The statin stumper: Are new cholesterol guidelines prudent or overzealous?
Part 1 of a 2-part series
Cardiovascular disease (CVD) is a killer, pure and simple. The latest statistics from the American Heart Association (AHA) show that CVD accounts for 32% of all deaths in the U.S. More than 2,150 Americans die from some CVD-related cause every day – more than from chronic respiratory diseases, strokes, accidents, and diabetes combined.
The news isn’t all bad: CVD-related deaths declined nearly a third between 2000 and 2010 – a drop largely driven by pharmacologic intervention and (some) lifestyle modifications. But how can we expand those gains to the point that CVD becomes a less frightening public health bogeyman?
In 2013, the American College of Cardiology (ACC) and the AHA advanced a bold new approach for tackling that very issue by proposing controversial new guidelines on how to manage cardiovascular (CV) risk, serum cholesterol, obesity, and lifestyle. The cholesterol guidelines have become a particular flashpoint for controversy, since they effectively increase the population of people who should be taking statins.
The question is: will it work?
Lowering the threshold for statin therapy
The main challenge is figuring out how to balance evidence-based risk-reduction strategies with the risk of overtreatment, which comes with its own set of challenges and downsides. Prior to the introduction of the new cholesterol management guidelines, practitioners relied on the 2001 National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines to determine which patients were most likely to benefit from statin therapy.
There are several big differences in the way risk is assessed under the two sets of guidance -- but the big picture difference is that 56 million Americans would be taking statins to reduce their cholesterol levels under the new guidelines, compared to the 43 million individuals who should be taking them based on the 2001 guidelines.
“The big change was moving away from a specific LDL-C target and going to a total risk estimate for initiating statin therapy,” said Dr. Barry Mennen, a physician who regularly sees obese and diabetic patients with many CVD risk factors, in an interview with BioPharma Dive.
Understanding a rapidly shifting treatment paradigm
A lot has changed in CVD treatment over the last 13 years. Many of the top-selling statins have lost patent protection, resulting in widespread access to cheaper generics; Niacin has been disproven as an effective treatment for hypercholesterolemia; and a new statin, Livalo (pilastatin), was introduced in 2009. Add to that the late-stage development of PCSK-9 inhibitors, which feature a different mode of action (MOA) for treating hypercholesterolemia, and it’s clear that not only is awareness growing, but also that research efforts from companies like Amgen, Sanofi, and Regeneron are moving the science forward and shifting the treatment paradigm.
Change is a constant, so it is quite normal that the therapeutic landscape for addressing hypercholesterolemia has shifted. The availability of new longitudinal, epidemiologic and pharmacologic therapy has driven the changing perspective on how CVD risk factors should be addressed.
Framingham versus NHANES
While the 2001 guidelines relied on the Framingham Heart Study data, the 2013 AHA/ACC guidelines used data compiled as part of the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. Researchers used the findings to extrapolate and analyze heart disease risk factors and rates of various types of heart disease. They then used that data to create a risk calculator.
Regardless of which guidelines are used, treatment decisions are based on risk. Clinicians use guidelines and risk calculators to determine what risk a person faces over the next 10 years of experiencing a CV event.
But the threshold for treatment has been drifting downwards. In 2001, the threshold (assuming that a person did not have a history of certain CV events or risk factors) was a 10-year risk of 20%. Now, anyone with a 10-year risk of 7.5% could benefit from statin therapy, according to the 2013 guidelines.
More diversity of data
According to the AHA, compared with the risk calculator developed as part of the 2001 guidance, the updated guidelines are based on a more diverse database, with inclusion of more African Americans, women, and other non-white minority groups. And now that researchers have long-term longitudinal data showing that African Americans and women are at higher risk for heart disease and stroke, factoring in that increased risk to the calculator improves the quality of the evidence.
Compelling though that logic may be, many disagree with this approach. In fact, some experts have gone so far as to argue the risk calculator overestimates risk by almost 100%, presenting the risk of unintended consequences such as overtreatment. Then again, considering its lethality, “Better safe than sorry” isn’t the worst argument when it comes to averting CV risk.
In the second part of this series, BioPharma Dive will present feedback from an experienced practitioner and pharmaceutical industry veteran, Dr. Barry Mennen, on whether the new guidance makes sense -- and who is standing behind it.
- CM Pulse A quick guide to the 2013 ACC/AHA prevention guidelines
- American Association of Family Physicians Should Family Physicians Follow the New ACC/AHA Cholesterol Treatment Guideline?
- CNN New guidelines may put 13 million more on statins