Comprehensive image-based cardiovascular screening in men aged 65-74 years did not significantly reduce all-cause mortality in a new Danish study, although there were strong suggestions of benefit in some cardiovascular endpoints in the whole group and in also mortality in those aged younger than 70.
The DANCAVAS study was presented today at the European Society of Cardiology (ESC) Congress 2022 being held in Barcelona, Spain. It was also simultaneously published online in The New England Journal of Medicine.
“I do believe there is something in this study,” lead investigator Axel Diederichsen, PhD, Odense University Hospital, Odense, Denmark, told theheart.org | Medscape Cardiology.
“We can decrease all-cause mortality by screening in men younger than 70. That’s amazing, I think. And in the entire group the composite endpoint of all-cause mortality/ MI/stroke was significantly reduced by 7%.”
He pointed out that only 63% of the screening group actually attended the tests. “So that 63% had to account for the difference of 100% of the screening group, with an all-cause mortality endpoint. That is very ambitious. But even so, we were very close to meeting the all-cause mortality primary endpoint.”
Diederichsen believes the data could support such cardiovascular screening in men younger than 70. “In Denmark, I think this would be feasible and our study suggests it would be cost effective compared to cancer screening,” he said.
Noting that Denmark has a relatively healthy population with good routine care, he added: “In other countries where it can be more difficult to access care or where cardiovascular health is not so good, such a screening program would probably have a greater effect.”
The population-based DANCAVAS trial randomly assigned 46,611 Danish men aged 65-74 years in a 1:2 ratio to undergo screening (invited group) or not to undergo screening (control group) for subclinical cardiovascular disease.
Screening included non-contrast electrocardiography-gated CT to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation; ankle–brachial blood-pressure measurements to detect peripheral artery disease and hypertension; and a blood sample to detect diabetes and hypercholesterolemia. Of the 16,736 men who were invited to the screening group, 10,471 (62.6%) actually attended for the screening.
In intention-to-treat analyses, after a median follow-up of 5.6 years, the primary endpoint (all cause death) had occurred in 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group (hazard ratio, 0.95; 95% CI, 0.90 – 1.00; P = .06).
The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 – 0.99); for MI 0.91 (95% CI, 0.81 – 1.03); for aortic dissection, 0.95 (95% CI, 0.61 – 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 – 1.35).
The post-hoc composite endpoint of all-cause mortality/stroke/MI was reduced by 7%, with a hazard ratio of 0.93 (95% CI 0.89 – 0.97).
There were no significant between-group differences in safety outcomes.
Subgroup analysis showed that the primary outcome of all-cause mortality was significantly reduced in men invited to screening who were aged 65-69 years (HR, 0.89; 95% CI 0.83 – 0.96), with no effect in men aged 70-74.
Other findings showed that in the group invited to screening there was a large increase in use of antiplatelet medication (HR, 3.12) and in lipid lowering agents (HR, 2.54), but no difference in use of anticoagulants, antihypertensives, and diabetes drugs or in coronary or aortic revascularization.
In terms of cost-effectiveness, the total additional healthcare costs were €207 ($206 US) per person in the invited group, which included the screening, medication, and all physician and hospital visits.
The quality-adjusted life-year (QALY) gained per person was 0.023, with an incremental cost-effectiveness ratio of €9075 ($9043) per QALY in the whole cohort and €3860 ($3846) in the men aged 65-69.
Diederichsen said these figures compared favorably to cancer screening, with breast cancer screening having a cost-effectiveness ratio of €22,000 ($21,923) per QALY.
“This study is a step in the right direction,” Diederichsen told theheart.org | Medscape Cardiology. But governments will have to decide if they want to spend public money on this type of screening. I would like this to happen. We can make a case for it with this data.”
He said the study had also collected some data on younger men — aged 60-64 — and in a small group of women, which has not been analyzed yet. “We would like to look at this to help us formulate recommendations,” he added.
Increased Medical Therapy
Designated discussant of the study at the ESC session, Harriette Van Spall, MD, McMaster University, Hamilton, Canada, congratulated the DANCAVAS investigators for the trial, which she said was “implemented perfectly.”
“This is the kind of trial that is very difficult to run but comes from a big body of research from this remarkable group,” she commented.
Van Spall pointed out that it looked likely that any benefits from the screening approach were brought about by increased use of medical therapy alone (antiplatelet and lipid-lowering drugs). She added that the lack of an active screening comparator group made it unclear whether full CT imaging is more effective than active screening for traditional risk factors or assessment of global cardiovascular risk scores, and there was a missed opportunity to screen for and treat cigarette smoking in the intervention group.
“Aspects of the screening such as a full CT could be considered resource-intensive and not feasible in some healthcare systems. A strength of restricting the abdominal aorta iliac screening to a risk-enriched group — perhaps cigarette smokers — could have conserved additional resources,” she suggested.
Because 37% of the invited group did not attend for screening and at baseline these non-attendees had more comorbidities, this may have caused a bias in the intention to treat analysis toward the control group, thus underestimating the benefit of screening. There is therefore a role for a secondary on-treatment analysis, she noted.
Van Spall also pointed out that because of the population involved in this study, inferences can only be made to Danish men aged 65-74.
Noting that cardiovascular disease is relevant to everyone, accounting for 24% of deaths in Danish females and 25% of deaths in Danish males, she asked the investigators to consider eliminating sex-based eligibility criteria in their next big cardiovascular prevention trial.
Susanna Price, MD, Royal Brompton Hospital, London, UK, and co-chair of the ESC session at which DANCAVAS was presented, described the study as “really interesting” and useful in planning future screening approaches.
“Although the primary endpoint was neutral, and so the results may not change practice at this time, it should promote a look at different predefined endpoints in a larger population, including both men and women, to see what the best screening interventions would be,” she commented to theheart.org | Medscape Cardiology.
“What is interesting is that we are seeing huge amounts of money being spent on acute cardiac patients after having an event, but here we are beginning to shift the focus on how to prevent cardiovascular morbidity and mortality. That is starting to be the trend in cardiovascular medicine.”
Also commenting for theheart.org | Medscape Cardiology, Dipti Itchhaporia, MD, University of California, Irvine, and immediate past president of the American College of Cardiology, said: “This study is asking the important question of whether comprehensive cardiovascular screening is needed, but I don’t think it has fully given the answer, although there did appear to be some benefit in those under 70.”
Itchhaporia questioned whether the 5-year follow up was long enough to show the true benefit of screening, and she suggested that a different approach with a longer monitoring period may have been better to detect AF.
The DANCAVAS study was supported by the Southern Region of Denmark, the Danish Heart Foundation, and the Danish Independent Research Councils.
European Society of Cardiology (ESC) Congress 2022. Presented August 27, 2022.
N Engl J Med. Published online August 27. Full text