A new treatment for coronary atherosclerosis that combines a PCSK9 inhibitor with statin therapy has lowered cholesterol levels in high-risk patients to unprecedented levels marking the start of a new era in lipid lowering management say Australian and US researchers.
Presenting the findings of the GLASGOV trial at the American Heart Association’s scientific meeting in the US last week, Professor Steven Nissen, Department Chair of Cardiovascular Medicine at the Cleveland Clinic in the US who co-directed the study with Professor Stephen Nicholls, Deputy Director and Heart Health Theme Leader at the South Australian Health and Medical Institute, said the study showed that very low LDL-C levels were not only associated with a greater benefit on plaque progression but also promoted disease regression.
“We really only have evidence for disease regression with statins, no other LDL lowering therapy has shown these kinds of benefits,” he said at a press conference.
Conducted at 197 sites around the globe the GLASGOV study enrolled 968 patients presenting for coronary angiography. They had an LDL-C level above 80 mg/dL or in the range of 60-80 mg/dL with additional risk factors.
Patients were randomly assigned to take either statin monotherapy, or a statin together with a monthly self-injection of the PCSK9 inhibitor evolocumab at a dose of 420 mg over 18 months.
Patients in both arms of the trial were had an average baseline LDL-C level between 92 and 93 mg/dL and virtually all patients were already on statins at baseline – with 60% of those patients receiving high intensity doses.
According to Professor Nissen, patients who received the PCSK9 inhibitor in addition to their statin therapy had dramatic reductions in LDL cholesterol levels, down from 93 mg/dL at baseline to 36.6 mg/dL.
He also said that evolocumab-treated patients had a significant reduction in IVUS-measured percent atheroma volume (PAV) compared with patients who received statin monotherapy.
Approximately two-thirds of treated patients had a regression of coronary atherosclerosis.
“We did not regress everybody [in the treatment arm] which shows that there are factors other than LDL-C that drive disease progression,” he pointed out.
Some patients, such as those who started with an LDL cholesterol less than 70 mg/dL, had on-treatment LDL cholesterol levels as low as 24 mg/dL. In that group of patients there was twice as much disease regression.
“That’s pretty much unprecedented,” Professor Nissen said.
“We have never seen levels of regression at that magnitude in any study previously conducted.”
While Professor Nissen stressed that the study was not powered to look at cardiovascular morbidity and mortality outcomes he said that cardiovascular events were “trending in the right direction,” with slightly lower event rates occurring in the group treated to these very low LDL-C levels.
“Clearly, IVUS is a useful measure, but the critical determination of benefit and risk is going to come from the outcome trials,” he said. “We are very humble about this. We know we have a surrogate endpoint—we think this is a signal that suggests there may be benefits at really low LDL [cholesterol] levels, but the definitive studies will come next year.”
While we await those larger studies, Professor Nissen said that the findings from GLAGOV was the first “intriguing” evidence to show that clinical benefits may extend to LDL-C levels as low as 20 mg/dL.
“I thought there might be diminishing returns at very low LDL-C levels and we were perfectly prepared to find that but that’s not we found … instead we found that outcomes just kept getting better – there is continuous reduction in disease progression with no tailing off of benefit at these very low LDL-C levels.”