Aspirin tablets

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LONDON—Fatal bleeding is rare with extended dual antiplatelet therapy (DAPT), according to research presented at the ESC Congress 2015.

The study included patients with a coronary stent who were receiving 30 months or 12 months of DAPT to prevent stent thrombosis and major cardiovascular and cerebrovascular events.

The results showed that bleeding-related mortality accounted for a minority of deaths in both patient groups.

Laura Mauri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results as abstract 3916. The study, known as the DAPT trial, was funded by a consortium of 8 device and drug manufacturers and other entities.

The trial enrolled patients who were set to receive a drug-eluting or bare-metal stent. After stent placement, they received DAPT—aspirin plus thienopyridine (clopidogrel or prasugrel)—for at least 12 months.

After 12 months of therapy, patients who were treatment-compliant and event-free (no myocardial infarction, stroke, or moderate or severe bleeding) were randomized to continued thienopyridine or placebo, each in addition to aspirin, for an additional 18 months. At month 30, patients discontinued randomized treatment but remained on aspirin for 3 months.

Results from patients with drug-eluting stents were published in NEJM in 2014.

But Dr Mauri reported on causes of death in all 11,648 randomized patients. All deaths were reviewed and adjudicated by an independent committee of cardiologists and oncologists who were blinded to the randomized treatment groups.

Any death that was possibly, probably, or definitely related to any prior clinically evident bleeding event was adjudicated as “bleeding-related,” and any death that was possibly, probably, or definitely related to a malignancy or to complications from treatments specifically administered for the malignancy was adjudicated as “cancer-related.” Fatal bleeding was defined using the Bleeding Academic Research Consortium (BARC) definition.

All-cause mortality

At 30 months (end of the randomization period), the mortality rate was 1.9% in the 30-month treatment group and 1.5% in 12-month group (P=0.07).

There was no significant difference between the groups for cardiovascular mortality—both about 1% (P=0.97)—but there was a significant difference for non-cardiovascular mortality—0.9% and 0.5%, respectively (P=0.01).

At 33 months (combined randomization and aspirin monotherapy periods), the mortality rate was 2.2% in the 30-month treatment group and 1.8% in the 12-month treatment group (P=0.05).

The rates of cardiovascular mortality were 1.2% and 1.1%, respectively (P=0.51). And the rates of non-cardiovascular mortality were 1.0% and 0.7%, respectively (P=0.02).

Bleeding-related deaths

At 33 months, there was no significant difference in bleeding-related mortality. Fatal bleeding occurred in 0.3% of patients in the 30-month group and 0.2% of those in the 12-month group (P=0.36).

There was no significant difference between the groups for bleeding-related death without cancer or trauma (P>0.99), bleeding-related death with cancer (P=0.25), bleeding-related death with trauma (P=0.58), trauma-related death (P=0.30), or trauma-related death without bleeding (P=0.50).

“This analysis of the DAPT study provides valuable insight to suggest that fatal bleeding is rare with extended dual antiplatelet therapy and may be avoided with careful patient selection,” Dr Mauri said.

Cancer-related deaths

Dr Mauri noted that there was no significant difference in the incidence of cancer between the randomized groups (P=0.12). But there was a significant difference in the incidence of cancer-related mortality at 33 months. It was 0.6% in the 30-month group and 0.3% in the 12-month group (P=0.02).

However, when the investigators excluded the cancer-related deaths that occurred in patients whose cancer was diagnosed before they enrolled in the DAPT study, the difference in cancer-related death became non-significant (0.4% and 0.3%, respectively, P=0.16).

“Given the clear benefits of dual antiplatelet therapy in reducing myocardial infarction, these medications remain essential for patients with acute coronary syndromes or coronary stents,” Dr Mauri said. “The relationship with cancer requires further investigation.”

Doc says fatal bleeding with extended DAPT is rare