The Cholesterol Lowering Statin Drugs — Not All Have Proven Health Benefits

There are currently six cholesterol lowering statin drugs approved by the Food and Drug Administration (FDA) on the market in the United States. They are atorvastatin (LIPITOR), fluvastatin (LESCOL), lovastatin (MEVACOR), pravastatin (PRAVACHOL), rosuvastatin (CRESTOR), and simvastatin (ZOCOR).  

These drugs generate close to $20 billion in sales every year. Although they all lower cholesterol, not all of them can legally claim that they actually benefit patients by reducing the risk of a first or second heart attack or stroke. Simply lowering cholesterol is not enough. In fact, in the long history of cholesterol lowering drugs, stretching back to the early 1960s, there are a number of tragic episodes of injuries and deaths.

Early in 1962, the cholesterol lowering drug triparanol (MER/29) came off the market because it caused cataracts. When triparanol was first marketed, as Morton Mintz wrote,“It held a dazzling promise: without changes in diet, merely by swallowing a 35-cent anticholesterol capsule before breakfast ... [it] could reverse or inhibit atherosclerosis [clogging of the arteries] and its related diseases.” Another cholesterol lowering drug, clofibrate (ATROMID-S), approved by the FDA in 1967, was found in a clinical trial to statistically significantly increase deaths compared to patients receiving a placebo. The statin drug cerivastatin (BAYCOL) was withdrawn from the market in 2001 because it caused a large number of  potentially fatal muscular adverse reactions called rhabdomyolysis (see Worst Pills, Best Pills News October 2001). The uniquely dangerous statin rosuvastatin (CRESTOR) can now be added to this list of unacceptable cholesterol lowering drugs. The FDA approved rosuvastatin in 2003. We petitioned the FDA to have this drug removed from the market in March 2004 (see Worst Pills, Best Pills News October 2003).

This article compares the proven health benefits (or lack thereof) of the six statins now on the market. The criterion used for identifying a proven health benefit for a particular statin drug is whether the benefit — reducing the risk of a first or second heart attack or stroke — is included in the FDA approved professional product labeling for that statin. The professional product labeling, also known as the package insert, is the tightly folded piece of paper written in dense technical jargon that is delivered to the pharmacy with each container of medication. It is not routinely distributed to prescription drug consumers.

The standard for getting a claim approved by the FDA and into a drug’s professional labeling is much higher than the standard for getting a study published, even in the most prestigious medical journals. The published medical literature can be used by drug manufacturers as another form of promotion and not necessarily as a means of scientific communication. In some respects, there has been a blurring of the boundaries between science and advertising.    

Some of the statins are approved by the FDA for uses other than lowering cholesterol. One example is reducing the risk of a cardiac revascularization procedure. This is  a surgical procedure to restore blood supply to the heart, such as placing a heart stent. Some of the statins are also approved to manage angina or chest pain. Reducing the risk of a surgical procedure or chest pain is important but does not rise to the level of reducing the risk of a heart attack or stroke.

Each of the statin drugs is listed below in alphabetical order by generic name. The brand name is given in capital letters. There are brief comments on the particular statin and information taken directly from the FDA-approved professional product labeling about the drug’s effect on heart attack and stroke.

The table at the end of this article summarizes what is proven about the statins’ ability to reduce the risk of heart attack and stroke.

Atorvastatin (LIPITOR)

Atorvastatin is the largest-selling drug in the U.S. with 57 million prescriptions dispensed and over $5.5 billion in retail sales in 2003. Atorvastatin was approved by the FDA in December 1996, but remarkably, it was not until mid-2004 that the following health benefit claim could be made in the drug’s professional product labeling:

Prevention of Cardiovascular Disease

In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age 55 years, smoking, hypertension [high blood pressure], low HDL-C [good cholesterol], or a family history of early coronary heart disease, Lipitor is indicated to:

Reduce the risk of myocardial infarction [heart attack]

The professional product labeling for atorvastatin was last revised in July of 2004.

Fluvastatin (LESCOL, LESCOL XL)

Combined, LESCOL and LESCOL XL accounted for more than 4.8 million prescriptions dispensed and retail sales approaching $333 million in 2003. Fluvastatin was approved for marketing in December 1993.

At this time no claim can be made in fluvastatin’s professional product labeling that this statin can reduce the risk of a heart attack or stroke.

The professional product labeling for fluvastatin was last revised in May 2003.

Lovastatin (MEVACOR)

Lovastatin is now available as a generic. MEVACOR, the brand name product, was no longer among the top 200 selling drugs in the U.S. in 2003. The sales of the generic product topped $276 million, with almost 4 million prescriptions dispensed in 2003. Lovastatin was approved by the FDA in August 1987.

The following benefit claim is made in the professional product labeling for lovastatin:

Primary Prevention of Coronary Heart Disease

In individuals without symptomatic cardiovascular disease, average to moderately elevated total-C [cholesterol] and LDL-C [bad cholesterol], and below average HDL-C [good cholesterol], MEVACOR is indicated to reduce the risk of:

Myocardial infarction [heart attack]

The term “Primary Prevention” refers to reducing the risk of having a first heart attack.

The professional product labeling for lovastatin was last revised June of 2002.

Pravastatin (PRAVACHOL)

Pravastatin is a top seller with retail sales of $1.6 billion and over 13 million prescriptions dispensed in 2003. This statin was approved by the FDA in October 1991.

The following benefit claims are made in the professional product labeling for pravastatin:

Primary Prevention of Coronary Events

In hypercholesterolemic [elevated cholesterol] patients without clinically evident coronary heart disease, PRAVACHOL is indicated to:

• Reduce the risk of myocardial infarction [heart attack]
• Reduce the risk of cardiovascular mortality [death] with no increase in death from non-cardiovascular causes.

Secondary Prevention of Cardiovascular Events

In patients with clinically evident coronary heart disease, PRAVACHOL is indicated to:

• Reduce the risk of total mortality [death] by reducing coronary death
• Reduce the risk of myocardial infarction [heart attack]
• Reduce the risk of stroke and stroke/transient ischemic attack (TIA)

The term “Secondary Prevention” refers to reducing the risk of having a second heart attack or stroke.

The professional product labeling for pravastatin was last revised November 2003.

Rosuvastatin (CRESTOR)  

This uniquely dangerous statin drug was approved by the FDA in August 2003. We testified before the FDA advisory committee reviewing rosuvastatin urging that it not be approved because of the risk of potentially fatal muscle and kidney toxicity (see Worst Pills, Best Pills News October 2003). We subsequently petitioned the FDA to ban the drug.

At this time no claim can be made in rosuvastatin’s professional product labeling that this statin can reduce the risk of a heart attack or stroke.

The professional product labeling for rosuvastatin was last revised in August 2003.

Simvastatin (ZOCOR)

In 2003, simvastatin was the third-largest-selling drug in the United States. Almost 24 million prescriptions were dispensed at a retail cost of greater than $3.3 billion. This statin was approved by the FDA in December 1991.

The following benefit claims are made in the professional product labeling for simvastatin:

Reductions in Risk of CHD Mortality [coronary heart disease death] and Cardiovascular Events

In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, ZOCOR is indicated to:

• Reduce the risk of total mortality by reducing CHD deaths.
• Reduce the risk of non-fatal myocardial infarction and stroke.

The professional product labeling for simvastatin was last revised November 2004.

What You Can Do

If you must use a statin drug to control your cholesterol, you should use one that has an FDA health benefit claim in its professional product labeling.