Bleeding in ACS Patients on DAPT Should Prompt Cancer Search

Marlene Busko

August 31, 2019

PARIS — Unexplained bleeding in patients receiving dual antiplatelet therapy (DAPT) after discharge from the hospital for acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) is associated with a fourfold greater likelihood of an imminent cancer diagnosis, a new study suggests.

Isabel Muñoz Pousa, MD, from Hospital Universitario Alvaro Cunqueiro, Vigo, Spain, presented these findings from a large, single-center registry study here at the European Society of Cardiology (ESC) Congress 2019.

The patients with ACS all received DAPT for about a year after they were discharged from the hospital. The "cancers occurring after post-discharge bleeding were mainly located in the genitourinary system (52.1%), in the gastrointestinal tract (20.2%), and in the bronchopulmonary tract (11.7%)," Muñoz Pousa told | Medscape Cardiology in an email.

"Our results suggest that approximately 1 in 10 [cases of] spontaneous bleeding in ACS patients discharged with DAPT is caused by an underlying cancer," she said.

Physicians treating patients with ischemic heart disease need an "increased awareness of the substantially stronger association of spontaneous post-discharge bleeding after ACS with cancer," Muñoz Pousa said.

"A prompt evaluation of bleeding," she stressed, "could be useful for enabling an early detection of cancer, better prognosis, and possibly increased long term survival."

Invited to comment, Matthew T. Roe, MD, Duke Clinical Research Institute, Durham, North Carolina, agreed.

"I think it is a consistent story, where if you are on an antithrombotic regimen — it doesn't necessarily have to be dual antiplatelet therapy — but a regimen where you have bleeding, especially in these areas, that should prompt an evaluation for cancer."

In a patient with a history of ACS who is put on a potent antithrombotic regimen, a bleeding event can lead to further investigation and a "fortuitous" diagnosis of "early-stage cancer that might not have presented for several more years," Roe said.

"Do we believe that these antithrombotic medicines cause cancer?" he asked rhetorically. "No. There is no evidence at all to make the association."

"What I think is that cancer and cardiovascular disease coexist in the elderly population, and they have similar risk factors like smoking or environmental exposure," Roe said. "We need a nimble approach," by oncologists and cardiologists to care for such patients, he added.

"A possible explanation," Muñoz Pousa said in a statement, "is that there is a pre-existing subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack.

"This hypothesis needs to be tested and patients should ensure they take antiplatelets as prescribed to avoid having another heart attack."

Cancer Risk on DAPT

To investigate the association of postdischarge bleeding and new cancer diagnosis, the researchers analyzed data from 3644 patients with ACS who received DAPT after they were discharged from Alvaro Cunqueiro Hospital.  

DAPT was mainly clopidogrel (Plavix, Sanofi) plus aspirin (82.4% of patients), and less often ticagrelor (Brilinta/Brilique, AstraZeneca) or prasugrel (Effient, Lilly/Daiichi Sankyo) plus aspirin, in 11.3% and 6.3% of patients, respectively.

Patients received DAPT for a median of 12.0 months (interquartile range, 6.5 to 14.0 months).

During a median follow-up of 56.2 months, 1215 patients (33%) had a bleeding event, and 227 patients (6%) had a new diagnosis of cancer.  

Of these patients, 827 had a spontaneous bleeding event and 389 had bleeding related to trauma.

Compared to patients with no postdischarge bleeding, those with spontaneous bleeding were much more likely to have a new diagnosis of cancer after multivariable adjustment (hazard ratio [HR], 4.38; P < .001).

But this was not true for patients with bleeding from trauma (HR, 1.29; P = .418).

Genitourinary bleeding (blood in the urine) was linked with an 8.63-fold increased risk for cancer, bronchopulmonary bleeding (coughing up blood) was associated with a 4.26-fold increase in cancer, and gastrointestinal bleeding (blood in the feces) was associated with a 3.78-fold increased risk for cancer (all P =. 001 or less).

Genitourinary, bronchopulmonary, and gastrointestinal bleeding were each associated with site-specific cancers.

Bleeding at other sites was not associated with an increased risk of being diagnosed with cancer.

Most bleeding episodes were mild, but more severe bleeding was more strongly associated with a subsequent cancer diagnosis.

The median time from bleeding to cancer diagnosis was 4.6 months:

The rate of new cancer diagnosis was 15.5 per 100 patients/year in the first 3 months after postdischarge bleeding, 4.0 per 100 patients/year at 3 months to a year after such bleeding, and 1.2 per 100 patients/year at 1 year or longer after such bleeding.

The increased likelihood of being diagnosed with cancer after spontaneous bleeding was the same on DAPT and off DAPT (HR, 3.50 and 3.34, respectively; P < .001 for both).

Bleeding Could "Unmask Cancer"

"I think this poster directly supports the Eikelboom analysis from COMPASS," presented at last year's ESC Congress, Roe said.

John Eikelboom, MD, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada, presented an analysis from the large COMPASS international cohort of patients with stable coronary artery disease or peripheral artery disease who were randomly assigned to rivaroxaban, aspirin, or both. Major gastrointestinal bleeding predicted a large increase in new gastrointestinal cancers, and major genitourinary tract bleeding predicted a large increase in new genitourinary tract cancer. 

In addition to the cardiovascular and mortality benefit of rivaroxaban and aspirin, Eikelboom said in a statement, "If bleeding unmasks cancer it could potentially lead to the added benefit of improved cancer outcomes."

Muñoz Pousa and the other study authors have disclosed no relevant financial relationships. Roe discloses receiving research grant funding from Sanofi-Aventis, Astra Zeneca, Patient Centered Outcomes Research Institute, Ferring Pharmaceuticals, Myokardia, Familial Hypercholesterolemia Foundation, and Bayer and consulting fees or honoraria from Astra Zeneca, Amgen, Cytokinetics, Eli Lilly, Roche-Genentech, Janssen Pharmaceuticals, Regeneron, Novo Nordisk, Pfizer, Sanofi-Aventis, Signal Path, and Elsevier Publishers.  COMPASS was funded by Bayer AG. Eikelboom has received honoraria and/or research support from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Janssen, and Pfizer.

European Society of Cardiology (ESC) Congress 2019. Poster 370. Presented August 31, 2019.

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