Lowering cholesterol far below the level now considered adequate appears to substantially reduce patients’ risk of death from heart attacks. These findings from the “Prove It” Study (Pravastatin generic or Atorvastatin Evaluation and Infection Therapy) may change the way heart disease is treated. The study compared high doses of a powerful statin, or cholesterol-lowering drug, medication atorvastatin calcium (Lipitor®, Pfizer), with a less potent statin, pravastatin sodium (Pravachol®, Bristol-Myers Squibb). The patients taking Lipitor® were much less likely to have heart attacks or to need bypass surgery or angioplasty.

National guidelines currently call for levels of low-density lipoprotein (LDL) cholesterol, which carries cholesterol to arteries, to be below 100 mg/dl in high-risk patients.

In an earlier study, Drug Lipitor halted plaque growth and Pravachol® slowed but did not stop it. The current study suggests that for patients with recent acute coronary syndrome, an intensive lipid-lowering statin regimen might provide greater protection against death or major cardiovascular events than a standard regimen and that patients would benefit from early reduction of LDL cholesterol to below present target levels.

When is the best time to take a statin? The findings from several studies have been conflicting, although most statin manufacturers say that nighttime is ideal because most cholesterol is synthesized when dietary intake is low.

Researchers from the University of Sunderland in Tyne, Great Britain, randomly assigned 60 patients to take canadian simvastatin (Zocor medication, Merck) in the morning or evening for eight weeks. Patients who switched from evening to morning had statistically significantly higher total cholesterol and low-density lipoprotein-cholesterol (LDL, or “bad,” cholesterol) levels. From the baseline evaluation to week eight, total cholesterol values rose by an average of 0.38 mmol/liter and LDL-cholesterol levels rose by an average of 0.25 mmol/liter.

In a study of drug atorvastatin (Generic Lipitor®, Pfizer), no significant difference in cholesterol concentrations was observed between evening and morning, but the researchers note that this drug’s longer elimination half-life might be the explanation.

To combat the growing problem of counterfeit drugs, the government is searching for ways to tighten the security of medications and to make them more tamper-proof as they travel from factories to drugstores.

The FDA is considering asking manufacturers to ship tablets in smaller quantities (e.g., 30 pills in a blister pack instead of hundreds per shipment); smaller distributors would then rebottle them. Smaller sizes can make it more difficult for counterfeiters to sneak in fakes, although this step might put an end to companies that repackage or rebottle large shipments into the smaller bottles that patients receive.

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A new trial of simvastatin (Tablet Zocor, Merck) has raised a caution flag for patients taking high doses of statins. In a large study, simvastatin failed to show a benefit for very high-risk heart patients; however, it did increase the chances of rhabdomyolysis, a rare but dangerous side effect.

The study is likely to steer some doctors to try other drugs. In particular, atorvastatin (generic Lipitor, Pfizer) might benefit. However, this new trial did not reveal any problems with the safety or effectiveness of simvastatin for most patients, and it did not evaluate the most common use of simvastatin in patients with elevated risk of heart attacks or other cardiovascular problems who take 20 to 40 mg/day.

The trial, which included 4,500 patients, tested an aggressive cholesterol-lowering strategy compared with a moderate approach for patients with severe unstable chest pain. The aggressive treatment was 40 mg of simvastatin for one month, followed by 80 mg for the next 23 months. The moderate approach was four months of a placebo, followed by 20 mg of simvastatin.

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The FDA has approved Vytorin™, a combination tablet of generic ezetimibe (Zetia tablet, Schering-Plough), and drug simvastatin (Zocor medication, Merck). The medication combines a cholesterol blocker with a popular statin. It inhibits the production of cholesterol in the liver and blocks the absorption of cholesterol in the intestine, including cholesterol from food.

In a 12-week study, the drug reduced low-density lipoprotein cholesterol by 52% at the recommended starting dose (10/20 mg) and by 60% at the maximum dose (10/80 mg).

The new goals are expected to lead doctors to increase the use of drugs to reduce cholesterol levels when diet and exercise do not achieve the lower num­bers. At least 36 million patients are candidates for statins.

Only 50% of patients are still taking cholesterol drugs a year after beginning the regimen, doctors say. A combination tablet might make it easier for patients to remember to take their medications.

A single product would also carry one co-payment and could be less expensive, but whether Vytorin™ will be economical will depend on its price.

For more information about Vytorin™, see the Pharmaceutical-Approval Update on page 507 of this issue of P&T.

Pfizer Inc. has announced the FDA’s newest indication for atorvastatin calcium (Lipitor drug): to reduce the risk of stroke and heart attack in people with type-2 diabetes and to reduce the risk of stroke in people without diabetes but with other risk factors.

The FDA’s decision was based on the findings of the Collaborative Atorvastatin Diabetes Study (CARDS). This landmark trial involved more than 2,800 patients with type-2 diabetes, near-normal cholesterol levels, and at least one other risk factor (e.g., high blood pressure or smoking). The results showed patients taking generic atorvastatin experienced nearly 50% fewer strokes than those taking placebo. The trial was stopped two years early because of the strong benefits shown.

This additional indication also reflects findings from The Anglo-Scandinavian Cardiac Outcomes Trial: Lipid-Lowering Arm (ASCOT-LLA). In this trial, atorvastatin also reduced the relative risk of stroke by 26% compared with placebo.

According to the American Diabetes Association’s recommended treatment guidelines, adults with type-2 diabetes should be considered for statin therapy regardless of their low-density lipo-protein-cholesterol levels.

Traditional thinking has viewed atherosclerosis as “inexorably progressive,” say researchers who offer a more optimistic outlook: that aggressive treatment can actually reverse the atherosclerotic disease process.

They conducted a multinational study of very high-intensity rosuvastatin calcium (Crestor canadian, AstraZeneca) at a dose of 40 mg/day in 349 patients at 53 community and tertiary-care centers.

The treatment halved low-density lipo-protein (LDL)-cholesterol levels, from a mean of 130.4 to 60.8 mg/dl. Mean high-density lipoprotein (HDL) cholesterol increased 14.7%, from 43.1 mg/dl at the baseline evaluation to 49 mg/dl. The total atheroma volume declined by a median of 6.8%. The average change in the percentage of atheroma volume in the most diseased subsegment was -6.1 mm³.

Generic Rosuvastatin 40 mg/day was well tolerated, with no cases of rhabdomyolysis.