SUMMARY

It appears that the adverse effects of statins are being used as a smokescreen to avoid the debate over its lack of effect in primary prevention. The ultimate intention is likely to change the line of independence of the British Medical Journal, to change its editor and to promote industrial interests.

Statins

The statins are drugs which limit cholesterol synthesis by inhibiting HMG – CoA reductase.

Like all drugs, statins have precise indications.

Statins, like all medications, have potential for adverse effects.

Benefits and harms

Like all drugs, statins produce benefits in some cases but all patients are subject to the risk from its harms and its adverse effects.

This is because, in general, the harms occurs in a fixed proportion of the patients that receive treatment, while the benefits depend on the number of patients «who need» the medication after being diagnosed and treated.

Therefore, it is those patients who have been prescribed correctly and comply with treatment that reap the benefits.

The risk of incurring in harm and adverse effects concerns all patients that are prescribed statins, whether appropriately or not, and that comply with treatment.

Statins indications

Statins should be used in those cases where its expected benefits exceed its likely harms.

Statins are effective in secondary prevention For example, in patients that have suffered a myocardial infarction.

Statins have dubious benefits in primary prevention (in patients who so not have any cardiovascular problem but have risk factors such as «high cholesterol «, are smokers, belongs to low social class, have diabetes, etc). Some clinical trials suggest that statins may have some benefit in patients with «high cardiovascular risk,» but there is no agreement on the «intensity» of such cardiovascular risk or about the beneficial effect in itself.

Statins and primary prevention in the British Medical Journal

The British Medical Journal published two studies in 2013 (1,2) , on the effect of statins in primary prevention and both concluded that there was no benefit in those who had a low cardiovascular risk (less than 20 % at 10 years). To highlight the absurdity of employing statins, an observational study about statins was cited which showed that intolerance to treatment with statins affected 18-20% of patients (3).

Later on, the two studies were corrected, as the percentage of intolerance was actually 18% in the observational study, but figures could not be extrapolated as this percentaje was “substantially higher than the 5% to 10% usually described in randomized, placebo-controlled, clinical trials».

Adverse effects of statins

The problem is that we do not know the real figure regarding harms and adverse effects caused by statins. The harms probably affect 9%, even if whether 20% have myalgia and myopathy (4). Muscle adverse effects are the most reported problem both in the literature and by patients; include muscle pain, fatigue and weakness as well as rhabdomyolysis (5).

In fact, studies about the safety of statins only started being carried out in 2002, after the rhabdomyolisis deaths caused by cerivastatin (6). These are studies that should take into account the situations in clinical practice in which statins are taken (along with other drugs, with several diseases, age groups not included in the clinical trials, etc).

The issue is more complicated because of the lack of access to the raw data from the clinical trials, and its funding by Pharma. In many occasion side effects data is collected in clinical trials but not reported in the scientific papers. The German governments’ cost effectiveness agency found complete information for 87% of adverse event outcomes in documents of the industry but only 26% in the journal publications (7).

The British Medical Journal under attack

The British Medical Journal depends on the British Medical Association.

The British Medical Journal has always stood for independence, and in recent times is taking an active part, for example, in the # AllTrials movement that promotes access to all the raw data from clinical trials. It has also helped Cochrane Reviews in the analysis of the antivirals Tamiflu and Relenza (which are useless and cause side effects). It promotes and helps the «Overdiagnosis» campaign that includes, for example, criticizing the lack of efficacy of breast cancer screening with mammography. It has facilitated the publication of, for example, studies about the excesses around ADHD. The British Medical Journal is independent from the pharmaceutical and technology industries, whom it dislikes, irritates and bothers. It is therefore not surprising that the President of the Cholesterol Treatment Trialists ‘ Collaboration CTT) visits the editor of the British Medical Journal ( BMJ) to ask for the retraction of the two articles about primary prevention of cholesterol due to the error about the harms of statins (8). It is the CTT against BMJ, and more.

Without delving into the scientific debate, the President of CTT approached the tabloid press, which has in turn attacked the British Medical Journal as if the problem was about discussing the rate of the adverse effects of statins.

To retract or not to retract

The problem is that statins have no use in primary prevention, particularly in patients with a low risk. In these patients, prescribing and monitoring statin treatment is unethical, as «a drug that is not necessary and is used in a situation that is not justified under any circumstances, does not compensate is harms with potential benefits in cases in causing adverse effects».

The British Medical Journal agreed to correct the figure regarding the adverse effects, but does not intend to retract the two articles. In scientific journals, retraction of articles occurs in situations of fraud or misconduct (9). In fact the British Medical Journal has decided that the right thing to do is to pass this decision to an independent panel.

The members of the Cholesterol Treatment Trialists ‘ Collaboration have in many cases strong relationships with industry. They also don’t have access to the raw data from clinical trials, which industries do not share, and therefore do not know the percentages of adverse effects, except for the published summaries.

It appears that the adverse effects of statins are being used as a smokescreen to avoid the debate over its lack of effect in primary prevention.

Far from the scientific debate

The campaign against the British Medical Journal may be included in an intense campaign that is even changing the new and positive attitude of the European Medicines Agency to fulfill the mandate of the Parliament of the European Union to grant free access to the raw data of clinical trials.

As such, the attack on the British Medical Journal is far from the scientific debate. The ultimate intention is likely to change the line of independence, to change the editor and to promote industrial interests.

The least problem is the rate of adverse effects of statins; a bigger problem is its lack of effectiveness. Without neglecting such adverse effects, which can be deadly and the hundreds of deaths caused by cerivastatin just over a decade demonstrated that.

The attack on the British Medical Journal is the least problem; a bigger problem is the loss of independence of a scientific journal.

We should follow this saga because we played a lot in it.

By Juan Gérvas, MD, PhD, retired general practitioner , Equipo CESCA (Madrid , Spain) jjgervas@gmail.com @ JuanGrvas www.equipocesca.org

Bibliography

1. Abramson JD, Rosenberg HD, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ2013;347:f6123.
2. Malhotra A. Saturated fat is not the major issue.BMJ2013;347:f6340
3. Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings. Ann Intern Med2013;158:526-34.
4. Grundy SM. Statin discontinuation and intolerance: the challenge of lifelong therapy. Ann Intern Med 2013;158:562-3.
5. Golomb BA, Evans MA. Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism. Am J Cardiovasc Drugs. 2008; 8(6): 373–418.
6. Gérvas J, Pérez Fernández M. Cerivastatin and fatal rhabdomyolisis: not just a safety issue. Healthy Skepticism International News. 2002;20 (2) http://www.healthyskepticism.org/global/news/int/hsint2002-06
7. Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervölgyi V, Kohlepp P, et al. Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data. PLoS Med. 2013 Oct 8;10(10):e1001526.
8. Godlee I. Adverse effects of statins. BMJ 2014;348:g3306 http://www.bmj.com/content/348/bmj.g3306
9. Committee on Publication Ethics. Retraction guidelines. http://publicationethics.org/files/retraction%20guidelines.pdf

To know more

Prof Sir Rory Collins told the Guardian in March that a paper and a subsequent article in the BMJ were inaccurate and misleading. http://www.theguardian.com/society/2014/may/15/statins-bmj-statement-professor-collins-side-effects

Statins row: Critics are biased, says doctor [Malhotra] who warned of drugs’ side-effects. http://www.independent.co.uk/life-style/health-and-families/health-news/statins-row-critics-are-biased-says-doctor-who-warned-of-drugs-sideeffects-9388337.html

Rapid answers to the BMJ editorial http://www.bmj.com/content/348/bmj.g3306?tab=responses

Ben Goldacre’ post «statins side effects» http://www.theguardian.com/science/blog/2014/mar/14/statins-side-effects-study-placebo-ben-goldacre

Going deep to data access and money (and power). It’s not about statins. It’s about censorship. http://www.zoeharcombe.com/blog/

Clinical trials systematically get the wrong answer, especially on adverse events. They are the gold standard way to hide adverse events. http://davidhealy.org/fucked/

From BMJ blog http://blogs.bmj.com/bmj/2014/05/19/the-bmj-today-statins-and-the-bmj/

From Forbes, panel members http://www.forbes.com/sites/larryhusten/2014/05/19/bmj-names-panel-members-to-review-disputed-statin-articles/

Going deep to data access and money (and power). It’s not about statins. It’s about censorship. http://www.zoeharcombe.com/blog/

As a class, adverse events associated with statin therapy are not common. Statins are not associated with cancer risk but do result in a higher odds of diabetes mellitus. Among individual statins, simvastatin and pravastatin seem safer and more tolerable than other statins. http://www.ncbi.nlm.nih.gov/pubmed/23838105