Early combination lipid-lowering therapy with statins and ezetimibe significantly improves prognosis after myocardial infarction compared with later adding ezetimibe or not giving it at all, a study finds.
Current treatment guidelines recommended giving statins immediately after a myocardial infarction to lower low-density lipoprotein cholesterol (LDL-C) levels, researchers from Sweden’s Lund University and the UK’s Imperial College London wrote in the Journal of the American College of Cardiology.
However, most patients needed an additional therapy, such as ezetimibe, to reach target lipid levels, and this ‘stepwise’ approach to additional lipid-lowering therapy often meant a delay in patients attaining recommended LDL-C levels.
The researchers used Swedish registry data from almost 36,000 lipid-lowering naive patients hospitalised between 2015 and 2022 for myocardial infarction and discharged on a statin. They conducted statistical modelling to emulate a trial comparing cardiovascular outcomes and cardiovascular death from three lipid-lowering strategies.
Outcomes were analysed for 6,040 patients (16.9%) who received statins and ezetimibe within 12 weeks of a myocardial infarction, compared with 6,495 patients (18.1%) who received statins with ezetimibe added at between 13 weeks and 16 months post-myocardial infarction, and a final group of 23,291 patients (65%) who only received statins.
Benefits of early combination therapy
They found ezetimibe combination therapy, either early or late, resulted in a greater proportion of patients reaching an LDL-C of <1.4 mmol/L compared with no add-on ezetimibe.
Early combination therapy was associated with a greater absolute and relative benefit in terms of major adverse cardiovascular events (MACE) compared with delaying combination therapy.
The researchers highlighted that approximately two-thirds of patients had not received add-on therapy with ezetimibe by 16 months post-myocardial infarction, and those patients experienced the highest risk of MACE and death.
Using the study population, they modelled that if 100% of patients received ezetimibe early, an estimated 133 myocardial infarctions could be avoided in a population of 10,000 patients in three years.
In the UK, which has an estimated 100,000 hospital myocardial infarction admissions annually, this would equate to an estimated 5,000 myocardial infarctions being prevented over a 10-year period.
Preventing myocardial infarction with ezetimibe
Professor Margrét Leósdóttir, associate professor of internal medicine at Lund University and senior cardiology consultant at Skåne University Hospital, Malmö, Sweden highlighted that guidelines recommend the stepwise addition of lipid-lowering treatment with ezetimibe.
‘But it’s often the case that this escalation takes too long, it’s ineffective and patients are lost to follow-up,’ she said.
‘By giving patients a combination treatment earlier, we could help to prevent many more heart attacks.’
Combination therapy was not being applied up-front because it was not included in guidelines and clinicians were cautious about potential side effects and overmedication.
‘However, there are positive effects from applying both medicines as soon after the infarction as possible. Not doing this entails an increased risk,’ Professor Leósdóttir said.
‘In addition, the drug we have examined in the study causes few side effects and is readily available and inexpensive in many countries.’
Professor Leósdóttir hoped the research would provide support for changes in the recommendations to include early initiation of ezetimibe, and she noted a treatment algorithm had already been introduced at Skåne University Hospital with positive results.
Patients had achieved their treatment goals earlier and two months after the myocardial infarction twice as many patients have reduced their bad cholesterol to the target level, compared with outcomes under previous practice.
Post-myocardial infarction care pathways ‘must change’
Co-investigator Professor Kausik Ray, professor of public health at Imperial College London’s School of Public Health, UK, said post-myocardial infarction care pathways must change given the study results.
‘Our findings suggest that a simple change in treatment guidelines could have a huge impact on patients and reduce the demand on the NHS. Ezetimibe is already widely available and prescribed for relatively low cost,’ he said.
‘This add on therapy could be rolled out for around £350 a year per patient, which is a huge cost saving compared to the lasting impacts of treating heart attacks and the impact they have on patients’ lives.’
Previous research by Sweden’s Uppsala University using the Swedish National Prescribed Drug Registry found that women were less likely than men to be prescribed cholesterol-lowering drugs despite identical guidelines, with 5% of women treated with statin plus ezetimibe compared with 8% of men.
