New cholesterol guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC) recommend adding ezetimibe and/or PCSK9 inhibitors to statin therapy for select high-risk patients, and also propose using coronary artery calcium scoring as “a tiebreaker” to guide statin decisions for those at intermediate risk of atherosclerotic cardiovascular disease (ASCVD).
“How we treat and how we prevent (CVD) can vary from patient to patient,” said ACC vice president Richard Kovacs, MD. “This guideline gives clinicians the tools that we need to have those conversations with patients about the most appropriate treatment for high cholesterol.”
It wades deeper into the issue of cost-effectiveness than the last guideline in 2013—particularly regarding the role of PCSK9 inhibitors—and provides clinicians with two tools to personalize patient risk beyond their estimated 10-year ASCVD risk.
One of those tools is the inclusion of “enhancing factors” such as metabolic syndrome, premature menopause, chronic kidney disease and inflammatory disorders, among others, which may push an individual toward a stronger recommendation for statin therapy. The other is coronary artery calcium (CAC) measured by CT, with a score of zero indicating that statin therapy can be safely withheld in patients with borderline or intermediate risk—those at 5 to 7.5 percent and 7.5 to 19.9 percent risk of ASCVD within 10 years, respectively. But even in the absence of CAC for these patients, the presence of risk-enhancing factors may favor statin therapy.
And once any treatment is started, whether that involves lifestyle modifications or drug therapy, the authors suggest a fasting lipid test at four to 12 weeks to assess effectiveness and adherence. Further lipid tests should be scheduled every three to 12 months after that, depending on the patient.
Inclusion of new nonstatin therapies
The updated guidelines make room for nonstatin therapies such as ezetimibe and PCSK9 inhibitors for the first time, but their role is fairly limited.
The authors recommended these therapies only in patients considered “very high risk,” which encompasses those with multiple ASCVD events like stroke, MI or acute coronary syndromes—or those with one major ASCVD event and multiple high-risk conditions. They suggest maximally tolerated statin therapy as a first-line defense, but if LDL cholesterol remains above 70 mg/dL, ezetimibe is a reasonable next step, according to the guidelines. If that doesn’t sufficiently lower LDL, PCSK9 inhibitor injections could be considered.
“Statins are where you begin. A very important point that I think could be made is that many patients … are not taking their statins as often as some doctors say they do,” said Neil J. Stone, MD, vice chair of the guideline writing committee and a professor at Northwestern University Feinberg School of Medicine.
“We use a stepwise approach with ezetimibe because that will reduce the number of patients that are taking a therapy (PCSK9 inhibitors) that at mid-2018 list prices … were still not of good value.”
The makers of PCSK9 inhibitors have recently cut their list prices significantly, so it remains to be seen whether their new role in the guidelines and the price changes expand access to these treatments.
“As someone who prescribes these medications, I can point to this recommendation and say, ‘I think it’s valid,’” said Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital. “But I’m not sure how the insurers will interpret cost-effectiveness because cost-effectiveness is really a societal thing; it has nothing to do with an individual patient. If a patient and a provider think it’s beneficial to a patient, if it’s a million dollars, the patient’s still going to want it.
“It will be complicated, but it’s definitely not going to open the floodgates” to more PCSK9 prescriptions, he said.
Natarajan said the cardiology community has been waiting to see how the guidelines framed PCSK9 use and how it might alter the access picture for patients.
“The elephant in the room is the sticker price but what people forget is that if the sticker price goes down, that doesn’t necessarily mean the copay goes down,” he said. “For our patients, the most important part is actually the copay part. The second part, which is hidden, is that the sticker price sort of translates to access and how willing insurers will be in releasing the medicines.”
Natarajan predicted insurers still will restrict access to these prescriptions to a point, but said access may improve for patients who meet the granular criteria for PCSK9 inhibitors proposed in the guidelines.
Greater use of CAC scoring
While stressing that the document doesn’t recommend widespread screening for CAC, Stone said the imaging technique is “the best tiebreaker we have now” when the risk-benefit balance is uncertain.
“Most should get a statin, but there are people who say, ‘I’ve got to know more, I want to personalize this decision to the point of knowing whether I really, really need it.’ … There are a number of people who want to be certain about where they stand on the risk continuum and that’s how we want to use it,” Stone said.
Natarajan found this element of the guideline interesting because previous updates have focused on broadening the statin-treated population, while this approach offers a way to narrow it. He added that CT scans for CAC typically aren’t covered by insurers for asymptomatic patients and can cost between $100 and $400 out-of-pocket depending on the institution.
“I hope that with the inclusion in the guidelines that maybe insurers will start to think about paying for it in that setting. … Preventive medicines run lifelong potentially,” Natarajan said. “If you can say that someone who is estimated to be at high clinical risk, that they don’t need to be on a statin because the calcium score is zero, that may be cost-saving because you’re not prescribing the statin for five to 10 years in that individual.”
Natarajan said the emphasis these guidelines placed on CAC screening could enable that recommendation to reach more primary care providers, who would be largely responsible for implementing this primary prevention technique. Previous guidelines have mentioned coronary calcium tests but haven’t included them as top-line recommendations the way the new document does, he said.