JACC: Underlying mechanism is unclear about why post-PCI bleeds lead to death

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Patients with in-hospital major bleeding (IHMB) after primary PCI have significantly increased three-year rates of morbidity and mortality, based on the three-year results of the HORIZONS-AMI trial, published Oct. 17 in the Journal of the American College of Cardiology. However, the researchers and the accompanying  editorialists concluded that further studies should be conducted to understand the underlying mechanism of why this occurs.

Jung-Won Suh, MD, PhD, from the Cardiovascular Research Foundation in New York City, conducted a post-hoc analysis of the three-year results of the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute MI) Trial, which were first presented at TCT.10, to study the effect of IHMB on the long-term prognosis of patients undergoing primary PCI for ST-segment elevation MI (STEMI).

“There is mounting clinical evidence that periprocedural bleeding is an independent predictor of post-procedure adverse outcomes, including death,” wrote the accompanying editorialist Robert J. Applegate, MD, a cardiologist at Wake Forest School of Medicine in Winston-Salem, N.C. “[I]t has been increasingly recognized that the adverse consequences of periprocedural bleeding extends beyond the hospital, for at least as long as six months. Why the impact of periprocedural bleeding should persist beyond the hospitalization and even 30 days is not readily apparent because the effectiveness of most of the antithrombotic therapies would have long worn off.”

In the study, primary PCI was performed in 92.9 percent of 3,602 patients; in-hospital protocol-defined non-CABG-related major bleeding developed in 6.9 percent of patients. The researchers examined medication use at discharge, mortality and major adverse cardiovascular events (composite of death, reinfarction, stroke or ischemic target vessel revascularization) at three-year follow-up in patients with and without IHMB.

Suh and colleagues found that patients with IHMB had higher mortality (24.6 vs. 5.4 percent) and more major adverse cardiovascular events (40.3 vs. 20.5 percent). The deleterious effect of major bleeding was observed within one month, between one month and one year, and between one and three years. IHMB was an independent predictor of mortality at three-year follow-up.

Applegate says that from Suh et al, the cardiology community can learn several things. “First, these data extend the association between in-hospital major bleeding and mortality to three years. Second, this association appears to be independent of use of medications such as aspirin and thienopyridines, although it is unclear what the role of the decreased administration of beta-blocker and statin therapy would have in these events at three years.”

He added that these findings provide “important answers to some of the questions about the mechanisms and duration of the adverse association of bleeding and mortality. However, if the adverse consequences of in-hospital major bleeding are not related to the withdrawal of lifesaving medications (i.e., dual-antiplatelet therapy), then what is the mechanism responsible for increased late mortality in these patients?”

Suh et al also concluded that further investigation is “warranted to understand the mechanisms underlying this relationship and to further improve outcomes in patients with STEMI … and whether the prognosis of these patients may be improved by tailored follow-up and detailed attention to adjunctive pharmacotherapy.”

“Until we have a clearer understanding of the mechanisms of this association, we will need to rely on bleeding avoidance strategies such as gentler antithrombotic pharmacology and access techniques that limit bleeding, to prevent the potentially morbid cascade that seems to follow,” Applegate concluded.