AHA 2018 — Expert Commentary: Understanding major changes in CVD prevention

  • Aviva Schwartz
  • Clinical Essentials
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An excerpt from a presentation by Christopher Cannon, MD.

Dr. Cannon is the Education Director of Cardiovascular Innovation at the Brigham and Women's Hospital in Boston, MA.

Cholesterol guidelines: What's new

The 2018 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines have been long awaited. It's been 5 years since the 2013 guidelines, in which the focus was largely on use of statins in specific groups at risk for coronary disease, notably, those with atherosclerotic cardiovascular disease (ASCVD), very high low-density lipoprotein (LDL) levels, and patients with diabetes, and then using the risk score to determine the higher-risk primary prevention patients.

What was absent, and thus long awaited, in these new 2018 guidelines was the use of nonstatin therapies. This was nicely added with both ezetimibe and PCSK9 inhibitors with the evidence that's come out since that 2013 guideline; notably, from the IMPROVE-IT trial, as well as the FOURIER and ODYSSEY Outcomes trials.

The guideline calls for intensifying statin therapy first for those with ASCVD and then looking at the response, making sure that patients are adherent, and so on, and all that was part of the prior guideline. But now if the LDL is above 70, then you would add ezetimibe to try and lower the LDL further. In very high-risk patients, the guidelines note that one would add a PCSK9 inhibitor after having added ezetimibe to try and again get the LDL below 70.

As such, I think this is a nice step forward to incorporate the nonstatin therapies. There'll be, undoubtedly, much debate on the slight nuances, but the big picture is a very good one, where we start using the LDL as a threshold, and if it's above 70 in high-risk patients, you'd add therapy.

For primary prevention, that threshold is more at a 100, and one would usually just go with ezetimibe. The PCSK9 inhibitors have not been studied in very many patients without ASCVD.

New guidance in primary prevention

Begin with the ASCVD risk score to see whether the patient is above or below 7.5%, which would be the general cut point for use of statin therapy if above 7.5%. But if there's some uncertainty, especially in the 5.0%-7.5% group; the guidelines now list about 10 different additional risk markers, which would include high-sensitivity C-reactive protein and lipoprotein(a), among others. A big new addition was more emphasis on calcium scoring.

In these borderline-risk patients, the use of calcium scoring can be a very potent way to risk stratify patients. Sometimes you'll get zero, in which case lifestyle would be the key emphasis. Between 1 and 99, one would consider statin therapy. And if it were above 100, then statin therapy would definitely be recommended. And so that's been a useful tool that many of us are using; I am using it, very frequently, in these borderline patients.

Major prevention trials from AHA

I want to mention a few trials. REDUCE-IT really was a landmark trial looking at high-dose eicosapentaenoic acid (EPA)-based omega-3 preparations showing a huge reduction in cardiovascular events, highly significant, in patients who have elevated triglycerides and ASCVD or diabetes plus ≥1 risk factor.

Another big study was VITAL, which looked at low-dose fish oil and found no benefit in >25,000 patients for primary prevention. Note that there was a distinction from the high-dose prescription-based omega-3 EPA-only preparation used in REDUCE-IT. Also, vitamin D at a 2-g dose did nothing for cardiovascular events. This study pointed out helpful negatives and things to not bother with, but has reaffirmed our focus on lowering LDL and lipid management, as dictated in the guidelines.

Finally, a big trial that, frankly, was a surprise to me and many, was EWTOPIA 75, which looked at ezetimibe monotherapy for primary prevention in elderly Japanese adults, so patients aged 75 years or older. This is a group in which the guidelines have traditionally said we have less evidence and generally take a more moderate approach to statin therapy.

Patients were randomly assigned to ezetimibe or placebo and followed for about 5 years, and there was a highly significant reduction in cardiovascular events. I think these results may advance therapies in several ways. This is the second huge outcomes trial for ezetimibe reaffirming what we've seen before, but in this case, as monotherapy. We have no studies at all, and it's been a big question mark whether monotherapy would be effective, and so, that's very helpful.

The study also affirms the benefit of lipid-lowering in the elderly. And so, even the current 2018 guidelines are more modest in their recommendations in those >75 years. And yet, the evidence from IMPROVE-IT showed the biggest benefit in those patients. Indeed, the NIH has requests for applications to do a statin trial in this population, claiming uncertainty, and this trial says that there is big benefit when lipid lowering in patients >75 years.

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