Just One-Third of European Patients Get to LDL Cholesterol Goals

A large number of European patients with and without atherosclerotic cardiovascular disease (ASCVD) are receiving inadequate lipid-lowering therapy, with the majority of patients receiving only moderate-intensity statins and very few treated with concomitant therapy, such as ezetimibe or PCSK9 inhibitors, according to the DA VINCI study.

As a result, most primary and secondary prevention patients aren’t getting to the recommended LDL-cholesterol targets as outlined in the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidemia guidelines. In fact, even when using the cholesterol targets in the older 2016 ESC/EAS guidelines, which recommended a higher LDL target, only half of patients are getting to goal.

“There are clear gaps between the ESC/EAS guidelines and goal attainment in Europe based on how we are practicing at the moment, with only 54% of patients achieving the 2016 risk-based LDL-cholesterol goal,” said Kausik Ray, MD (Imperial College London, England), during a virtual presentation at the 2020 EAS Congress. “That number is even worse when we look at the 2019 guidelines, with only about one-third achieving the goals.”

With the European guidelines, LDL-cholesterol targets are based on the patient’s 10-year risk of ASCVD. Under the 2016 guidelines, the target for low- and moderate-risk patients is less than 3.0 mmol/L (or 116 mg/dL). In the high-risk and very-high-risk patients, though, it is recommended physicians aim for a 50% reduction in LDL cholesterol or achieve a target of less than 2.6 mmol/L and 1.8 mmol/L, respectively (100 mg/dL and 70 mg/dL).

With the 2019 guidelines, the goal for low-risk patients is similar to the previous recommendation, but elsewhere the targets are lower. For the moderate-risk patient, the treatment target is less 2.6 mmol/L (100 mg/dL). For the high-risk and very-high-risk patient, the goal is now a 50% reduction and an LDL level of less than 1.8 mmol/L and 1.4 mmol/L (70 mg/dL and 55 mg/dL), respectively. And finally, for the very-high-risk patient who has had a second cardiovascular event within 2 years, the goal is a 50% reduction and an LDL cholesterol level of less than 1.0 nmol/L (39 mg/dL).

“We match the LDL levels to the level of risk,” said Ray regarding the cholesterol guidelines.

With DA VINCI, an observational study of 2,888 primary-prevention and 3,000 secondary-prevention patients, the researchers sought to evaluate the current use of lipid-lowering therapies across a broad range of patients from 18 European countries. The primary outcome of the study was the number of patients who achieved the 2016 ESC/EAS cholesterol targets, but the researchers also included the 2019 targets after they were updated last year.

Low LDL Targets in High-Risk Patients

Overall, 28%, 52%, and 4% of patients were treated with a high-, moderate-, and low-intensity statin, respectively, while just 9% received ezetimibe in combination with other lipid-lowering therapy and only 1% received combination therapy with a PCSK9 inhibitor. In terms of goal attainment, only 33% of primary- and secondary-prevention patients got to goals stipulated in the 2019 ESC/EAS cholesterol guidelines.

There are clear gaps between the ESC/EAS guidelines and goal attainment in Europe based on how we are practicing at the moment. Kausik Ray

For patients with established ASCVD, 38%, 44%, and 2% were receiving monotherapy with a high-, moderate-, and low-intensity statin. Similarly, only 9% received combination therapy with ezetimibe and 1% received a PCSK9 inhibitor. In the secondary-prevention patients, just 30% had their LDL levels treated to the 2016 targets and 18% got to goal under the more recent cholesterol guidelines. With use of higher-intensity statins, as well as with ezetimibe, more patients got to the recommended targets, but such an improvement wasn’t observed when using the tougher 2019 recommendations as the target.

Ray said that unless a PCSK9 inhibitor was used, roughly 80% of patients with ASCVD are not going to get to the LDL targets. For those who received a PCSK9 inhibitor, 67% and 58% achieved the LDL goals outlined in the 2016 and 2019 guidelines, respectively.

In primary prevention, the vast majority of low-risk patients treated with any of the therapies achieved the recommended LDL goals. Even in moderate-risk primary prevention, most patients achieved the 2016 and 2019 cholesterol targets with statin monotherapy. However, in the high-risk and very-high-risk patients, goal attainment “tends to fall away” with many of the treatments, Ray said. For example, while 63% of high-risk patients treated with a moderate-intensity statin got to goal under the 2016 guidelines, only 29% achieved the targets in the 2019 guidelines. Similarly, only 22% of high-risk patients treated with a high-intensity statin got to 2019 cholesterol goals.

During the presentation, Ray noted that average LDL cholesterol with moderate-intensity statin therapy—the predominant treatment in both primary and secondary prevention patients—was 2.31 nmol/L (89.3 mg/dL). With high-intensity statins, the average on-treatment LDL level was 2.18 nmol/L (84.3 mg/dL).

“Even if moderate-intensity statin therapy were optimized to high-intensity, we can see that when you move the goals to very low levels, [treatment] will still be insufficient because of how high baseline LDL levels are—it’s above 2.0 mmol/L—making it almost impossible without combination therapy to achieve those goals,” said Ray. “And in particular, if we look at 1.4 mmol/L as the target for those very-high-risk patients, only about 18% achieved those goals overall. In part, that reflects underutilization of combination therapy.”