Statins can increase the risk of shingles infection

This study was published in the European Journal of Clinical Microbiology and Infectious Diseases 2015 Jul;34(7):1451-8

Study title and authors:
Statins can increase the risk of herpes zoster infection in Asia.

Chen HH, Lin CL, Yeh CJ, Yeh SY, Kao CH.
Institute of Medicine and Public Health, Chung Shan Medical University, Taichung, Taiwan.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25864192

This study evaluated whether statin therapy increases the risk of herpes zoster (shingles). The study included 53,069 patients receiving statin therapy and 53,069 patients without statin therapy who were followed for more than 4.5 years.

The study found:
(a) Patients taking statins had a 21 % higher risk of contracting shingles than the patients not taking statins.
(b) Patients taking higher dose statins had more than 150% higher risk of contracting shingles than the patients not taking statins.

Chen concluded: "Statin therapy can increase herpes zoster (shingles) infection."

 

Links to other studies:

13 year study of nearly one million individuals shows that statins significantly increase the risk of shingles in older people

Doctor says statin drug hypersensitivity reactions are potentially life-threatening

Statins may be associated with skin lesions

Carbohydrate, Sugar, and Obesity in America

We like explanations that are simple, easy to understand, and explain everything.  One example of this is the idea that eating carbohydrate, or sugar, is the primary cause of obesity.  This lets us point our finger at something concrete and change our behavior accordingly.  And it's true enough that it has practical value.  But the world around us often turns out to be more complex than we'd like it to be.

The CDC recently released its latest data on the prevalence of obesity in the US, spanning the years 2013-2014 (1).  These data come from its periodic National Health and Nutrition Examination Surveys (NHANES).  Contrary to what many of us had hoped for after a slight decline in obesity in the last survey, the prevalence has once again increased.  Today, roughly 38 percent of US adults have obesity.  As a nation, we're continuing to gain fat, which is extremely concerning.

I decided to examine the relationship between obesity prevalence and our intake of carbohydrate and sugar over the years.  The food intake data come from the USDA's Economic Research Service (2).  For some reason, the data on carbohydrate don't extend beyond 2010.  This probably relates to funding cuts at the USDA*.

Let's have a look at the data for carbohydrate:

Read more »

Cardiac surgery patients taking statins have a 42% increased risk of death

This study was published in the Journal of Cardiothoracic Surgergy 2012 Jul 13;7:39

Study title and authors:
Hemodynamic effects of peri-operative statin therapy in on-pump cardiac surgery patients.

Hinz J, Gehoff P, Schotola H, Hosseini MT, Didilis VN, Jebran AF, Gehoff A, Wiese CH, Schulz EG, Schoendube FA, Popov AF.
Department of Anaesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22533985

This study set out to investigate the effect of statin therapy on patients undergoing cardiac surgery with cardiopulmonary bypass. (Cardiopulmonary bypass is a technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the body). The study included 478 patients who stayed in hospital for an average of 25 days. They were divided into (i) statin taking group (ii) non statin group.

The study found:
(a) Patients taking statins had a 42% increased risk of death whilst in hospital compared to patients not taking statins.
(b) The statin taking group had a significant 16% lower Systemic Vascular Resistance Index compared to the non statin group. (A decrease of Systemic Vascular Resistance Index is evidence for systemic inflammation).

  

Links to other studies:

Statin treatment is associated with a higher death rate and a higher risk of heart attack in angioplasty patients

Statins can damage the lining of blood vessels

Statin major adverse effects have been under-reported and the way in which they withheld from the public, and even concealed, is a scientific farce 



Dr finds that statins do not help diabetics and official guidelines regarding statin use should be re-examined and reformulated by experts independent from the pharmaceutical industry

This paper was published in Reviews on Recent Clinical Trials 2012 May;7(2):150-7

Study title and authors:
Is the use of cholesterol-lowering drugs for the prevention of cardiovascular complications in type 2 diabetics evidence-based? A systematic review.

de Lorgeril M, Hamazaki T, Kostucki W, Okuyama H, Pavy B, McGill AT, Rabaeus M.
Laboratoire Coeur & Nutrition, Université Joseph Fourier-CNRS, Faculté de Médecine, 38706 La Tronche, France. michel.delorgeril@ujf-grenoble.fr

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22353198

This paper systematically reviewed the results of high-quality double blind trials testing whether cholesterol-lowering drugs (statins and fibrates) reduce mortality and cardiovascular complications specifically in type two diabetics.

The review of the scientific literature found four trials, three statin and one fibrate.
(a) Statin trials:
(ai) The Collaborative Atorvastatin Diabetes Study (CARDS) trial was discontinued 2 years before the anticipated end and in the absence of significant effect on both overall and cardiovascular mortality, suggesting that the trial should not have been prematurely stopped.
(aii) The Deutsche Diabetes Dialyse Studie (4D) trial showed no significant effect on heart attack, stoke or cardiovascular and overall death rates.
(aiii) The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) trial showed no significant effect in nonfatal heart attacks, nonfatal stroke, coronary artery bypass surgery, resuscitated cardiac arrest, worsening or unstable angina requiring hospitalization or cardiovascular and overall death rates.
(b) Fibrate trial: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial showed no significant effect on coronary heart disease death, non-fatal heart attack or death rates.

Dr de Lorgeril concluded: "This review does not support the use of cholesterol-lowering drugs (such as statin and fibrate) to reduce mortality and cardiovascular complications in type two diabetics. Official guidelines should be re-examined and reformulated by experts independent from the pharmaceutical industry".



Review reveals statins only extend life by 3 or 4 days. Closer analysis finds they may actually shorten life.

This study was published in the BMJ Open 2015 Sep 24;5(9):e007118

Study title and authors:
The effect of statins on average survival in randomised trials, an analysis of end point postponement.

Kristensen ML, Christensen PM, Hallas J.
Department of Clinical Pharmacology, University of Southern Denmark, Odense, Denmark.

This can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26408281

The objective of the study was to estimate the average postponement of death by statin users in statin trials. The study included an analysis of 11 trials that were defined by being randomised, having at least 1000 patients included, comparing a statin with no treatment or placebo, having at least two years of follow-up. Six of the studies were for primary prevention and five for secondary prevention with a follow-up between 2.0 and 6.1 years.

The analysis found:
(a) In primary prevention trials statin users lived an extra 3.2 days.
(b) in secondary prevention trials statin users lived an extra 4.1 days.

So the results show that - with the massive expense of buying the drugs, with the plethora of debilitating side effects, such as diabetes, muscle damage, heart failure, suicide, homicide, accidental death, cognitive impairment, Alzheimer's, dementia, birth defects, cancer, cataract, erectile dysfunction, fatigue, liver damage, lung disease, memory loss, pancreatitis, peripheral neuropathy, rhabdomyolysis, and many, many more - with all these toxic side effects statins may (supposedly) increase your life by only three of four days.

However, do they even prolong life by this paltry amount?

Clinical trials with statins are performed in highly selected populations. Most statin trials have exclusion criteria that screens out a significant percentage of people because of health and toxicity concerns. This has the effect of making the statin drugs look better than they actually are.

In the real world, few people are discouraged from using statins by the medical profession, so many people who would not be allowed in the clinical trials are taking statin drugs. This is why clinical trials show that side effects are suffered by about 5% of participants, yet in reality the figure can be anything from a fifth to over two thirds (or even more) of all statin users. 

The begs the question, that if more people suffer toxic side effects than the clinical trials portray, then do people who are taking statin drugs also have a shorter life?

In trying to determine an answer to this question it may be helpful to look at the exclusion criteria in the eleven trials in this study.

The eleven trials were:
ALLHAT
ASCOT
CARDS
JUPITER
MEGA
WOSCOPS
4S
GISSI-HF
GISSI-P
LIPID
CORONA

(1) Exclusion criteria for the ALLHAT trial:
(i) People intolerant of statins: It's anyone's guess what this number is.
(ii) Those with liver or kidney disease.
(iii) Other contraindications for statin therapy: This may include hypothyroidism; pregnancy; lactation; excess alcohol intake; use of drugs such as: amiodarone, verapamil, diltiazem, erythromycin, clarithromycin, ciclosporin, itraconazole, ketoconazole, HIV protease inhibitors, nefazodone and ciclosporin; consumption of grapefruit or grapefruit juice; use of warfarin; patients at risk of haemorrhagic stroke.
(iv) Secondary cause of hyperlipidemia: This may include patients with diabetes; hypothyroidism; nephrotic syndrome; renal failure; use of drugs such as; adrenal steroids, isotretinoin, thiazides, anticonvulsants, oral contraceptives and alcohol; those who have obstructive liver disease, hepatitis, gaucher disease, von Gierke disease, acute intermittent porphyria, anorexia nervosa, systemic lupus erythematosus; the obese and those who smoke cigarettes. 

(2) Exclusion criteria for the ASCOT trial:
(i) Patients who had had a previous heart attack.
(ii) Those with angina.
(iii) A stroke within the previous 3 months.
(iv) Fasting triglycerides higher than 4·5 mmol/L.
(v) Heart failure.
(vi) Uncontrolled arrhythmias.
(vii) Anyone with a haematological (blood) or biochemical (chemical substances and vital processes) abnormality. 

(3) Exclusion criteria for CARDS:
(i) Any past history of myocardial infarction, angina, coronary vascular surgery, cerebrovascular accident, or severe peripheral vascular disease.
(ii) Abnormal kidneys.
(iii) High blood sugar.
(iv) Those who take their drugs less than 80% of the time.

(4) The JUPITER trial:
(i) 89,890 patients were screened for the study; (only 17,802 patients were finally entered into the trial.)
(ii) 37,611 patients were excluded because their LDLcholesterol was more than 130 mg/dL.
(iii) 25,993 because their C-reactive protein was less than 2.0 mg/L.
(iv) 957 patients for diabetes.
(v) 349 patients for hypothyroidism.
(vi) 305 patients for liver disease.
(vii) Many others for hypothyroidism, hypertriglyceridemia, concurrent use of hormone replacement therapy, or cancer in the last 5 years before enrolment
(viii) Additionally, 3,948 patients withdrew consent.
(ix) An additional 1,521 patients were excluded later after a 4-week placebo run-in for poor compliance.
(x) Despite all the scrutiny in choosing patients for the JUPITER trial, at the time of study termination, only 75% of study participants were still taking their study medication.

(5) The MEGA trial:
(i) 15,210 patients entered a 4-week run in phase, but 7,201 (48%) were excluded and only 8,009 finally participated in the trial.
(ii) Reasons for exclusion included: lack of effect on cholesterol, kidney and liver disease: and because "the patient had little probability of complying with the treatment".

(6) Exclusion Criteria for the WOSCOPS trial:
(i) History of treated heart attack.
(ii) Hospitalization for angina within prior 12 months.
(iii) Electrocardiogram abnormalities,.
(iv) Arrhythmia.
(v) Frequent premature ventricular contractions.
(vi) More than 2nd degree atrioventricular Block.
(vii) High blood pressure.
(viii) History of rheumatic heart disease.
(ix) Congenital heart disease.
(x) Cor pulmonale, chronic bronchitis, emphysema, or kyphoscoliosis associated with EKG changes.
(xi) Cardiomegaly, congestive cardiac failure, or significant valvular heart disease.
(xii) Other suspected serious physical illness.
(xiii) Psychiatric illness.
(xiv) Laboratory exclusions.

(7) 4S trial exclusion criteria:
(i) Premenopausal women of childbearing potential.
(ii) Secondary hypercholesterolaemia (see ALLHAT (iv)).
(iii) Unstable or Prinzmetal angina, tendon xanthomata.
(iv) Planned coronary artery surgery or angioplasty.
(v) Heart attack during the preceding six months.
(vi) Antiarrhythmic therapy.
(vii) Congestive heart failure requiring treatment.
(viii) Persistent atrial fibrillation.
(ix) Cardiomegaly.
(x) Haemodynamically important valvular heart disease.
(xi) Stroke.
(xii) Impaired liver function.
(xiii) Partial ileal bypass.
(xiv) History of drug or alcohol abuse.
(xv) Poor mental function.
(xvi) Other serious disease.
(xvii) Intolerant of statins.

(8) The GISSI-HF exclusion criteria:
(i) Heart attack, unstable angina or revascularization procedure within 1 month.
(ii) Planned cardiac surgery, expected to be performed within 3 months.
(iii) Congenital or primary valvular etiology.
(iv) Intolerant of statins.
(v) Liver disease.
(vi) Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception.
(vii) Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol.
(viii) Presence of any non-cardiac disease (e.g. cancer) that is likely to significantly shorten life expectancy.
(ix) Kidney abnormalities.

(9) GISSI-P trial was an open trial on secondary coronary heart disease prevention: 4,271 recent acute heart attack patients with total blood cholesterol more than 200 mg/dl (5.1 mmol/L) were randomised to pravastatin 20 mg daily or no treatment.

(10) Exclusion criteria for the LIPID trial:
(i) Clinically significant medical or surgical event within three months before study entry.
(ii) Heart failure.
(iii) Kidney or liver disease.

(11) CORONA exclusion criteria.
(i) Prior statin-induced myopathy or hypersensitivity.
(ii) Decompensated chronic heart failure or need for inotropic support.
(iii) Heart attack within past 6 months.
(iv) Unstable angina or stroke within past 3 months.
(v) Coronary artery bypass graft (or similar), pacemaker within past 3 months or plan to implant.
(vi) Prior heart transplant.
(vii) Significant uncorrected primary valvular heart disease.
(viii) Malfunctioning prosthetic valve.
(ix) Hypertrophic cardiomyopathy.
(x) Acute endomyocarditis/myocarditis.
(xi) Pericardial disease.
(xii) Systemic disease (eg, amyloidosis).
(xiii) Liver disease.
(xiv) Chronic muscle disease.
(xv) Prior cyclosporine.
(xvi) Life-limiting condition (cancer etc).
(xvii) Suspected poor compliance to protocol.

This investigation of the exclusion criteria and run-in phases of statin trials reveals the reasons that the large significant percentage of people are excluded from entering the statin studies.
(a) Most trials weed out people who are intolerant of statins.
(b) Subjects with liver or kidney problems are normally excluded.
(c) Women of child bearing age are routinely not allowed.
(d) Patients are often barred who have had surgical procedures.
(e) Most studies don't allow patients with a wide range of heart conditions.
(f) People who use drugs or alcohol are not included in statin studies.
(g) Up to 80% of screened potential subjects are rejected from the trials.
(h) Patients with various concomitant illness are invariably excluded from the trials.
(i) Patients taking a wide range of pharmaceutical drugs are not allowed into the studies.
(j) Poor mental function patients are screened out.
(k) Many of the trials weed out potential subjects who they suspect will have poor compliance in taking the statin drugs.

 

A couple of the studies have a 'run-in' phase where potential subjects are weeded out through various criteria. These trials have amounted to about a 50 to 80% exclusion rate before the trial begins. Nearly all the trials have a whole plethora of exclusion criteria and although it is very difficult to quantify how many people have been excluded, it may be argued that the 50 to 80% exclusion rate may be broadly similar.

 

How can we answer the question "do people taking statins have a shorter life?" 

 

The above eleven statin trials included 92,135 subjects. If we take the lower exclusion rate of 50%, then potentially about another 46,000 statin intolerant or statin incompatible people could have been included in the trials.

 

This would dramatically reduce the already paltry "three or four days statins add to life".

 

How can an accurate revised death rate figure can be calculated? I don't know if it's possible. But with data from an extra 46,000 statin intolerant people to be crunched there would be an exponential rise in side effects with a concomitant rise in deaths.

 

So, even if the actual exclusion rate figure is less than the estimated 50% exclusion rate figure, I suspect that this closer analysis of clinical trials reveals that statins may actually shorten life in the real world.

 

In type 1 diabetics, statins significantly increase the risk of developing diabetes-related complications.

This study was published in Diabetes Research and Clinical Practice 31st October 2015

Study title and authors:
Statins are Independently Associated with Increased HbA1c in Type 1 Diabetes–The Thousand & 1 Study
Magnus Thorsten Jensen, Henrik Ullits Andersen, Peter Rossing, Jan Skov Jensen

This study can be accessed at: http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(15)00423-4/abstract

The term HbA1c refers to glycated haemoglobin. It develops when haemoglobin, a protein within red blood cells that carries oxygen throughout your body, joins with glucose in the blood, becoming 'glycated'.

By measuring glycated haemoglobin (HbA1c), clinicians are able to get an overall picture of what our average blood sugar levels have been over a period of weeks/months.

For people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications.

This study examined the association between statin use and HbA1c levels in type 1 diabetics without known heart disease. The study included 1,093 patients, average age 49.6 years, who had had type 1 diabetes for an average of 25.5 years.

The study found that statin use was independently and significantly associated with higher HbA1c levels.



Stains increase the risk of age-related macular degeneration by 19%

This study was published in Ophthalmology 2009 Dec;116(12):2381-5

Study title and authors:
Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial.

Maguire MG, Ying GS, McCannel CA, Liu C, Dai Y
Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-3309, USA. maguirem@mail.med.upenn.edu

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19850347

The aim of the study was to evaluate the impact of statin use on the incidence of advanced age-related macular degeneration among patients with large drusen. The study included 744 patients, aged 50 years or more, who were followed for at least five years. Eligibility criteria for the clinical trial required that the participants have more than ten large drusen and visual acuity no better than 20/40 in each eye.

(Drusen are yellow deposits under the retina. While drusen likely do not cause age-related macular degeneration, their presence increases a person’s risk of developing age-related macular degeneration. In the expression, 20/40 vision, the 20 is the distance in feet between the subject and the chart. The 40 means that the subject can read the chart (from 20 feet away) as well as a normal person could read the same chart from 40 feet away).

The study found that patients taking statins had a 19% increased risk of developing advanced age-related macular degeneration compared to patients not taking statins.