Statins Work But Pharmacoeconomic Caveats Abound

	LDL- and triglyceride-lowering of the branded statins is currently superior to the generic statins.

Cardiologists need to weigh the benefits of the more efficacious branded statins in comparison to the less expensive generics.

There’s no denying the popularity and efficacy of statins to control high cholesterol. The area of professional disagreement centers on whether prescribing preventative statin therapy is cost savings as well as cost effective.

While people often say that preventative treatment is cheaper than having an event occur, that is not always factual, according to Michael Koren, MD, director of noninvasive cardiology at Memorial Hospital Jacksonville, healthcare economist, and director of research for Jacksonville Center for Clinical Research in Florida. In many circumstances, the preventative treatment is a cost-effective measure, meaning the cost of preventing a heart attack seems reasonable. Yet, the overall healthcare system may not be saving money due to the preventative measures, which he defines as cost-savings.

“The two concepts are quite different, and yet often confused,” Koren says.

To further elucidate the contentious issue of preventative therapies, Koren defines the three levels of healthcare investment. The first level is when an upfront investment actually saves money in the long term, meaning the amount that is saved in downstream costs is greater than the initial investment. The first level occurs very infrequently in medicine and pharmacoeconomic analyses. The second, more common investment is when the upfront investment will decrease the cost downstream, but not to the extent that the entire upfront investment is recovered.

“The reason for that is we are not perfect at anticipating who will have a heart attack,” he says.

As many studies suggest, cardiologists have to treat 20, 30 and even 100 people to prevent one heart attack. In this scenario, the cost of treating 100 people to prevent one heart attack is cost-effective, meaning it is a good use of funds. It is not, however, cost-savings because it does not conserve money for the overall system, Koren says.

The third level of healthcare investment presents a circumstance that is neither cost-effective nor cost-savings. An example would be to treat everyone that was 20 years old for hyperlipidemia. Statistically, lowering everyone’s blood pressure by five points would be a positive outcome. However, from a practical and financial standpoint, the downstream rewards wouldn’t be worth the cost in dollars, Koren says.

From an epidemiological standpoint, individuals are reaping the benefits of hyperlipidemia medications. The cholesterol levels in the U.S. have fallen to an ideal range of 199 in 2007, compared to 222 in 1960, according to figures from the Centers for Disease Control and Prevention. The CDC attributes the improvement to anti-cholesterol drugs.

“If you look at all the data, heart attack rates are dropping steadily, bypass surgery rates are dropping steadily, and cholesterol-lowering drugs are a huge part of these remarkable and positive changes,” Koren says.


Safety and efficacy

Because of the widespread popularity of anti-cholesterol medications, their safety and efficacy have endured a great deal of public scrutiny. Koren says there is not enough promulgated about the remarkable advances and benefits of the drugs, and too often unlikely side effects are highlighted by the media. If the trend of misinformation is not reversed in the future, there could be an uptick of cardiovascular morbidity and mortality rates as patients refuse to take the drugs out of unwarranted fear.

Regarding side effects, there is a phenomenon of low-level muscle awareness, or muscle aching, that affects about 20 percent of patients. Many of these patients stop the medication as a result. Overall, public perception, reinforced by the media, is scaring patients away from a class of drugs that have very few serious side effects, Koren emphasizes.

Many institutions have some degrees of limitations or therapeutic substitutions that may prohibit a doctor from choosing a statin of their choice. This is not the case for Lipitor because it is unequivocally held as the drug of choice for acute coronary syndrome based on a series of studies. As a result, Lipitor is not restricted in most hospital formularies, he says.

The three top-selling statins on market in the U.S. are typically considered the most effective—Lipitor (Pfizer), Vytorin (Merck/Schering-Plough), and Crestor (AstraZeneca). Koren says that these are significantly more effective than any of the generic statins.

“The LDL-lowering of the branded statins is currently superior, and the triglyceride-lowering of the branded statins is also superior, particularly Lipitor,” Koren says. Physicians need to explain these differences to their patients and patients need to decide if they are willing to pay for the additional efficacy.

Lipitor, which has been on the market the longest, has the greatest outcome research and nearly every study attests to the drug’s safety and efficacy in reducing heart attacks, strokes, and other cardiovascular complications, Koren says. Vytorin and Crestor do not yet have this type of outcomes background.

While Vytorin, a combination of simvastatin and Zetia, has had some positive outcomes regarding simvastatin, the gap of efficacy in the Zetia, or non-statin, component is still unclear, Koren says.

“Vytorin probably does a little better than Lipitor in lowering LDL, but there is still a lingering doubt about using a non-statin mechanism for lowering LDL,” he says.

In addition, simvastatin has more drug interactions than Lipitor. For example, it is contraindicated with the use of Amiodarone, an antiarrhythmic agent.

Merck/Schering-Plough recently reported the results of the ENHANCE trial, which found that Vytorin was no more effective in treating patients who were genetically predisposed to having dangerously high levels of cholesterol than Merck’s drug Zocor because it did not slow the growth of artery blockages.

Crestor is somewhat more effective at lowering LDL levels than Lipitor, but it has the least amount of outcomes data, Koren says. He adds that some of the clinical research that has been published about Crestor has not been uniformly positive. He specifically referenced the CORONA trial that was released at last year’s AHA Scientific Sessions in Orlando, Fla., in which Crestor did not meet its endpoint of showing benefit with congestive heart failure patients, though some confounding factors may have interfered with its results, such as the European patients in the study were dying from factors other than heart attacks.

Merck & Company recently failed its third attempt to gain FDA approval to sell its generic simvastatin over-the-counter (OTC), which would create a much larger market for the company. Koren says that the FDA has historically resisted the efforts to sell drugs over-the-counter that require consultations with a professional. He says that a change of the type of self-prescription would require a change in U.S. healthcare model, in which the patient would have a much more proactive role for treatment that requires chronic therapy.

“The ongoing battle is between having greater outcomes data and more efficacy compared to what people want to pay,” Koren concludes.