Study stopped early because statins increased the risk of acute kidney injury in patients with kidney disease

This study was published in the Journal of the American Medical Association 2016 Mar 1;315(9):877-88

 

Study title and authors:

High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Billings FT 4th, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ.

Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26906014

This study investigated the relationship between short-term high-dose perioperative atorvastatin and acute kidney injury following cardiac surgery. The study included 615 patients (199 statin-naïve and 416 statin-using) and 308 of these were randomized to atorvastatin and 307 to placebo. The average patient age was 67 years.
(i) Patients naive to statin treatment were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery or matching placebo.
(ii) Patients already taking a statin prior to study enrolment continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after or matching placebo, and resumed taking the previously prescribed statin on postoperative day 2.

The study found:
(a) After an interim review, the data and safety monitoring board recommended stopping the group naive to statin treatment due to a 235% increased risk of acute kidney injury among these participants with chronic kidney disease receiving atorvastatin.
(b) After a further review, the data and safety monitoring board later recommended stopping for futility, as the data revealed statins were increasing the risk of acute kidney injury by 6% overall and by 61% in statin naïve patients.
(c) Those who took statins had a 25% increased risk of the more serious stage 2 or stage 3 acute kidney injury compared to those who did not take statins.

The study also revealed:
(d) Those given the statins had a 20% increased risk of muscle pain compared to those taking placebo.
(e) Those given the statins had a 44% increased risk of stroke compared to those taking placebo.
(f) Those given the statins had a 11% increased risk of atrial fibrillation compared to those taking placebo.
(g) Those given the statins had a 202% increased risk of in hospital death compared to those taking placebo.

Links to other studies:
Statins increase the risk of diabetes in kidney transplant patients
Statin use is associated with a 30-36% increased incidence of acute and chronic kidney disease
Statin use associated with a 59% increased risk of kidney failure

Statins associated with a 54% increased risk of brain haemorrhage. Higher cholestreol levels associated with reduced risk

This study was published in the Journal of Neurology Neurosurgery and Psychiatry 2016 Mar 21. pii: jnnp-2015-312736

Study title and authors:
Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

Pezzini A, Grassi M, Iacoviello L, Zedde M, Marcheselli S, Silvestrelli G, DeLodovici ML
Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/27003275

This study investigated the effects between cholesterol levels and statins on the risk of intracerebral haemorrhage (where blood suddenly bursts into brain tissue, causing damage to the brain). The study included 3,492 patients with intracerebral haemorrhage, (average age 73 years), who were compared with 3,492 control subjects.

The study found:
(a) Each .26 mmol/l (10 mg/dL) increase in cholesterol levels was associated with a 13% decreased risk of  intracerebral haemorrhage.
(b) Statin users had a 54% increased risk of intracerebral haemorrhage compared to nonusers.

Links to other studies:
Patients taking statins after a stroke have a 68% increased risk of suffering another stroke
Statins increase the incidence of liver damage
Statins associated with increased bleeding in the brain in patients with intracerebral hemorrhage

Stroke victims taking statins have increased risk of death and a 140% increased risk of infection

This study was published in the European Journal of Neurology 2008 Jan;15(1):82-90

Study title and authors:
Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial.

Montaner J, Chacón P, Krupinski J, Rubio F, Millán M, Molina CA, Hereu P, Quintana M, Alvarez-Sabín J.
Neurovascular Research Laboratory, Neurovascular Unit, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 31862jmv@comb.es

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18070096

This study was a double-blind, randomised, multicentre clinical trial to study the effects of simvastatin in patients the first 90 days after a cortical stroke. The study included 60 patients with cortical strokes (a cortical stroke occurs when the blood supply to the outside, or cortex, of the brain is reduced or blocked, which results in brain damage) who were given either simvastatin or placebo at three to12 hours from symptom onset.

The study found:
(a) More patients taking simvastatin died compared to patients taking placebo.
(b) Patients taking simvastatin had a 140% increased risk of infection compared to patients taking placebo.

Links to other studies:
Patients taking statins after a stroke have a 68% increased risk of suffering another stroke
Statins increase the incidence of liver damage
Statins associated with increased bleeding in the brain in patients with intracerebral haemorrhage

Stroke patients with low cholesterol have an 87% increased risk of death

This study was published in the Journal of Stroke and Cerebrovascular Diseases 2013 Oct 5. pii: S1052-3057(13)00338-8

Study title and authors:
High Cholesterol Levels Are Associated with Improved Long-term Survival after Acute Ischemic Stroke.

Markaki I, Nilsson U, Kostulas K, Sjöstrand C.
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: ioanna.markaki@ki.se.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24103674

The aim of this study was to investigate the effect of cholesterol levels on death rates in patients that had suffered an ischemic stroke. (Ischemic stroke occurs when an artery to the brain is blocked). The study lasted for seven years and included 190 patients. Patients were classified as having high cholesterol, above 4.6 mmol/L (178 mg/dL), or low cholesterol, below 4.6 mmol/L (178 mg/dL).

The study found that ischemic stroke patients with low cholesterol had an 87% increased risk of death compared to ischemic stroke patients with high cholesterol.  

Statin use associated with increased risk of brain hemorrhage after stroke treatment

This study was published in Stroke 2009 May;40(5):1729-37

 

Study title and authors:

Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke.

Meier N, Nedeltchev K, Brekenfeld C, Galimanis A, Fischer U, Findling O, Remonda L, Schroth G, Mattle HP, Arnold M.

Department of Neurology, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19265056

Ischemic stroke occurs when an artery to the brain is blocked. Intra-arterial thrombolysis is a medical intervention that breaks down the blockages by pharmacological means. A complication of intra-arterial thrombolysis is intracranial (brain) hemorrhage.

The study evaluated the influence of statin pretreatment and cholesterol levels on the incidence of intracranial hemorrhage in 311 patients with acute ischemic stroke receiving intra-arterial thrombolysis treatment.

The study found:
(a) The cholesterol levels of patients who had an intracranial hemorrhage were 2.5% lower than patients who did not have an intracranial hemorrhage.
(b) Statin uses had a 210% increased risk of an intracranial hemorrhage compared to nonusers.
(c) Three months after their stroke, statin users had a 59% increased risk of death compared to nonusers.

The study shows that prior statin use is associated with a higher frequency of intracranial hemorrhage after intra-arterial thrombolysis treatment for ischemic stroke.

Statins associated with increased bleeding in the brain in patients with intracerebral hemorrhage

This study was published in Stroke 2012 Jul 24

Study title and authors:

Statin Use and Microbleeds in Patients With Spontaneous Intracerebral Hemorrhage.

Haussen DC, Henninger N, Kumar S, Selim M.

From the Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22829545

Microbleeds (or microhaemorrhages) are pinpoint drops of blood that leak from blood vessels in the brain and increase may increase the risk of stroke and cognitive dysfunction.

The cortico-subcortical region of the brain is the outer layers and the area beneath the outer layers.

The study investigated the effects that statin use had on microbleeds in patients with intracerebral hemorrhage. The study included 163 patients with intracerebral hemorrhage.

The study found:
(a) Statin users had significantly lower cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to non users.
(b) Statins users had a 172% increase in microbleeds compared to non users.
(c) Statins users had a 315% increase in cortico-subcortical microbleeds compared to non users.

The study shows that statin use is associated with increased bleeding in the brain in patients with intracerebral hemorrhage.

Statins double the risk of stroke

This study was published in the New England Journal of Medicine 2005 Jul 21;353(3):238-48

Study title and authors:

Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.

Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, Ritz E; German Diabetes and Dialysis Study Investigators.

Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany. wanner_c@medizin.uni-wuerzburg.de

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16034009?dopt=Abstract

This study investigated the effects of statin (atorvastatin) treatment in diabetic patients receiving hemodialysis. The study included 1,255 subjects with type 2 diabetes who were receiving hemodialysis who were assigned to receive either 20 mg of atorvastatin per day or matching placebo.

The study found:

• Those receiving atorvastatin had twice the risk of a fatal stroke.
• Death rates were similar in both groups.

This study found that atorvastatin increased stroke risk and had no effect on total death rates.  

Statins increase the risk of hemorrhagic stroke by 73%

This post includes a synopsis of a paper published in Stroke 2008;39:497 and a recipe for balsamic glazed pork steak with stir fried broccoli.

Study title and authors:
Statin Treatment and the Occurrence of Hemorrhagic Stroke in Patients With a History of Cerebrovascular Disease

Mervyn D.I. Vergouwen, MD; Rob J. de Haan, PhD; Marinus Vermeulen, MD, PhD; Yvo B.W.E.M. Roos, MD, PhD

Books:

From the Departments of Neurology (M.D.I.V., M.V., Y.B.W.E.M.R.) and Clinical Epidemiology and Biostatistics (R.J.d.H.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

This paper can be accessd at: http://stroke.ahajournals.org/cgi/content/abstract/39/2/497

The purpose of this review was therefore to investigate the effect of statin treatment on the occurrence of ischemic and hemorrhagic strokes in patients with a history of cerebrovascular disease.

The study found that:
(a) Statins decreased the risk of  ischemic stroke by 20%
(b) Statins increased the risk of hemorrhagic stroke by 73%

More information on this subject: Books : Scientific Studies : Other Websites : Videos : Food Mall

Recipe of the day

Balsamic Glazed Pork Steak with Stir Fried Broccoli

Ingredient list:


2 bone-in pork steaks

3 stalks of broccoli
Coconut oil
Balsamic vinegar
Garlic powder
Jamaican Allspice
Salt

Directions:
Pre-heat non-stick grill-pan or skillet over medium heat. Season both sides of pork steak with salt, garlic powder, and Jamaican Allspice. Lay pork steak in the hot grill-pan and let sear undisturbed for 6 minutes. Turn with tongs to let the second side sear for 6 minutes. Splash balsamic vinegar generously across the top of the meat. After the second side has seared, turn again and coat the other side with balsamic vinegar. Turn again and let the freshly coated side sear a few more seconds. Meanwhile, cut florets from broccoli stalks and divide into bite-sized pieces. Melt two tablespoons of coconut oil over medium heat in a wok. Add broccoli and stir until broccoli is coated with coconut oil. Add a little water if the wok becomes too dry before the broccoli is sufficiently tender. When done, transfer pork steaks to a plates. Fill the rest of the plate with broccoli. Enjoy!

Statins increase the incidence of liver damage

This post includes a synopsis of a study published in the New England Journal of Medicine 2006; 355:549-559 August 10, 2006

Study title and authors:
High-Dose Atorvastatin after Stroke or Transient Ischemic Attack

Karam JG et al The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators
This study can be accessed at: http://www.nejm.org/doi/full/10.1056/NEJMoa061894

The study divided up 4731 patients who had had a stroke into 2 groups who had treatment of either (i) 80 mg of a statin drug per day or (ii) placebo.

Elevated liver enzymes may indicate the liver is damaged.

The study found:
(a) The statin group had a 66% higher incidence of  hemorrhagic strokes.
(b) The statin group had a 2.31% more deaths.
(c) Elevated liver enzyme values were more common in patients taking statins.



Patients taking statins after a stroke have a 68% increased risk of suffering another stroke

This post includes a summary of a paper published in Neurology June 10, 2008 vol. 70 no. 24 Part 2 2364-2370

Study title and authors:
Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study
L. B. Goldstein, MD, P. Amarenco, MD, M. Szarek, MS, A. Callahan III, MD, M. Hennerici, MD, PhD, H. Sillesen, MD, DMSc, J. A. Zivin, MD, PhD, K.M.A. Welch, MB, ChB and On behalf of the SPARCL Investigators*

This paper can be accessed at: http://www.neurology.org/content/70/24_Part_2/2364.abstract

This paper analysed the association between statins and hemorrhagic stroke in patients who had suffered a recent stroke. The study was a double-blind, randomized, placebo-controlled trial and included 4,731 patients, aged 18 years and over, who were followed for 4.9 years. The patients received either:
(i) Atorvastatin 80 mg per day.
(ii) Placebo.

The study found:
(a) Patients who received the statin had a 68% increased risk of fatal and non-fatal hemorrhagic stroke compared to those who received placebo.
(b) Patients who received the statin had a 140% increased risk of non-fatal hemorrhagic stroke compared to those who received placebo.

Patients taking statins after a stroke have an increased risk of suffering another stroke.