Atorvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body. Buildup of cholesterol and fats along the walls of the blood vessels (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. Lowering blood levels of cholesterol and fats may help to prevent heart disease, angina (chest pain), strokes, and heart attacks.  Atorvastatin is used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and certain fatty substances in the blood. Atorvastatin reduces cholesterol levels, but there is no evidence that the use of atorvastatin increases longevity. Caduet is a prescription drug that combines two medicines, amlodipine besylate and atorvastatin calcium. Lipitor is the brand name for atorvastatin.
   See natural ways to lower cholesterol levels.

Atorvastatin and Stroke - Possible increase in mortality with atorvastatin use

Atorvastatin is being promoted for use after stroke, but my interpretation of the study listed below (which was highly publicized as atorvastatin reducing the risk of stroke) leads me to believe that those who use atorvastatin either don't live longer, or may actually die sooner. So, what's the point of wasting 150 dollars a month on atorvastatin and incurring the possible atorvastatin side effects such as liver damage, muscle tissue breakdown, and other health risks?
 

High-Dose Atorvastatin after Stroke or Transient Ischemic Attack
Volume 355:549-559 August 10, 2006 Number 6  The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators
Pierre Amarenco, M.D. (Denis Diderot University, Paris), Julien Bogousslavsky, M.D. (University of Lausanne, Lausanne, Switzerland), Alfred Callahan, III, M.D. (Neurologic Consultants, Nashville), Larry B. Goldstein, M.D. (Duke University Medical Center, Durham, N.C.), Michael Hennerici, M.D., Ph.D. (Universitat Heidelberg, Mannheim, Germany), Amy E. Rudolph, Ph.D. (Pfizer, New York), Henrik Sillesen, M.D., D.M.Sc. (University of Copenhagen, Copenhagen), Lisa Simunovic, M.S. (Pfizer, New York), Michael Szarek, M.S. (Pfizer, New York), K.M.A. Welch, M.B., Ch.B., (Rosalind Franklin University of Medicine and Science, North Chicago), and Justin A. Zivin, M.D., Ph.D. (University of California, San Diego) assume full responsibility for the overall content and integrity of the article. Editorial by Kent, D. M.
Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established. We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke. Results: The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 5 years, 265 patients (11 percent) receiving atorvastatin and 311 patients (13 percent) receiving placebo had a fatal or nonfatal stroke. The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent. The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group, as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin. Conclusions: In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke.

Comment by Lou Mancano, M.D.
I read your September Newsletter today regarding the atorvastatin and stroke study. You might comment in a future edition on the Number Needed to Treat (NNT) analysis. The NNT is the number of patients who need to be treated in order to prevent one additional bad outcome. It is the inverse of the Absolute Risk Reduction (ARR). How to Calculate NNTs.

NNT = 1/ARR
ARR = [CER - EER]
where
CER = control group event rate
EER = experimental group event rate

In the statin and stroke article, the CER was 13% and the EER was 11%. Therefore the ARR is 2%. One divided by 0.02 = 50. Therefore, one needs to treat 50 patients to avoid one stroke, meaning 49 out of 50 patients derive no benefit.

Atorvastatin side effects
Many people who take atorvastatin notice side effects such as muscle problems and liver problems. Atorvastatin side effects reported include muscle pain, tenderness, or weakness. Rarely, there can be flulike symptoms or yellowing of the skin or eyes, abdominal pain, unexplained fatigue, dark colored urine or pale colored stools. These may be early symptoms of muscle or liver problems and are considered a serious atorvastatin side effect.

Atorvastatin may cause drug-induced liver injury and such liver injury may be followed by prolonged cholestasis and interlobular bile duct injury.

Atorvastatin does not reduce cardiovascular risk in those with diabetes

Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN).
Diabetes Care. 2006 Jul;29(7):1478-85. Knopp RH, d'Emden M, Smilde JG, Pocock SJ.
Harborview Medical Center, 325 Ninth Ave., #359720, Seattle, WA
The purpose of this study was to evaluate the effect of 10 mg of atorvastatin versus placebo on cardiovascular disease prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets. Subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a 4-year, double-blind, parallel-group study. The composite primary end point comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and worsening or unstable angina requiring hospitalization. Composite end point reductions were not statistically significant. This result may relate to the overall study design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines. For these reasons, the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of therapy.

Increase in blood sugar and glycated hemoglobin
Atorvastatin Causes Insulin Resistance and Increases Ambient Glycemia in Hypercholesterolemic Patients
Journal of the American College of Cardiology, March 2010. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK;
We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients. Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction. A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in patients given daily atorvastatin 10, 20, 40, and 80 mg, during a 2-month treatment period. Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline or placebo. Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively). Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients.

Atorvastatin does not help Aortic Stenosis

The popular cholesterol-reducing drug atorvastatin made by Pfizer does not prevent obstruction of the heart valve that leads to the aorta, the body's largest artery, according to June 2005 findings published in The New England Journal of Medicine. In a study conducted to determine whether the cholesterol drug atorvastatin did more than just reduce cholesterol, doctors found that atorvastatin failed to prevent obstructions that can keep the heart from pumping blood adequately. The condition, known as calcified aortic stenosis, occurs when a key heart valve narrows or becomes blocked, preventing the heart from pumping blood properly and can manifest itself in spite of reductions of cholesterol levels.

Role of coenzyme q10
Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin.
J Clin Lipidol. 2008 Aug; Pacanowski MA, Frye RF, Enogieru O, Schofield RS, Zineh I. University of Florida College of Pharmacy, Department of Pharmacy Practice and Center for Pharmacogenomics; Gainesville, FL, USA.
Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10. We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes. Individuals without dyslipidemia or known cardiovascular disease received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10. Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment. After 16 weeks of atorvastatin, plasma CoQ10 decreased 45%. CoQ10 changes were correlated with LDL-C and apolipoprotein B changes, but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions. Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia.

Atorvastatin increases blood ratios of vitamin E/low-density lipoprotein cholesterol and coenzyme Q10/low-density lipoprotein cholesterol in hypercholesterolemic patients.
Nutr Res. 2010 Feb; Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
Statins are among the most widely used drugs in the management of hypercholesterolemia. In addition to inhibiting endogenous cholesterol synthesis, however, statins decrease coenzyme Q10 (CoQ10) synthesis. CoQ10 has been reported to have antioxidant properties, and administration of drugs that decrease CoQ10 synthesis might lead to increased oxidative stress in vivo. Our present study examined the hypothesis that atorvastatin increased oxidative stress in hypercholesterolemic patients due to its inhibition of CoQ10 synthesis. We investigated the effects of atorvastatin (10 mg/d) administration for 5 months on lowering hypercholesterolemia and blood antioxidant status. The study population included 19 hypercholesterolemic outpatients. Blood levels of lipid and antioxidant markers, consisting of vitamin C, vitamin E, CoQ10, and glutathione (GSH), and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined pre- and postadministration of atorvastatin. Atorvastatin administration resulted in a significant decrease in blood levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, vitamin E, and CoQ10; however, a significant increase in the ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol was noted. Atorvastatin had no significant effect on red blood cell (RBC) level of GSH and urinary 8-OHdG. The present study provides evidence that atorvastatin exerts a hypocholesterolemic effect, but on the basis of the urinary level of 8-OHdG and the blood ratios of vitamin E/LDL cholesterol and CoQ10/LDL cholesterol, has no oxidative stress-inducing effect.

Atorvastatin and Fish Oils

Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity.
Am J Clin Nutr. 2006 Jul;84(1):37-43.

Disturbed HDL metabolism in insulin-resistant, obese subjects may account for an increased risk of cardiovascular disease. Fish oils and atorvastatin increase plasma HDL cholesterol, but the underlying mechanisms responsible for this change are not fully understood. We studied the independent and combined effects of fish oils and atorvastatin on the metabolism of HDL apolipoprotein A-I (apo A-I) and HDL apo A-II in obese men. Conclusion: : Fish oils, but not atorvastatin, influence HDL metabolism chiefly by decreasing both the catabolism and production of HDL apo A-I and HDL apo A-II in insulin-resistant obese men. Addition of atorvastatin to treatment with fish oils had no additional effect on HDL kinetics compared with fish oils alone.