Bleeding Increases Mortality as Late as 3 Years After DES

Download this article's Factoid (PDF & PPT for Gold Subscribers)

Patients who experience major or minor bleeding after drug-eluting stent (DES) implantation have a heightened mortality risk during both early and late follow-up. In fact, death rates are fully sixfold higher at 3 years in such patients compared with those who have no bleeding, according to a study published in the April 2011, issue of JACC: Cardiovascular Interventions.

The study, led by Seung-Jung Park, MD, PhD, of the Asan Medical Center (Seoul, South Korea), examined the effect of bleeding and MI on 3-year mortality in 3,148 patients who received at least 1 DES for coronary disease between February 2003 and 2006 at 2 centers in South Korea. Bleeding was defined according to STEEPLE major or minor criteria.

Within 3 years of the procedure, bleeding had occurred in 207 patients (6.6%). Most bleeding events (approximately two-thirds) clustered within 30 days of the procedure, although some occurred later, mostly within 1 year. Bleeding was more common in women and older patients as well as those with diabetes, hypertension, prior MI, low LVEF, low hemoglobin, and extensive CAD.

In all, 134 patients died over the 3-year follow-up period, including 71 of cardiac and 63 of noncardiac causes. Eight patients experienced MI after bleeding, and 31 patients died.

Compared with patients who did not have bleeding post-procedure, those who experienced bleeding were at increased risk for death both within 30 days and after 30 days (table 1).

Table 1. Death Rates After DES Implantation

At 3 years, the adjusted risk of mortality was nearly sixfold higher in patients who had bleeding. Post-procedural MI, meanwhile, more than doubled the risk (table 2).

Table 2. Adjusted Mortality Risk Based on MI, Bleeding Events

“Our results indicate that bleeding complications in the early and late periods after DES placement are closely associated with death,” Dr. Park and colleagues conclude. “Therefore, in addition to carefully assessing bleeding complications after stenting, evidence-based medical treatment should be implemented after PCI to offer the best balance between benefit and harm.”

Confirmation of Known Relationship

According to Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), the observation that bleeding is associated with increased mortality is nothing new, and is in fact “very well known.”

Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), said that research groups have been writing about the risks of bleeding for 5 years now, but “there are still people within the medical community that have not gotten the message.”

Methods used to curb bleeding are well studied, Dr. Rao pointed out. In addition to appropriately dosing antithrombotics and adopting newer agents such as bivalirudin and fondaparinux that are associated with lower bleeding risk, physicians should learn and perfect the radial approach, he advised.

“The study does not list how many patients underwent transradial PCI, but 25% of the bleeds in this study were related to the access site, which would be eliminated with the radial approach, and the bulk were non-access site related, which would be minimized with appropriate antithrombotic therapy,” Dr. Rao said.

But Study Comes with Some Twists 

Despite having results that back up years of data linking bleeding to mortality, the study contains some unusual findings, Dr. Brener stressed.

“In all the previous analyses, early MI was associated with a higher mortality than late MI, and in this study it is the opposite,” Dr. Brener said, adding that it was also unusual for bleeding after 30 days to have a greater impact on mortality than earlier bleeding. He suggested that these differences may be the result of the study population.

Dr. Park and colleagues also acknowledge that their results differ from much of the prior literature.

“The mechanisms linking bleeding and subsequent death might be more complicated in the late than in the early period. Prolonged use of dual antiplatelet therapy, consisting of aspirin and clopidogrel, after DES implantation might contribute, at least in part, to the occurrence of bleeding,” they write. “We found that 87% and 34% of our patients remained on dual antiplatelet therapy at 6 months and 1 year, respectively.”

Overall, Dr. Brener said that the association between bleeding and mortality, whether early or late, is generally well known and accepted. What physicians are struggling to understand, he added, is why they are linked.

Although there are hypotheses, the relationship is not easy to document and may or may not be causative, Dr. Brener explained, adding, “Unfortunately, it is not possible to do studies that will determine the link. Instead, all we can do is minimize the risk from bleeding.”

Study Details

Loading doses of 200 mg aspirin and 300 mg clopidogrel were given prior to PCI. After the procedure, patients were advised to adhere to standard dual antiplatelet therapy of 100 mg/day aspirin and 75 mg/day clopidogrel. Clopidogrel was prescribed for a longer period in patients at high risk for ischemic complications.

Kim Y-H, Lee J-Y, Ahn J-M, et al Impact of bleeding on subsequent early and late mortality after drug-eluting stent implantation. J Am Coll Cardiol Intv. 2011;4:423-431.

Related Stories:

• ACUITY: Bivalirudin Lowers Minor Bleeding in SVG PCI Patients
• Causal Relationship Exists Between Bleeding and Mortality