Patients at high risk for cardiovascular events who had the highest blood eicosapentaenoic acid (EPA) levels one year after daily intake of omega-3 carboxylic acid, a prescription fish oil, had similar rates of major cardiovascular events to those who took a corn oil -Placebo based on a secondary analysis of the STRENGTH study presented at the American College of Cardiology’s 70th annual scientific meeting. The researchers also found no increase in cardiovascular events in patients with the highest levels of docosahexaenoic acid (DHA) compared to placebo.
The impetus for this post-hoc analysis was the further investigation of the strikingly different results between STRENGTH and REDUCE-IT, another large, randomized clinical study in which a different omega-3 fatty acid formulation (only icosapent-ethyl, purified EPA) and mineral oil were used as a placebo.
“This is an extremely controversial area. One fish oil trial after another was neutral, but REDUCE-IT reported a remarkable 25% reduction in events compared to a placebo pill containing mineral oil. However, in our analysis, this was confirmed at Patients Treated With Fish Oil We found no evidence that EPA is beneficial or harmful to DHA, “said Dr. Steven Nissen, MACC, cardiologist at Cleveland Clinic and lead author of the study. “So we have a lot of patients taking fish oils, but no evidence that they are beneficial for the heart.”
Between October 30, 2014 and June 14, 2017, 13,078 people at high risk for major cardiovascular events at 675 locations in 22 countries took part in the double-blind, multicenter STRENGTH study. The patients were randomized to receive either four grams of omega-3 carboxylic acid daily (a combination of EPA and DHA) or corn oil as a placebo. As previously reported, the researchers found no difference between the two groups in terms of the primary outcome – a combination of cardiovascular death, heart attack, stroke, need to open blocked arteries, or chest pain that required hospitalization.
This remained the case in the current analysis, in which a subgroup of 10,382 patients (5,175 on the omega-3 carboxylic acid and 5,207 on the corn oil group) with available omega-3 fatty acid levels were examined. Events occurred in 11.1% of patients treated with fish oil and 11% of patients in the placebo group. Overall, this group of patients was on average 62.5 years old, one third were women and another third had diabetes.
The researchers grouped the patients into thirds (tertiles) based on the EPA and DHA levels achieved, which were determined through blood tests at the start of the study and 12 months after randomization. The mean plasma EPA levels for patients taking fish oil were 89 (46-131) μg / ml and 91 (71-114) μg / ml for DHA, with the upper tertile values of 151 (132-181) and 118 (102) reached -143) µg / ml.
The researchers found no difference in the occurrence of the given primary result in patients treated with omega-3 carboxylic acid who were in the upper tertile of the EPA values achieved after one year compared to events observed in patients who were treated with corn oil. The event rate was 11.3% and 11%, respectively. For the top tertile of the DHA achieved, the event rate was 11.4%. The researchers said they expected events in these patients would be different if higher EPA levels played a protective role. Further analysis looked at changes in EPA or DHA over time and similarly showed neutral effects on cardiovascular outcomes.
“To be thorough, we examined the data in a number of ways – absolute EPA and DHA levels, changes in levels of these omega-3 fatty acids, levels of red blood cells, and by subgroups of primary and secondary prevention,” said Nissen. “None of these analyzes showed any advantages or disadvantages.”
Nissen said there are several possible reasons for the very different results emerging from the STRENGTH and REDUCE-IT studies.
“It could be that EPA is really beneficial, or it could be that the administration of DHA in STRENGTH caused harm, undermining the benefits of EPA. However, the current study found no benefits from EPA and no harm from DHA “said he said. “Alternatively, the different results of these studies could have occurred because REDUCE-IT used mineral oil as a placebo, resulting in a false positive study. Unlike corn oil, which is inert, mineral oil has serious adverse effects. If you give a poison placebo then the active ingredient can look really good. “
In the STRENGTH study, the upper tertile of the mean EPA level achieved was 151 μg / ml, which is favorable compared to the median value given in the REDUCE-IT study (144 μg / ml).
Nissen said if there is no benefit from fish oil in preventing serious cardiovascular events, the potential harm must be considered. Although the absolute numbers were small, newly onset atrial fibrillation, a dangerous heart rhythm disorder, increased 69% in those taking fish oil, which occurred in 2.2% of patients in the fish oil group compared to 1.3% of those taking corn oil .
“Fish oils significantly increase the risk of atrial fibrillation, and there is no solid evidence that they help the heart anyway,” said Nissen. “It’s a sad story for cardiology.”
A major limitation of the study is that it is a post hoc analysis.
This study was simultaneously published online in JAMA Cardiology at the time of presentation. The original STRENGTH study was funded by AstraZeneca.
Nissen will be available to the media in a virtual press conference on Sunday, May 16 at 9:45 am ET / 1:45 pm UTC.
Nissen will virtually present the study “Relationship Between Omega-3 Fatty Acid Levels and Serious Adverse Cardiovascular Outcomes in High Cardiovascular Risk Patients” on Sunday, May 16 at 8:00 am ET / 12:00 pm UTC.
ACC.21 will take place virtually from May 15-17, bringing together cardiologists and cardiovascular specialists from around the world to share the latest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter, and # ACC21 for the latest news from the meeting.
The American College of Cardiology envisions a world where innovation and knowledge optimize cardiovascular care and outcomes. As a professional home for the entire cardiovascular care team, the mission of the college and its 54,000 members is to transform cardiovascular care and improve heart health. The ACC awards credentials to cardiovascular professionals who meet rigorous qualifications and are leaders in developing health policies, standards and guidelines. The college also provides professional medical training, disseminates cardiovascular research through its world-renowned JACC journals, operates national registers to measure and improve care, and offers cardiovascular accreditation to hospitals and institutions. More information is available at ACC.org.