Concerns over statins advice

Earlier this month, the Journal of the American Medical Association (JAMA) published two studies and an editorial supporting the controversial American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management. These 2013 guidelines determined that almost half of Americans between 40-75 years of age are now eligible for cholesterol-lowering treatments called statins.

In the first study, 2,435 participants from Framingham, Massachusetts, were followed for nine years and cardiovascular disease (CVD) outcomes such as heart attack, coronary heart disease and stroke were assessed. Among this study sample, 39% of participants were statin-eligible under the new guidelines compared with 14% under the old, but a similar percentage of participants under either guideline developed CVD (6.3% v. 6.9%). Only 1% of those ineligible for the new guidelines developed CVD, compared with 2.4%.

In the second study, the cost-effectiveness of this approach was analysed by simulation. Under the ACC/AHA guidelines, implementation was expected to cost $37,000 for each additional year of life gained – well under traditional thresholds of cost-effectiveness. Moreover, the study concluded that further expansion of the treatment guidelines to two-thirds of American adults might also be cost-effective, depending on the threshold for cost-effectiveness.

The two papers were joined by an editorial from Dr Philip Greenland and Dr  Michael Lauer, two prominent cardiovascular epidemiologists, which concluded: “There is no longer any question as to whether to offer treatment with statins for patients for primary prevention, and there should now be fewer questions about how to treat and in whom.”

Concerns

Not so fast. My lab at Duke, headed by Dr Michael Pencina, published the original equations used to estimate CVD risk and the estimations of statin eligibility under the ACC/AHA guidelines, and among our group, there is general agreement that yes, more people are likely to be treated with therapeutic benefit and at reasonable costs. Importantly, the guidelines do represent a crucial paradigm shift from lowering cholesterol levels below a static value to lowering a patient’s personalised risk for CVD events and mortality, a welcome departure from more conventional approaches that emphasise biomarker reduction, which may or may not impact disease progression.

However, I would also emphasise caution – if nothing else than because the implications of these results are staggering. As a future physician, I am essentially urged to recommend daily, life-long medication for up to two thirds of adults, many of whom may never have a heart attack for the rest of their lives, and many of whom will experience the debilitating side effects of muscle damage and fatigue (which were not accounted for in these studies). Furthermore, as a profession we seem to have concluded that patients will never adhere to the lifestyle recommendations of diet and exercise and have instead decided to use chronic medications for largely preventable conditions – an astounding defeat for public health.

There are several other concerns, such as the exact risk threshold that should determine statin eligibility; the reliance on mainly white study participants (African Americans, for example, are known to have physiological differences, such as salt sensitivity, that mediate cardiovascular health); and the possibility of financial conflicts of interest between the committee that established these guidelines and BigPharma (seven of 15 people on the committee have financial ties). However, these criticisms are relatively minor when compared to the fact that these studies are not randomised clinical trials, but are retrospective cohort studies and simulations – hardly the gold standard for deciding treatment plans for millions of people.

Frankly, I’m surprised about how quickly these guidelines have caught on. Last year during my cardiovascular pharmacology course, we regularly used the “risk calculator” recommended by the ACC/AHA guidelines to determine statin prescriptions; just last week, I shadowed a family physician who pulled up the risk calculator during a patient visit to determine her patient’s statin eligibility (it should be noted that on the same day, I also met a patient who experienced the side effects associated with statins use).

At the very least, there is a significant proportion of physicians who use these guidelines in everyday practice. Although the evidence thus far has supported the population-based approach to reducing CVDs, the primary cause of death worldwide, I would only re-emphasise the importance of clinical caution: statins eligibility is not a closed case just yet, and it may take some time before we fully understand how statins can be best prescribed.

Any views or opinions expressed in this article are solely those of the author.

*Jerry Lee [2013] received an MPhil in Epidemiology as a Gates Cambridge Scholar and is now a second year medical student at Duke University. He is currently funded by the American Heart Association to conduct statins research with Dr Michael Pencina. Picture credit: "Crestor Tablets (rosuvastatin)" by Mk2010 – Own work. Licensed under CC BY-SA 4.0 via Wikimedia Commons.