Mass Cardiovascular Testing May Add Years for Some Men

BARCELONA -- In Denmark, population-based screening for subclinical cardiovascular disease (CVD) did not prevent deaths in men except perhaps those younger than age 70, a randomized trial found.

Among men ages 65-74, those invited to comprehensive screening, and those not invited, shared statistically similar rates of all-cause death over a median 5.6 years (12.6% vs 13.1%, HR 0.95, 95% CI 0.90-1.00) on intention-to-treat analysis of the DANCAVAS trial.

However, there was an interaction by age, such that deaths were reduced in those invited for screening at ages 65-69 (HR 0.89, 95% CI 0.83-0.96) but not at ages 70-74 (HR 1.01, 95% CI 0.94-1.09), reported Axel Diederichsen, PhD, of Odense University Hospital at the European Society of Cardiology (ESC) meeting. The results were simultaneously published in the New England Journal of Medicine.

"I'm not saying you go out there and screen every man over 60. I don't think we're here yet," Diederichsen cautioned at a ESC press conference, but "if it works in Denmark, it might work in other countries as well."

The investigators had hoped that broad screening would reduce potentially preventable CV events in residents of select municipalities in Denmark participating in this trial.

A previous Danish study, the Viborg Vascular trial, found a 7% reduction in all-cause mortality at 5 years following a combined screening program for abdominal aortic aneurysm, peripheral artery disease, and hypertension in older men.

Diederichsen's group suggested that the more promising results in younger DANCAVAS participants may be related to their greater likelihood of benefiting from screening, given their lesser known history of CVD and lower baseline use of preventive medications and more smoking compared with older peers.

On that 11% relative reduction in deaths in the younger cohort, Diederichsen noted that "this is a never-before-seen reduction in a community-based screening trial."

Nevertheless, this subgroup analysis was not adjusted for multiple testing and will need to be confirmed in a future study. The ongoing DANCAVAS II study is recruiting Danish men, ages 60-64, and will also address socioeconomic factors in cardiovascular prevention.

DANCAVAS was a randomized trial of all men, ages 65-74, living in select regions of Denmark. Over 45,000 men were randomized and split between those invited to screening or left unaware of the program.

Screening included noncontrast electrocardiography-gated CT to determine coronary artery calcium, ankle-brachial blood-pressure measurements, and blood sampling for diabetes and cholesterol levels. According to Diederichsen, 62.6% of the invited group ultimately underwent screening,

Across those invited and not invited, and screened and unscreened, over half of participants were already on antihypertensives, over a third on lipid-lowering agents, and over a quarter on antiplatelets before randomization.

Even so, the DANCAVAS screening was associated with improved rates of all-cause mortality, stroke, or heart attack (HR 0.93, 95% CI 0.89-0.97) on post hoc analysis of the entire cohort. There appeared to be a reduction in stroke (HR 0.93, 95% CI 0.86-0.99) alone as an individual outcome but not others such as myocardial infarction, aortic dissection, or aortic rupture.

The safety of screening was supported by a lack of excess cancers. However, there was a nonsignificant trend toward more severe bleeding (6.8% vs 6.3%, P=0.06) in line with the higher use of antiplatelets among the screened group.

"Recent evidence suggests that antiplatelet agents are ineffective in primary prevention in older persons and those with asymptomatic peripheral artery disease, and thus they would no longer be considered to be indicated in many participants to whom they were prescribed in this trial," the authors noted.

Separately, they performed a cost-effectiveness analysis suggesting the CVD screening to cost an estimated 9,075€ (about $9,000) per quality-adjusted life year (QALY) across DANCAVAS participants, dropping down to 3,860€ per QALY for men ages 65-69.

The mechanism of benefit is likely mediated by medical therapy alone, as screened men increased their uptake of antiplatelet and lipid-lowering drugs without undergoing more coronary and aortic revascularization procedures, commented ESC session discussant Harriette Van Spall, MD, MPH, of the Population Health Research Institute at McMaster University in Hamilton, Ontario, Canada.

She noted that it remains unknown whether comprehensive CVD screening would help women -- not included in the study because of low expected event rates -- or people outside Denmark.

"Aspects of the intervention could be considered resource-intensive and not feasible in some healthcare systems," she said.

"The benefit of screening would be expected to vary depending on access to care and to the extent of use of appropriate preventive treatment in routine primary care," Diederichsen's group agreed.

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