Non-Statin Makers May Struggle with New Cholesterol Treatment Guidelines

A task force from the American College of Cardiology and the American Heart Association released the new guidelines to promote the use of statins alone for the reduction of low-density lipoprotein cholesterol (LDL-C), or “bad cholesterol.”

“The ACC/AHA frequently updates treatment guidelines and disease definitions, so the update itself was not surprising,” says Eric J. Dimise, Ph.D., GlobalData’s Analyst covering cardiovascular and metabolic disorders.  “The change in course from historically accepted LDL-C treatment goals and regimens – specifically, the break from the ‘treat-to-target’ approach for LDL-C reduction and the ‘statins only’ recommendation – is what was surprising and, consequently, is one of the major reasons this story is still making headlines.  This change represents a philosophical shift in the long-term treatment of patients with ASCVD.  As many reports on the subject have highlighted, the repudiation of the treat-to-target approach asks physicians to shift away from a well-established, time-tested protocol that has even become ingrained in medical school curricula. So, the fact that the cardio community is far from achieving consensus is what is not surprising.”

Instead of employing a “treat-to-target” approach to cholesterol reduction, the new guidelines promote a more opaque goal of “treat to reduce risk,” with an increased emphasis on healthy lifestyles.  Dr. Dimise told Med Ad News Daily, “The physicians will sort out whether or not they ought to achieve consensus. My feeling is that these guidelines will start – actually, they already have started – a robust debate in the cardio community as to the role and the extent to which outcome and event-based clinical trials should impact the use of lipid-lowering therapies.  The guidelines propose that statins should be the only therapy used for LDL-C reduction because they are the only drugs that have proven, time and again, that they are capable of reducing the risk, or rate of occurrence, of adverse cardiovascular events (e.g. heart attack). One camp touts this as vigorous, evidence-based science.  They aren’t wrong. Another camp argues that, vigorous and evidence-based as the guidelines may be, the correlation between LDL-C levels and occurrence of cardiovascular events is clearly established and that the time-tested, treat-to-target approach to LDL-C reduction provides clear goals and delivers good results for patients in terms they can understand. From media coverage and discussions with GlobalData key opinion leaders, the general response to these guidelines seems to be that physicians will ultimately do what they believe is in the best interest of their patients, taking into account medical history, response to drugs, lifestyle factors, and so forth.  Consensus will not be achieved for its own sake, and given the emphasis on making good choices for individual patients; a one-size-fits-all philosophy – if this is what we mean by ‘consensus’– is very unlikely and, in my estimation, does not reflect the intentions of the authors of the guidelines.”

Dr. Dimise also took into consideration the potential long-term impact of the new guidelines.  “Stepping back for a moment, the long term impact of these guidelines may be a shift in emphasis in the medical community towards outcomes-based clinical trials, viewing them as a more rigorous proof of efficacy of a drug relative to biomarker-based trials (lowering of LDL-C serum levels, for example),” he told Med Ad News Daily. “In other words, if these guidelines mark a philosophical shift in the community, then their impact will be larger than if all cardiologists convert to the recommendations found in these specific guidelines.  After all, guidelines get updated and revised, but if they can bring about a shift in the way physicians view the overall goals and standards for LDL-C therapeutic care, then we’re looking at a potentially long-term impact within, and potential beyond, the LDL-C treatment paradigm.  Lastly, physicians are having a hard time achieving consensus on more than one issue in these guidelines. Should the “statins only” stance be adopted? I think this issue will be debated for a very long time and will probably never achieve a clean consensus.  There has also been much talk about the ‘risk calculator’. This is an issue that is more likely to be discussed and tweaked, resulting in a tool that a larger percentage of the community can be comfortable with using.  Once an individual is deemed at risk of a cardiovascular event, how doctors will decide to treat them is still murky – and will likely remain so – regardless of the new guidelines.”

The manufacturers of other lipid-lowering drug classes may have their work cut out for them. “Minimally, new LDL-C lowering drugs will need to demonstrate the ability to lower serum LDL-C on a level comparable with statins, if they hope to be competitive at all,” Dr. Dimise told Med Ad News Daily.  “Even then, the cost-effectiveness of generic statins will be difficult to compete with, setting aside the fact that they are already established as the “go-to” therapy for LDL-C reduction.  With these new ACC/AHA guidelines, the clinical community appears to be shifting towards an outcomes and events-based mindset for new – or old – lipid drugs.  We also see this in the FDA.  Consider the ongoing IMPROVE-IT trial with Vytorin and Zetia and the decisions handed down in October regarding Amarin’s triglyceride therapy Vascepa and the ANCHOR trial.  Given all of these factors, I would counsel manufacturers to strongly consider performing rigorous, outcomes-based Phase III trials, expensive and time consuming as they might be, as this seems to be the direction regulators and clinicians are moving. In fact, one only has to look at the ongoing PCSK9 Phase III programs to see that this shift may already be occurring.  Given that the dyslipidemia market is so large, and given that the new guidelines will likely expand the “at risk” patient pool, the market opportunity for new drugs is definitely there.  So, drug manufacturers that make the big investments up-front – that take the time to prove that they’re providing a therapy that can deliver a real clinical benefit – have a decent chance of carving out a sizable slice of the market.”

REFERENCE:  Pharma Live; December 2013; Mia Burns

Leave a Comment