not multiple risk factors or older cases over 74 years with diabetes.

On the other side, in JUPITER study that was done in older age group included men aged over 50 years and women aged over 60 years in an unfinished trial, the authors tried to give high statin dose (rosuvastatin; 20 mg/daily) in elderly people without hyperlipidemia for a long time. In fact, it was the first of its kind, their cases were healthy persons without hyperlipidemia (LDL <130) but with elevated high-sensitivity C-reactive protein levels (CRP >2 mg/L) and authors found statins significantly reduced the incidence of major cardiovascular Effects without significant adverse event compared to placebo[9] JUPITER method may be impractical in routine clinical affairs but JUPITER provided a reason for the ACC/AHA to recommend of high-intensity statins' therapy in patients with clinical ASCVD regardless of baseline LDL cholesterol levels.[1] The well known side effects of statins are muscular ache and headache other side effects such as increased creatine phosphokinase >10 times upper limit normal and increased liver function test >3 times upper limit normal obligate us to withhold drug, there are also other adverse effects following the use of statins such as diabetes mellitus and renal dysfunction may lead to insidious and fatal acute renal failure following rhabdomyolysis or without rhabdomyolysis.[10] These side effects are so serious and wide spectrum in younger aged such as children, teenager, and young adults that are forbidden in pregnancy and breast feeding, all may be related to different biologic action of statins based on different age groups who take it because of the important role of cholesterol in growth and development of children, brain development of teenager and younger adults, cholesterol is a part of steroid hormones that play role in sexual process metabolisms and bile salt and all these show safety of a drug in adults should not be addressed to children and some specific groups.[11]

Statins' risk factors partly are related to their chemical characters; atorvastatin, lovastatin, and simvastatin are lipophilic whereas pravastatin, rosuvastatin, and fluvastatin are more hydrophilic. Lipophilic statins eliminated mainly by the bile after metabolism in the liver by CYP450 family and central nervous system complaints such as insomnia, and type 2 diabetes mellitus are more common in lipophilic statins.[12] It is amazing that in spite of our knowledge about side effects of lipophilic statins, many clinicians prescribe this type of statins. In fact, these diverse types of statins with the same effect and various side effects not only onfuse physicians for correct decision in statins' prescription but may be an obstacle for further effective research for introducing the better and less hazardous type of statins. All these considerations make us aware about factors that may increase statins' intolerance that may affect up to 15% of patients who are treated with statins. These include high-dose statin therapy, advanced age (>70 years), female sex, family history of muscle disorders, history of creatine kinase elevation, Vitamin D deficiency, renal and hepatic impairment, previous history of muscle toxicity with other lipid-lowering therapy, untreated hypothyroidism, disorders of calcium homeostasis, alcohol abuse, Asian ethnicity, low body mass index, genetic polymorphisms (e.g., genes associated with drug and muscle metabolism), surgery with severe metabolic demands, heavy and/or unaccustomed exercise, and interactions with concomitant medication.[13] In summary, statins are effective drugs for dyslipidemia, but their benefits on cardiovascular system can be achieved after 5 years of regular use while its various side effects can be seen so soon or so late, insidious or obvious forms, statins' efficacy and safety should not be addressed for all age and gender groups because of most studies have been done in middle-aged persons without focusing on many physiologic and habitual characters of cases such as alcoholic users. It can be a doubtful and dangerous policy if we just focus on LDL and cardiovascular system in a patient and instruct statins in high dose just based on their blood CRP level. It is time to believe that Newer generation statins and advertisements cannot guarantee the safety of drugs. It is time to plan a policy by cooperating of all dignitaries and experts to introduce the safe and effective type of statins drugs instead of Just focusing on the power of different types of stains for LDL lowering ability so soon before it is being late.


I dedicate this study to my leader Dr. Mohammad Mosadegh god bless his soul.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889-934.  Back to cited text no. 1
Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci 2010;86:484-93.  Back to cited text no. 2
Sahebzamani FM, Munro CL, Marroquin OC, Diamond DM, Keller E, et al. Examination of the FDA warning for statins and cognitive dysfunction. J Pharmacovigil 2014;2:141.  Back to cited text no. 3
Messaoud A, Mensi R, Mrad A, Mhalla A, Azizi I, Amemou B, et al. Is low total cholesterol levels associated with suicide attempt in depressive patients? Ann Gen Psychiatry 2017;16:20.  Back to cited text no. 4
Ravnskov U, Diamond DM, Hama R, Hamazaki T, Hammarskjöld B, Hynes N, et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: A systematic review. BMJ Open 2016;6:e010401.  Back to cited text no. 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. 6
Influence of pravastatin and plasma lipids on clinical events in the west of Scotland coronary prevention study (WOSCOPS). Circulation 1998;97:1440-5.  Back to cited text no. 7
Ramos R, Comas-Cufí M, Martí-Lluch R, Balló E, Ponjoan A, Alves-Cabratosa L, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: Retrospective cohort study. BMJ 2018;362:k3359.  Back to cited text no. 8
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr., Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.  Back to cited text no. 9
Malaki M. Statins dangers and kidney: A need for prescription revision. Transl Med 2017;7:195.  Back to cited text no. 10
Eiland LS, Luttrell PK. Use of statins for dyslipidemia in the pediatric population. J Pediatr Pharmacol Ther 2010;15:160-72.  Back to cited text no. 11
Hulisz D. Which Statin Is Right for My Patient? Medscape; 27 August, 2007.  Back to cited text no. 12
American College of Cardiology. Statin Intolerance: Not a Myth. American College of Cardiology; 2015. Available from: [Last accessed on 2018 Nov].  Back to cited text no. 13


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