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Editorials

Statins and The BMJ

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5038 (Published 07 August 2014) Cite this as: BMJ 2014;349:g5038

Rapid Response:

Re: Statins and The BMJ (Statin use in pregnancy)

Following a very intense debate in the BMJ concerning the expansion of the use of statins in low risk populations. (1)

An Independent statins review panel have called for the individual patient data to be made available for independent scrutiny. They concluded patients and their doctors need access to all relevant information to make informed decisions about their health.(2) This is never more important concerning the safe prescribing of drugs in pregnancy and those of reproductive age.

The US Food and Drug Administration currently designate statins in pregnancy as category X, or contraindicated.(3). Statins in pregnancy are also contraindicated in Europe and in many other countries worldwide. The FDA declared that the benefits of taking them do not outweigh potential risks.

A new study of statins has examined the teratogenic potential of statins (4) http://www.bmj.com/content/350/bmj.h1035

Bateman et al reason ‘As the prevalence of risk factors for cardiovascular disease, including hypercholesterolemia, diabetes, hypertension, and obesity in women of reproductive age increases (5) and as the indications for statin treatment expand, (6) it is important to understand whether it is safe to use these drugs in patients who may inadvertently become pregnant; about half of all pregnancies in the United States are unintended’. (7)

A subsequent review of the study by Haramburu et al concluded:
‘New safety data are reassuring enough about the side effects but suspension of treatment is still advisable’
Women should not take the medication if they are pregnant or planning on becoming pregnant. (8)

The Bateman statin study conducted in America included data from patients with diabetes (type unspecified) A wealth of evidence has established that cholesterol lowering statin drugs, widely used for the prevention of cardiovascular disease, do increase the risk of new-onset diabetes. (Type 2) (9)Statins have been associated with a 46% rise in type 2 diabetes risk. (10)

Those with type 2 diabetes have to have an appropriate regime to keep healthy; this regime must be immaculate within pregnancy. A good diabetic diet is a nutritious one which would be beneficial in maintaining a good lipid profile. Good health can be achieved within T2DM/gestational diabetes management without resorting to drugs unrecommended for use in pregnancy. Were the women given the option or choice of treatments/protocols which would enhance the chances of a healthy pregnancy supporting both the mother and infant? A nutritious diet is of cause vital in all women to support a healthy pregnancy. Lifestyle measures should be given more consideration as a priority, without the potential harm of barely tested prescribed drugs.

Pregnancies compromised by diabetes (types 1, 2 and gestational) are considered high risk pregnancies requiring diabetes specialist attention. This population should certainly not be a target for any medical experimentation.

Further concerns of statin use have also been highlighted that statins block the endogenous production of co-enzyme Q10 (CoQ10) (11)(12)(13)(14) Studies conducted on CoQ10 levels provide a gathering body of evidence highlighting the importance of CoQ10 in diabetes management.(15)(16)(17) Further studies in the role of co-enzyme Q10 are obviously needed.

It is interesting to note that the Bateman study suggests statins may have a therapeutic effect on pre-eclampsia. A 2009 study suggests Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. (18)

Cholesterol has been portrayed as a villain in cardiovascular health. However it holds an essential role in homeostasis. Vitamin D is Synthesized from Cholesterol and found in Cholesterol-Rich Foods.
Vitamin D is manufactured in the body from cholesterol specifically, from 7-dehydrocholesterol. (19)

Cholesterol is a precursor for other important steroid molecules: the bile salts, steroid hormones, and vitamin D. (20)

Vitamin D is also a regulator of homeostasis of bone and mineral metabolism, but it can also provide nonskeletal actions because vitamin D receptors have been found in various tissues including the brain, prostate, breast, colon, pancreas, and immune cells. (21)

Adverse reactions of statin use include a spectrum of muscle disorders including rhabdomyolysis, a form of severe myalgia. Rhabdomyolysis is a rare but clinically important adverse event of statin therapy. (21)
The FDA has reported serious liver injury with statins to be rare but unpredictable in individual patients. (23)

Past studies urged caution in using statins preconceptually and in pregnancy.

A UK 2009 study stated: “Our study examined the effects that both lipophilic and hydrophilic statins had on a key biological system that is crucial for maintaining the normal function of the placenta, which acts as the nutrient-waste exchange barrier between mother and fetus.”

They concluded: Pregnant women or those hoping to start or extend a family should talk to their physician about avoiding using the cholesterol-lowering drugs statins (24)
Another 2009 study stated ‘Given the essential role of independent cholesterol synthesis, it is not surprising that most of the known genetic defects of cholesterol biosynthesis in fetuses severely impact their development and survival.’ (25)

The cholesterol debate has captivated scientific opinion for decades. Is it not high time that all aspects of cholesterol management are discussed with all facts available to all? Prescribing of statins to pregnant women and those of reproductive age should not happen as per prescribing guidelines. There needs to be more information and awareness of avoidance of harmful substances in pregnancy. The study does not even mention loss of pregnancy through miscarriage or spontaneous abortion. (Loss of a fetus before the 20th week of pregnancy).

Cholesterol is irrefutably essential for a healthy pregnancy. Medical opinion is still divided over the role of statins and cholesterol management in general. Diet and lifestyle must be considered as a matter of priority, particularly in pregnancy. Especially in those considered high risk including those compromised by diseases such as diabetes. Statins cannot replace healthy living.. In effect medicalisation has occurred before the cradle to the grave.

(1) Godlee F. Adverse effects of statins. BMJ 2014;348:g3306
(2). www.bmj.com/content/independent-statins-review-panel-report-0
http://www.bmj.com/campaign/statins-open-data
(3).http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/WomensHealthR... Consistency of Pregnancy Labeling Across Different Therapeutic Classes. Accessed 12th April 2015.
(4) Bateman Brian T, Hernandez-DiazSonia, Fischer Michael A, SeelyEllen W, Ecker Jeffrey L, FranklinJessica M et al. Statins and congenital malformations: cohort study BMJ 2015; 350 :h1035
(5)Hayes DK, Fan AZ, Smith RA, Bombard JM. Trends in selected chronic conditions and behavioural risk factors among women of reproductive age, behavioural risk factor surveillance system, 2001-2009. Preven Chronic Dis2011;8:A120.
(6) 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. Circulation2014;129(25 Suppl 2):S1-45
(7) Edison RJ, Muenke M. Gestational exposure to lovastatin followed by cardiac malformation misclassified as holoprosencephaly. New Engl J Med2005;352:2759.
(8) Statins in pregnancy. Françoise Haramburu, Amélie Daveluy,Ghada Miremont-Salamé.BMJ 2015;350:h1484
(9) Do statins cause diabetes? Goldstein MR1, Mascitelli L. Curr Diab Rep. 2013 Jun;13(3):381-90. doi: 10.1007/s11892-013-0368-x. http://www.ncbi.nlm.nih.gov/pubmed/23456437
(10) Mayor Susan. Statins associated with 46% rise in type 2 diabetes risk, study shows BMJ 2015; 350:h1222
(11) Ellen CG Grant. Rapid response. Inevitable adverse effects due to blockage of co-enzyme Q10? http://www.bmj.com/content/348/bmj.g3306/rr/698281
(12) David L Keller Rapid response. Discussion of Dr. Grant's point regarding coenzyme Q10 http://www.bmj.com/content/348/bmj.g3306/rr/698414
(13) Sergio Stagnaro. Rapid response. Adverse effects of statins. http://www.bmj.com/content/348/bmj.g3306/rr/698206
(14) Andrew N Bamji. Rapid response. Adverse effects of statins. Http://www.bmj.com/content/348/bmj.g3306/rr/698457
(15) Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for treatment. Lamson, D.W.. Plaza S.M. Altern Med Rev, 2002. 7(2): p. 94-111.
(16) Brownlee, M., The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 2005. 54(6): p. 1615-25.
(17) CoEnzyme Q10:The State of the Science in Diabetes Ryan Bradley, ND, MPHDiabetes Action Research and Education Foundation February 2007 http://www.diabetesaction.org/site/PageServer?pagename=complementary_2_07
(18) Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Enrique Teran, Isabel Hernandez, Belen Nieto, Rosio Tavara, Juan Emilio Ocampo, Andres Calle International Journal of Obstetrics and Gynaecology. April 2009Volume 105, Issue 1, Pages 43–4
(19) The role of vitamin D in pregnancy and lactation: emerging concepts Carol L Wagner, Sarah N Taylor, Donna D Johnson, and Bruce W Hollis Womens Health (Lond Engl). 2012 May; 8(3): 323–340.
(20) Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 26.4, Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones. Available from: http://www.ncbi.nlm.nih.gov/books/NBK22339/
(21) Role of Vitamin D in Insulin ResistanceChih-Chien Sung,1 Min-Tser Liao,2 Kuo-Cheng Lu,3and Chia-Chao Wu1 Journal of Biomedicine and Biotechnology Volume 2012 (2012), Article ID 634195, 11 pages
http://dx.doi.org/10.1155/2012/634195
(22) Rhabdomyolysis and HMG-CoA reductase inhibitors. Omar MA, Wilson JP, Cox TS. Ann Pharmacother 2001;35:1096-107
(23) FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm
(24) "Statin Warning For Pregnant Women." University of Manchester. ScienceDaily. ScienceDaily, 10 December 2008. .
(25) Maternal–Fetal Cholesterol Transport in the Placenta. W Palinski. Circulation Research.2009; 104: 569-571

Competing interests: No competing interests

13 April 2015
Jane E Collis
Independent Health Researcher
None
Kenilworth Warwickshire UK