Non-Access Site Bleeds After PCI More Dangerous Than Access Site Bleeds

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Non-access site bleeds are much more closely tied to 1-year mortality and stent thrombosis in patients after primary percutaneous coronary intervention (PCI) than access site bleeds, according to a single-center patient review and a meta-analysis published as a single paper online May 14, 2014, ahead of print in JACC: Cardiovascular Interventions.

Researchers led by Jose P.S. Henriques, MD, PhD, of Academic Medical Center-University of Amsterdam (Amsterdam, the Netherlands),  compared rates and prognostic significance of access site and non-access site bleeding in 2,002 STEMI patients undergoing primary PCI at his institution between January 2003 and 2008. In addition, a meta-analysis of 5 studies including almost 5,000 patients who underwent PCI for various indications was performed to assess the same comparison.

One-year mortality was 11.8% in patients included in the analysis and 10.3% in excluded patients. Seventy-four patients (3.54%) underwent PCI via radial access, while 1,910 (95.4%) received femoral access, and the remaining 16 (0.8%) received a combination of femoral and radial access or an access site other than femoral or radial.

Overall, 9.9% of patients experienced GUSTO severe or moderate bleeding within 30 days. Of these, 52% had non-access site bleeding, and 63.2% experienced bleeding originating at an arterial puncture site (30 patients experienced both).

On Kaplan-Meier analysis, 1-year mortality was 41.2% in patients with non-access site bleeding and 25.8% in those with access site bleeding. On multivariable adjustment, non-access site bleeding was associated with roughly threefold higher all-cause death, cardiac death, and stent thrombosis at 1 year compared with access-site bleeding (table 1).

Table 1. Adjusted 1-Year Outcomes: Non-Access Site vs Access Site Bleeding


HR (95% CI)

P Value

All-Cause Death


< .001

Cardiac Death


< .001

Stent Thrombosis

3.10 (1.19-8.11)


Roughly 9% of patients with non-access site bleeding discontinued clopidogrel vs about 2% of patients with access site bleeding (P = .019). Rates were about 16% vs 5%, respectively, for discontinuation of either aspirin or clopidogrel (P =.006).

The location of bleeding events ranged from large groin hematoma (28.1%) to GI (20.4%) to “other arterial puncture site” (21.4%) to intracranial (0.5%).

In the meta-analysis of 495,630 patients, both access-site-related and non-access-site-related bleeding were associated with 1-year mortality. However, the degree of risk depended on the source of bleeding; the adjusted risk of 1-year mortality was higher in patients with non-access site-related bleeding compared with patients with access site bleeding (combined hazard ratios of 1.66 and 1.21, respectively).

Why Outcomes Are Worse for Non-Access Site Bleeding

The authors cite a number of factors that may contribute to the difference in prognostic value  between access site and non-access site bleeding. The latter:

  • More often leads to discontinuation of antithrombotic therapy, which is known to increase the risk of stent thrombosis and recurrent MI
  • Occurs in anatomically more remote areas of the body, resulting in a greater delay between bleeding onset and diagnosis; such bleeds are also less accessible by interventions
  • May unveil previously concealed ominous comorbidities, such as malignancy
  • May be a marker of unmeasured confounders or frailty

“Our study supports the need to develop treatment strategies that diminish [non-access site bleeding],” Dr. Henriques and colleagues conclude.

In an email with TCTMD, Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), noted that the findings “confirm the results of prior studies and demonstrate that while bleeding at both sites is associated with an increase in adverse outcomes, the non-access site bleeds are probably worse.”

He added that the results are in accordance with what is generally seen at the bedside. “Access site bleeds are caused by the arterial puncture (ie, iatrogenic), while non-access site bleeds come from lesions that were likely there prior to the cath and thus are part of the patient’s underlying risk,” Dr. Rao said. “For example, a gastric or duodenal ulcer that ends up bleeding due to anticoagulation is likely going to result in much worse outcomes.”

Be Alert to Noncardiac Problems

The key, he said, is to try to gain an understanding of any noncardiac morbidities and review all laboratory values prior to taking the patient to the cath lab. “Anemia,” he continued, “even if mild, can indicate an underlying slow, subclinical bleeding process. Of course, in emergency situations this is not possible, so it is important to dose antithrombotic drugs appropriately and use targeted anticoagulants (like bivalirudin) when indicated.”

Overall, Dr. Rao stressed, “It is important to prevent both access site and non-access site bleeding events. A two-pronged strategy including use of radial access and appropriate pharmacology is best,” he concluded

Note: Coauthors George B. Dangas, MD, PhD, and Roxana Mehran, MD, both of Mount Sinai Medical Center (New York, NY), are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.


Kikkert WJ, Delewi R, Ouweneel DM, et al. Prognostic value of access site and non-access site bleeding after percutaneous coronary intervention: a cohort study in ST-segment elevation myocardial infarction and comprehensive meta-analysis. J Am Coll Cardiol Intv. 2014; Epub ahead of print.



  • The study was supported by the Nuts OHRA Foundation.
  • Drs. Henriques and Rao report no relevant conflicts of interest.


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