Statins associated with a 75% increased risk of death in patients with lung disease

This study was published in the American Thoracic Society Journal 2010.181.1_MeetingAbstracts.A170110.1164

Study title and authors:
Effect Of Statin Therapy On Outcomes In Patients With Acute Lung Injury And Acute Respiratory Distress Syndrome.
Seth R. Bauer, PharmD, Simon W. Lam, PharmD, Anita J. Reddy, MD

This study can be accessed at: http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A1701

Acute lung injury/acute respiratory distress syndrome is a life-threatening medical condition where the lungs can't provide enough oxygen for the rest of the body.

This study investigated the effects of statins on patients diagnosed with acute lung injury/acute respiratory distress syndrome who received treatment in an intensive care unit setting. The study included 187 patients who were divided into three groups:
(i) Patients who received statins before and continued after acute lung injury/acute respiratory distress syndrome diagnosis.
(ii) Patients who received statins before but not after acute lung injury/acute respiratory distress syndrome diagnosis.
(iii) Patients who never had statins.

The study found:
(a) Overall, patients who received statins had a 75% increased risk of death compared to patients who never had statins.
(b) Patients who received statins before and continued after acute lung injury/acute respiratory distress syndrome diagnosis had a 114% increased risk of death compared to patients who never had statins.
(c) Patients who received statins before but not after acute lung injury/acute respiratory distress syndrome diagnosis had a 41% increased risk of death compared to patients who never had statins.

Links to other studies:
Link between statin use and interstitial lung disease
63.5% of patients report experiencing side-effects due to statins
Doctor says statin drug hypersensitivity reactions are potentially life-threatening

Acute exacerbations and infections increase in patients with chronic obstructive pulmonary disease who take aspirin and statins

This study was published in the International Journal of Medical Sciences 2015 Mar 2;12(3):280-7

 

Study title and author:

No Significant Detectable Anti-infection Effects of Aspirin and Statins in Chronic Obstructive Pulmonary Disease.

Yayan J.

Department of Internal Medicine, Division of Pulmonary, Allergy and Sleep Medicine, Saarland University Medical Center, Homburg/Saar, Germany.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25798054

Chronic obstructive pulmonary disease is the name for a collection of lung diseases including chronic bronchitis, emphysema and chronic obstructive airways disease.

This study examined  the effect of using aspirin and statins in the exacerbation and infection in patients with chronic obstructive pulmonary disease. The study included 300 patients, average age 69 years, with chronic obstructive pulmonary disease.

The study found:
(a) Patients taking aspirin and statins were 40% more likely to develop an infection than not develop an infection.
(b) Patients taking statins alone were 230% more likely to develop an infection than not develop an infection.
(c) Patients not taking either aspirin or statins were 40% LESS likely to develop an infection than develop an infection.
(d) Patients taking aspirin and statins had a 16% increased risk of acute exacerbation of chronic obstructive pulmonary disease compared to patients not taking either aspirin or statins.
(e) Patients taking statins alone had a 56% increased risk of acute exacerbation of chronic obstructive pulmonary disease compared to patients not taking either aspirin or statins.

Yayan concluded: "In this study, the number of acute exacerbations and infections increased in patients with chronic obstructive pulmonary disease who took aspirin and statins compared with those who took neither aspirin nor statins".

Statin use is associated with a 60% increased risk of interstitial lung abnormalities in smokers

This study was published in the American Journal of Respiratory and Critical Care Medicine 2012 Mar 1;185(5):547-56

 

Study title and authors:

Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation.

Xu JF, Washko GR, Nakahira K, Hatabu H, Patel AS, Fernandez IE, Nishino M, Okajima Y, Hunninghake GM

Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22246178

The objective of the study was to evaluate the association between statin use and interstitial lung disease in smokers. The study included 2,115 subjects who were smokers and had had a CT scan. (A CT (computerised tomography) scan uses X-rays and a computer to create detailed images of the inside of the body).

The study found, that in people that smoke, statin users have a 60% increased risk of interstitial lung abnormalities compared to those who don't take statins.

Xu concludes: "Our findings demonstrate that statin use is associated with interstitial lung abnormalities among current and former smokers". 

Doctor says statin drug hypersensitivity reactions are potentially life-threatening

This paper was published in Chest 1999 Mar;115(3):886-9

Study title and authors:
Polymyalgia, hypersensitivity pneumonitis and other reactions in patients receiving HMG-CoA reductase inhibitors: a report of ten cases.

Liebhaber MI, Wright RS, Gelberg HJ, Dyer Z, Kupperman JL.
Department of Medicine and Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA. mil1258@pol.net

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10084510

 
This paper, headed by Dr Myron Liebhaber from the University of California Los Angeles School of Medicine, describes ten patients who developed hypersensitivity-type reactions after taking statin medications. (A hypersensitivity reaction is an exaggerated inflammatory response by the immune system to a drug or other foreign substance).
 
Patient 1
(i) Nine months after starting lovastatin, 20 mg daily, a 54 year old man developed urticaria over his entire body and angioedema of his upper lip. (Urticaria also known as hives, is a kind of skin rash with pale red, raised, itchy bumps. Angioedema is swelling under the skin).
(ii) Tests revealed an autoimmune disorder (where the body attacks its own tissues).
(iii) Lovastatin was discontinued, and his symptoms gradually resolved over seven days. 
 
Patient 2
(i) A 69-year-old woman was referred for medical attention for an evaluation of a cough.
(ii) She had been taking pravastatin, 20 mg to 40 mg daily, for 6 years.
(iii) She was given medication and her condition improved although tests revealed impaired lung function.
(iv) Over the next six weeks her symptoms became much worse and she was given medication.
(v) Despite the treatment her cough continued.
(vi) A scan found inflammation in the lungs.
(vii) A lung biopsy led to a diagnosis of pravastatin induced hypersensitivity pneumonitis. (Hypersensitivity pneumonitis is a disease in which your lungs become inflamed when they are exposed to substances to which you are allergic).
(viii) The pravastatin was stopped, and her cough resolved two weeks later.
(ix) A follow-up scan seven weeks after the first one showed complete resolution of the inflammation in her lungs.

Patient 3
(i) Three years after starting pravastatin 20 mg daily, a 77 year old man developed gradually increasing inflammation, with symptoms of polymyalgia. (Polymyalgia is pain, stiffness and tenderness in many muscles).
(ii) In addition, three years after starting pravastatin, the patient had retinal vein thrombosis. (Retinal vein thrombosis is when one of the tiny retinal veins becomes blocked by a blood clot).
(iii) The patient then developed a sudden worsening of his heart function.
(iv) After discontinuing the pravastatin his heart function normalized, and resolution of the polymyalgia syndrome occurred over one month.

Patient 4
(i) A 66-year-old man started taking lovastatin, 20 mg daily.
(ii) Four years later, the patient complained of fatigability, drowsiness, shortness of breath and joint pain.
(iii) Tests revealed inflammation and an autoimmune disorder.
(iv) He stopped taking lovastatin.
(v) His symptoms gradually resolved over two months.

Patient 5
(i) A 76-year-old woman  was started on lovastatin, 20 mg daily.
(ii) One year later she began to complain of muscle aches.
(iii) Two years later, she developed shortness of breath, joint pain and psoriasis. (Psoriasis is inflammation of the skin and develops as patches of red, scaly skin).
(iv) She then had a small heart attack and a failed artery graft.
(v) Lovastatin was discontinued, and she had a gradual improvement of her shortness of breath, joint pain, muscle pain and back pain over a two month period.

Patient 6
(i) An 80-year-old woman had been taking simvastatin, 10 mg daily, for 3 years.
(ii) She began having shortness of breath on exertion.
(iii) Investigations revealed she had inflammation.
(iv) Simvastatin was discontinued.
(v) Her shortness of breath improved and inflammation decreased over the next three weeks.

Patient 7
(i) A 49-year-old man had been taking pravastatin, 40 mg daily, for four years.
(ii) During this period, he had generalised itching and urticaria, along with swelling of his fingers and feet.
(iii) Test revealed an autoimmune disorder.
(iv) Pravastatin was discontinued, and the itching and swelling gradually resolved over the subsequent month.

Patient 8
(i) A 77-year-old woman was treated with pravastatin, 10 mg daily, for 3 years.
(ii) During this period, she had generalised itching with urticaria.
(iii) Investigations revealed she had inflammation and an autoimmune disorder.
(iv) Her symptoms cleared one month after discontinuing the pravastatin.

Patient 9
(i) A 53 year old man started to take pravastatin 40 mg daily.
(ii) Within six months he developed angioedema (swelling) of the eyelids and a sensation of his airway closing. 
(iii) He discontinued pravastatin.
(iv) His symptoms gradually resolved 30 days later.

Patient 10
(i) A 73-year-old man developed intense itching and urticaria after taking pravastatin 20 mg daily for three years. 
(ii) Tests revealed she had an autoimmune disorder.
(iii) He discontinued pravastatin and 12 days later his symptoms resolved.

Dr Liebhaber concluded: "We feel it is important for clinicians to recognize early symptoms of statin drug hypersensitivity because they are potentially life-threatening".

Link between statin use and interstitial lung disease

This paper was published in the Medical Journal of Australia 2007 Jan 15;186(2):91-4

Study title and authors:
Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease.

Walker T, McCaffery J, Steinfort C.
Geelong Hospital, Geelong, Victoria, Australia. timw@barwonhealth.org.au

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17223772

Dr Tim Walker from Geelong Hospital Australia describes seven patients who developed interstitial lung disease while on statin treatment. Interstitial lung disease refers to a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). (Interstitial pneumonitis is a type of interstitial lung disease).

Patient 1
(i) A 78 year old woman was admitted to hospital with shortness of breath and a dry cough.
(ii) She had been taking atorvastatin 10 mg per day for one year.
(iii) Investigations revealed extensive fibrous connective tissue (fibrosis) in the lungs.
(iv) Atorvastatin was withdrawn.
(v) Her lung function got slowly worse, and she still had shortness of breath at a three year check up.

Patient 2
(i) A 78 year old man sought medical attention at hospital after suffering from shortness of breath for three weeks.
(ii) He had been taking pravastatin 40 mg daily for ten years.
(iii) Investigations revealed extensive emphysema, fibrosis and impaired lung function.
(iv) He initially continued statin treatment and experienced respiratory failure necessitating home oxygen therapy before stopping statins.
(v) He died 18 months later of respiratory failure.

Patient 3
(i) A 74 year old woman was admitted to hospital with a cough and fever of three days duration, (consistent with pneumonia), and a background of worsening shortness of breath.
(ii) She had been taking simvastatin 10 mg daily for two years, then 20 mg daily for one year.
(iii) Investigations found extensive infiltration (fluid, fibrosis) of the lungs and a biopsy led to a diagnosis of interstitial pneumonitis.
(iv) Simvastatin was withdrawn.
(v) There was a gradual reduction in infiltrate, and her lung function was stable at a nine-month follow up.

Patient 4
(i) An 83 year old man arrived at hospital with shortness of breath which had worsened over a six month period.
(ii) He had been taking pravastatin for one year.
(iii) Investigations revealed he had fibrosis.
(iv) He stopped taking pravastatin.
(v) Despite withdrawl of pravastatin his condition slowly worsened.

Patient 5
(i) A 67 year old woman sought medical help after suffering with shortness of breath for nine months and a dry cough for six months.
(ii) She had been taking simvastatin for five years.
(iii) Investigations found patchy infiltration of her lungs and she had a TLCO of 22%. (TLCO is Transfer factor of the lung for carbon monoxide and is the extent to which oxygen passes from the air sacs of the lungs into the blood. A low TLCO indicates fibrosis and restrictive lung disease).
(iv) She stopped taking simvastatin.
(v) She had a marked improvement: TLCO increased to 51% after one month, and improved further to 65% after one year.

Patient 6
(i) A 68 year old man was admitted to hospital with worsening shortness of breath and hypoxia. (Hypoxia is where there is not enough oxygen getting to the tissues of the body).
(ii) He had been taking simvastatin for two years.
(iii) Investigations revealed he had inflammation and fibrosis in the lungs.
(iv) He continued to take simvastatin.
(v) He died nine months later from heart disease exacerbated by interstitial lung disease.

Patient 7
(i) A 64 year old man sought medical attention for worsening shortness of breath and a dry cough.
(ii) He had been taking atorvastatin 20 mg daily for three years, then 40 mg daily for two years.
(iii) Investigations found the patient had fibrosis. he had a TLCO of 44%.
(iv) Atorvastatin was withdrawn.
(v) He had an improvement in his condition. His TLCO increased to 52% after two months.

Dr Walker also reviewed some other adverse side effects that statins may cause.

He found:
(a) The most commonly reported adverse effects include gastrointestinal upset, headache, rash and a dose-dependent elevation in levels of liver transaminases (enzymes).
(b) The most potentially serious, adverse effects include myopathy (muscle disease) and polyneuropathy (life threatening neurological disorder that occurs when many nerves throughout the body malfunction simultaneously).
(c) Statins have been associated with lung diseases, lupus-like syndromes and muscle and skin inflammation diseases.
(d) Many patients take statin therapy for many months or years before these symptoms develop.
(e) Their clinical features vary in severity from mild dry cough and rash through to severe and progressive respiratory failure.

Dr Walker concluded: "We hope that our description of our patients and review of the possible role of statins in interstitial lung disease will raise awareness of the potential association between statin therapy and this uncommon and often fatal condition".

Statins may induce interstitial lung disease

This paper was published in Chest 2008 Oct;134(4):824-30

Study title and authors:
Statins and interstitial lung disease: a systematic review of the literature and of food and drug administration adverse event reports.

Fernández AB, Karas RH, Alsheikh-Ali AA, Thompson PD.
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18689579

This study reviewed the scientific literature to examine the relationship between statins and interstitial lung disease. (Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to get enough oxygen. The scarring is called pulmonary fibrosis).

After reviewing evidence from the previous 20 years the researchers concluded: "Statin-induced interstitial lung disease is a possible newly recognized side effect of statin therapy".

Statins worsen lung function in patients with lymphangioleiomyomatosis

This study was published in the European Respiratory Journal 2009 Aug;34(2):513-4

Study title and authors:

Statins in lymphangioleiomyomatosis: a word of caution.

El-Chemaly S, Taveira-DaSilva A, Stylianou MP, Moss J.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19648526

Lymphangioleiomyomatosis is a rare progressive cystic lung disease.

FEV1% (forced expiratory volume) is the volume of air exhaled during the first second. So the lower the measurement - the lower the lung function. FEV1% predicted is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex and body composition.

DL,CO% (diffusing capacity of the lung for carbon monoxide) is the extent to which oxygen passes from the air sacs of the lungs into the blood. The lower the measurement - the less oxygen there is - the lower the lung function. DL,CO% predicted is defined as DL,CO% of the patient divided by the average DL,CO% in the population for any person of similar age, sex and body composition.

This three year study evaluated the effects of statins on lung function in 335 patients with lymphangioleiomyomatosis.

The study found:

(a) Those taking statins had a 1.9% yearly decline in FEV1% predicted levels compared to those not taking statins.

(b) Those taking statins had a 3.7% yearly decline in DL,CO% predicted levels compared to those not taking statins.

This study shows that statins worsen lung function in patients with lymphangioleiomyomatosis.

Statins induce pneumonia

This post includes a summary on a paper published in the European Respiratory Journal 2002; 19:577-580

Study title and authors:

Books:

Statin-induced fibrotic nonspecific interstitial pneumonia

S. Lantuejoul1, E. Brambilla1, C. Brambilla2 and G. Devouassoux2

Depts of 1 Cellular Pathology and 2 Respiratory Medicine, Centre Hospitalier Universitaire de Grenoble, Université J.

This paper can be accessed at: http://www.erj.ersjournals.com/cgi/content/abstract/19/3/577

Nonspecific interstitial pneumonia is a disorder that affects the tissue that surrounds and separates the tiny air sacs of the lungs.

This paper describes a case of statin-induced lung injury, with a histological pattern of nonspecific interstitial pneumonia.

(i) A 51‐year-old male was admitted to hospital with fever, polymyalgia, cough and progressive dyspnoea for one month. He was been treated with simvastatin (Zocor) (5 mg·day) for six years.
(ii) Drug-induced pneumonitis (inflammation of the lungs) was highly suspected, so the simvastatin was discontinued and a corticosteroid therapy was added.
(iii) One month later the patients symptoms had not improved and investigations led to a diagnosis of fibrotic nonspecific interstitial pneumonia.
(iv) Six months later, a progressive response to corticosteroid therapy was observed with improvement of symptoms.
(v) One-month later, pravastatin (pravachol) was inadvertently introduced, and he rapidly deteriorated. He had shortness of breath, muscle pain and tests revealed abnormal substances in his lungs.
(vi) Statins were stopped, which led to progressive improvement.

This case highlights that pneumonia may be induced by statins

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