This transcript has been edited for clarity.
Melissa Walton-Shirley, MD: Hi. I'm Melissa Walton-Shirley, and we're coming to you live from the 2022 European Society of Cardiology meeting in Barcelona. We are honored today to have with us Dr Axel Diederichsen, who presented the very interesting DANCAVAS trial. Welcome. Thanks for joining us.
Axel C.P. Diederichsen, MD, PhD: Thanks for inviting me.
Walton-Shirley: This was a 5.5-year outcomes trial of screening and intervention. You started out with 46,000 men aged 65-74 years. You screened for atrial fibrillation with electrocardiography; a noncontrasted CT of the thoracic aorta, abdominal aorta, and iliac vessels — which I thought was quite remarkable and the first time I've seen that done — calcium scoring; screening for peripheral vascular disease; blood pressure check; blood sugar check; and cholesterol level.
Tell me a little bit more about the design of your trial. What did you do with the data from there?
Diederichsen: We identified those 40,000 men in the entire area of a specific part of Denmark. Then we randomized one third to screening and two thirds to no screening. We ended up inviting 16,000 men for the screening trial and approximately 10,500 did attend their screening. We screened for the seven things you described.
The most important one we were looking for was coronary artery calcification. If the calcium score was above the median for age and gender, we would initiate preventive medication, such as a statin and aspirin. I suspect that this made the main difference in this trial, but I can't say for certain because we also screened for aneurysms, peripheral artery disease, atrial fibrillation, and other things, as you mentioned.
Walton-Shirley: I think this is the most positive yet negatively reported trial of this meeting. What were your top-line results? Because you missed your primary endpoint.
Diederichsen: Our primary endpoint was all-cause mortality, which is a tough one. I mean, we can't prevent cancer with this trial, we can't prevent suicide, but we might be able to prevent cardiovascular diseases. Our primary point was all-cause mortality and the hazard ratio was 0.95 with a P value of.06, so very close but not close enough.
Then we have some subgroup analyses that are encouraging because in the age group < 70 years, there was a remarkable decrease in all-cause mortality. The hazard ratio went down to 0.89, so we could reduce risk of dying by 11%.
Walton-Shirley: That's remarkable.
Diederichsen: It is really remarkable. If we had used a composite endpoint of mortality, stroke, and myocardial infarction, which we did not do, then we would have decreased the risk of those events by 7%.
Walton-Shirley: Was your main intervention medication therapy? I noticed that the cost for this trial was relatively cheap, at €207 per person screened. I know the US dollar currently stands up well against the Euro, but you could not get this degree of intense screening performed for $207 in the US. Even so, this trial tells you something about the human condition because you had difficulty getting people to participate even though the screening was free. Is that correct?
Diederichsen: Yes. You mentioned two things here. First, if you look at the cost of the trial, we did do it really cheaply, but I should acknowledge that we did not buy any CT scanners. We got them for free. We did not buy any other imaging machinery. We just paid the staff to do the screening. It might not be fair to say it only cost €207 per person.
If you increase that threefold, which might be more reasonable or more reflective of other countries, we would still have a cost-effective trial if you compare it to other screening, such as breast cancer, lung cancer, colorectal cancer, and so on.
Walton-Shirley: Sure. Can you speak a bit about the safety aspects of this trial? I saw a trend toward increased bleeding.
Diederichsen: Our treatment was mainly aspirin and statin. Of course, you have to bear in mind that there might be a risk of bleeding with aspirin. We saw an increase in severe bleeding, especially regarding intracerebral bleedings, but it was not a significant increased risk. We have to bear in mind that there might be a risk here.
Walton-Shirley: I saw that there was also a trend in reduction of stroke, yet you did not screen the carotids, did you?
Diederichsen: No, we did not screen the carotids. It was not a trend for a reduction in stroke; there was an actual reduction.
Walton-Shirley: There's been heavy criticism about the lack of inclusion of women in this trial, yet you started with women. Can you talk about that?
Diederichsen: We did perform a pilot study. In the very beginning, we included more than 1000 women and 1000 men. When we looked at our findings — did the women have coronary calcification, did they have aneurysms, did they have PAD, and so on — we did not find as much as among the men.
We had to decide on how we should use our money. Should we include a lot of women without any disease? That may be a waste of money. We thought that if we focus on men and it is negative in men, then it would certainly also be negative in women. That was a decision we took. Of course, we will look at the data we have from women, but it's not powered.
Walton-Shirley: If you had it to do over again, what would you do differently about the structure of the trial? Would you do anything differently? Would you select a different primary endpoint?
Diederichsen: First, I would have chosen another endpoint.
Walton-Shirley: And that is?
Diederichsen: Combined all-cause mortality, stroke, and MI.
Walton-Shirley: It would have been positive. Absolutely.
Diederichsen: I regret that. Second, I think we could save some money and just do a CT scan. I can't tell for sure. I would like to just do the CT scan without all the other investigations.
Walton-Shirley: Did patients come in a single day for all this screening or did they come on different days? How much time did it require?
Diederichsen: It was just 1 day. They came and we had made appointments for, first of all, informed consent, then blood pressure meds, then blood samples, and then a CT scan, and then off they would go. It was very quick at around 1 hour.
Walton-Shirley: Wow. That's really quick.
Diederichsen: We tried to be rational and that's also why it was cheap. The staff who did the screenings were really good. Around 1 hour for an ordinary patient.
Walton-Shirley: I'm taken aback by the fact that it was free and so cheap, and that it only took an hour. That's remarkable. Many people invited did not participate. Did you analyze only those who were screened?
Diederichsen: It's true. I want to emphasize the difference between the group who attended the screening and the group who did not attend the screening, although they were invited. The attendees were younger, they had fewer comorbidities regarding cardiovascular diseases, and they were taking fewer preventive medications. Those who did not attend were older, on more medication, and so on.
That group, we know, has a higher risk of anything. We did not publish a per-protocol analysis, comparing just those attending vs usual care. We reported the entire group invited vs usual care. You asked me what the event rate was among the ones who attended screening compared to usual care. Remember, the hazard ratio for the entire group was 0.95; for the attendees, it was 0.50.
Walton-Shirley: That's remarkable.
Diederichsen: Yes, but it's not fair to present the per-protocol analysis because we know that there are differences in the attendees vs non-attendees, so there could be other things going on there.
Walton-Shirley: Do you have any ideas or plans for how you're going to entice those who are more socioeconomically disadvantaged to participate in trials and screening?
Diederichsen: We are going to look further into our current data. In Denmark, we can see education, income level, housing. We can see whether you're divorced or single. We can describe our population in Denmark very well and the study participants. We want to analyze whether we managed to recruit and screen those of a lower socioeconomic status or did they did drop out of the study, and if so, why? We'd like to help those below a certain socioeconomic status, because that's where the problem is.
Our next study is with the men aged 60-64 years. We are seeing if there is a difference in participation rate if we send a letter with more words, or would it be better to send a letter with more pictures? We did that in a randomized fashion. I don't know the answer yet. We also sent out a letter saying to please come to a screening explanation on Wednesday at 3 o'clock, and we sent another letter saying, "If you'd like to come to a screening, give us a call."
In DANCAVAS, we told them if you'd like to come to a screening explanation, you're welcome. It was the cleanest way to do it. Now in a second trial, we sent an appointment out, randomized half to Wednesday at 3 o'clock and half to "If you'd like to come, give us a call." Again, we like to look at whether either helps those of lower socioeconomic status come to a screening explanation.
Walton-Shirley: There is a large amount of data here. What kinds of things can we look forward to in your next presentation on this trial?
Diederichsen: I'm looking forward to presenting the data on the age group from 60 to 64 years, in some years from now. In a few months, I hope we can present more about adherence to preventive medication, the attendance rates, and the breakdown by socioeconomic status.
Walton-Shirley: Thank you so much, Dr Diederichsen, for joining us today and for this tremendous body of work that we have to review, thanks to your efforts and those of your team.
Thank you for joining us today on theheart.org | Medscape Cardiology.
Follow theheart.org | Medscape Cardiology on Twitter
© 2022 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: DANCAVAS: Might Cardiovascular Screening Extend Men's Lives? - Medscape - Aug 31, 2022.