Better LDL Control After STEMI Means Less Neoatherosclerosis

Patients who reach lower levels of LDL cholesterol in the years following DES implantation for STEMI are less likely to develop neoatherosclerosis, a known cause of stent failure, according to a post hoc analysis of the CONNECT trial.

Not only did patients who achieved target LDL levels have a lower rate of neoatherosclerosis as seen on optical coherence tomography compared with those who did not at 3 years (7% vs 19%; P = 0.02), but also on-treatment LDL cholesterol level was independently linked to the presence of neoatherosclerosis on multivariable analysis (OR 1.46 per 25-mg/dL increase; 95% CI 1.09-2.01).

The key message from the study is that the story is not over once a stent is placed, said senior author Lorenz Räber, MD, PhD (Bern University Hospital, Inselspital, Switzerland). “There’s a double motivation for patients to bring their LDL down, which is first avoiding progression—or even if the LDL values are really low, inducing regression—but then also to assure that the stent will remain free of neoatherosclerosis throughout the long term,” Räber told TCTMD.

The findings are “intuitive,” Allen Jeremias, MD (St. Francis Hospital, Roslyn, NY), who was not involved in the study, told TCTMD. “Placing a stent doesn’t fix the underlying pathophysiology. And so it’s not surprising that under the same circumstances, let’s say without modifying LDL levels or other risk factors, the same disease process would go on even in the presence of a stent. Eventually new plaque will form in the exact same location as you had before.”

The study is “very positive [and] optimistic,” he continued, because “we now have good tools that we can [use to] modify that specific risk.”

Lower LDL, Clearer Stents

Neoatherosclerosis is similar to native atherosclerosis, but it develops much faster, Räber said. “It takes 1 to 5 years until new mainly lipid-rich plaques inside the neointima—that’s the skin that covers the metallic stent—form. And this is one of the key reasons why not only restenosis, but importantly also stent thrombosis, occurs. So more than a third of late occurring stent failures are due to this phenomenon called neoatherosclerosis.”

Previous retrospective data have suggested that LDL may play a role in neoatherosclerosis, but the new study, published online last week in JAMA Cardiology with first author Jonas Dominik Häner, MD (Bern University Hospital, Inselspital), represents the first prospective look at this phenomenon, said Räber.

The researchers included 178 Swiss and Japanese patients (mean age 63.4 years; 15% female) from the CONNECT trial who underwent OCT at 3 years following PCI with DES for STEMI. Just over one-half (55%) had achieved their target LDL cholesterol level by that time, and 45% had not, with respective mean on-treatment levels of 48 and 87 mg/dL.

Patients who achieved the target LDL level at 3 years had lower baseline levels of total and LDL cholesterol compared with those who did not. Mean LVEF also was greater.

There were no differences in prescriptions of high-intensity statins, with 92% of patients overall receiving them at discharge. However, at 3 years, more patients who achieved the target LDL cholesterol level were using high-intensity statin therapy (89% vs 69%; P < 0.001) or P2Y12 inhibitors (54% vs 38%; P = 0.03) compared with those who did not, but there was no difference in ezetimibe use (51% vs 45%; P = 0.45).

Overall, 12% of patients had neoatherosclerosis at 3 years on OCT. The odds of this outcome were greater in patients who did not meet LDL treatment targets (OR 3.0; 95% CI 1.19-8.24). Neoatherosclerosis was seen across the range of country-specific LDL target recommendations: 8% of patients with LDL < 55 mg/dL, 11% with LDL 55 to < 70 mg/dL, and 19% with LDL ≥ 70 mg/dL (P = 0.22).

At 3 years, mean on-treatment LDL cholesterol levels were higher in patients with versus without neoatherosclerosis (83 vs 63 mg/dL; P = 0.005), and high-intensity statin prescriptions were less common (55% vs 83%; P < 0.001).

Besides reaching on-treatment LDL targets, there were no other independent predictors of neoatherosclerosis in the study.

While the analysis is relatively small, Räber said the findings are clear. “If you want to keep your stent healthy, you need to bring your LDL down below the guideline-endorsed thresholds,” he said. That they were able to show such a substantial association across multiple patient populations and during a time before the availability of PCSK9 inhibitors only strengthens the findings, he said.

For Jeremias, the solution for these patients is intensive lipid-lowering alongside lifestyle changes. The study “demonstrated that the lower you go, the better it is,” he said, adding that he personally aims for 55 mg/dL in these patients. “If you have disease that requires a stent, . . . the risk factor management should be such that we are as aggressive as we possibly can be. Get the LDL super low, not just to 70.”