Hematomas of at least 5 cm and outcomes in patients undergoing elective percutaneous coronary intervention: Insights from the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial

doi:10.1016/j.ahj.2009.10.034

American Heart Journal

Volume 159, Issue 1, January 2010, Pages 110-116

https://doi.org/10.1016/j.ahj.2009.10.034 Get rights and content

Background

Major bleeding significantly impacts outcomes in patients undergoing percutaneous coronary intervention (PCI). No uniform definitions exist for major and minor bleeding. Hematomas ≥5 cm at the femoral puncture site are considered major bleeding events in some trials and minor in others. Limited information is available on the incidence and clinical relevance of hematomas ≥5 cm in PCI patients.

Methods

Data from the STEEPLE trial in patients undergoing elective PCI were used to assess the impact of hematomas ≥5 cm on ischemic outcomes (mortality, nonfatal myocardial infarction, or urgent target vessel revascularization) up to day 30 and all-cause 1-year mortality. Hematoma data were available for 3,342 of 3,528 patients in STEEPLE. Patients with (n = 103) and without (n = 3,239) hematomas ≥5 cm were evenly distributed across treatment groups.

Results

No differences were observed in 30-day ischemic outcomes between patients with and without hematomas (5.8% vs 5.9%, respectively; P = .96). No transfusions were observed in patients with hematomas as compared with patients without hematomas (0% and 0.4%, respectively; P = .52). A greater reduction in hemoglobin was observed (pre- vs post-PCI) in patients with hematomas as compared with patients without hematomas (−0.84 vs −0.35 g/L, P ≤ .001). No significant difference in all-cause 1-year mortality was observed between patients with and without hematomas (0.0% vs 1.7%, P = .98).

Conclusions

After PCI, hematomas ≥5 cm had no effect on 30-day ischemic events or 1-year mortality. Although there is no agreed classification for large hematomas, the lack of a relationship between hematomas ≥5 cm and clinical outcome after PCI justifies the classification of these hematomas as minor bleeds in STEEPLE.

Section snippets

Methods

The STEEPLE study was an international prospective, open-label, multicenter, randomized, parallel-group trial that has been described in detail previously.¹⁶ Briefly, patients were enrolled if they were ≥17 years of age and scheduled to undergo elective PCI with a femoral approach. Patients were excluded if they met any of the following criteria: recent thrombolysis, a planned stage procedure, increased risk of bleeding, treatment with a parenteral antithrombotic before PCI, or known

Results

A total of 3,528 patients were enrolled in the STEEPLE trial. From this cohort, 3,342 patients had evaluable data on the site and size of puncture site hematomas. Of this group, 103 patients had hematomas ≥5 cm, whereas 3,239 patients had no hematomas ≥5 cm (Figure 1).

Baseline characteristics in patients with and without hematomas ≥5 cm are presented in Table II. Patients with hematomas ≥5 cm were older (P = .003), weighed less (P = .044), and had a decreased incidence of prior unstable angina (

Discussion

The findings of this subanalysis of the STEEPLE trial suggest that the presence of hematomas ≥5 cm had no impact either on a 30-day ischemic composite end point or on all-cause 1-year mortality in patients undergoing PCI in the STEEPLE trial. Patients with hematomas ≥5 cm were more likely to have a significant reduction in their Hb levels post-PCI as compared with pre-PCI levels; however, this was not associated with an increased need for red blood cell transfusions, which was similar in the

Conclusions

The presence of hematomas ≥5 cm had no effect on the 30-day composite ischemic outcome measure or on all-cause 1-year mortality in patients undergoing elective PCI in the STEEPLE trial. Beyond patient discomfort, hematomas ≥5 cm were not associated with an increased need for red blood cell transfusions, although they were associated with a greater reduction in Hb levels after the PCI procedure. It remains to be determined how to use the occurrence of hematomas ≥5 cm in bleeding classifications;

Disclosures

Prof H. White has received research grants from sanofi-aventis, Eli Lilly, The Medicines Company, NIH, Pfizer, Roche, Johnson & Johnson, Schering Plough, Merck Sharpe & Dohme, AstraZeneca, GSK, and Daiichi Sankyo Pharma Development. He has been a consultant for GSK and sanofi-aventis. Dr P. E. Aylward reports receiving grant support from sanofi-aventis, Proctor and Gamble, Alexion, The Medicines Company, Schering Plough, and Eli Lilly, as well as consulting fees and lecture fees from

Acknowledgements

We would like to thank the investigators and patients who took part in this study, and also Barbara Semb for secretarial assistance.

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This study sought to investigate the prognostic value of access site bleeding (ASB) and non-ASB for recurrent ischemic outcomes and mortality in patients with ST-segment elevation myocardial infarction (STEMI).
The prognostic value of ASB-related complications after STEMI is subject to debate.
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Seventy-four patients (3.7%) were treated by radial access. ASB developed in 124 patients (6.3%) and non-ASB developed in 102 (5.2%). By multivariable analysis, ASB was not associated with a higher risk of 1-year mortality (hazard ratio [HR]: 1.03; p = 0.89), recurrent MI (HR: 1.16; p = 0.64), stent thrombosis (HR: 0.55; p = 0.42), or stroke (HR: 0.47; p = 0.31). Non-ASB was independently associated with 1-year mortality (HR: 2.77; p < 0.001) and stent thrombosis (HR: 3.10; p = 0.021), but not with recurrent MI and stroke. In a meta-analysis including 495,630 patients, non-ASB was associated with a greater adjusted risk of subsequent 1-year mortality than ASB (HR: 1.66; 95% CI: 1.56 to 1.76 and HR: 1.21; 95% CI: 1.11 to 1.31).
In STEMI, ASB was not significantly associated with 1-year clinical outcomes, whereas non-ASB was significantly associated with 1-year mortality and stent thrombosis. These results taken together with those of previous studies indicate a greater risk of subsequent mortality in patients with non-ASB.
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This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients.
The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known.
We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model.
A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]).
Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management.
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Bleeding is a major limitation of antithrombotic therapy among invasively managed non–ST-segment elevation acute coronary syndromes (NSTE-ACS) patients; therefore, we examined the use of radial access and its association with outcomes among NSTE-ACS patients.
Clinical characteristics and geographic variation in radial access were examined, as well as its association with bleeding, red blood cell transfusion and ischemic outcomes (96-hour death/myocardial infarction/recurrent ischemic/thrombotic bailout; 30-day death/myocardial infarction; 1-year death) in the EARLY versus delayed, provisional eptifibatide in acute coronary syndromes trial.
Of 9126 patients, 13.5% underwent radial-access catheterization. Female sex, age, weight, and prior revascularization were inversely associated with radial access, and its use varied widely by country (2%-97%). There were fewer GUSTO severe/moderate bleeds and red blood cell transfusions in the radial access group; however, it was attenuated after adjustment (odds ratio 0.73, 95% confidence intervals [CI] [0.50-1.06], P = .094 and 1.00 [0.71-1.40] P = .991). Ischemic outcomes did not differ by access site.
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Citation Excerpt :
However, there was an increase in clinically significant major bleeding using the more sensitive ACUITY scale with cangrelor mainly because of the increased groin hematomas. Groin hematomas have been shown not to be important prognostically,15 and the absolute difference in clinically significant bleeding when groin hematomas were removed was 0.5%. Although prasugrel3 and ticagrelor4 act more quickly than clopidogrel, there remains a need for an intravenous formulation of a P2Y12 inhibitor in patients who cannot tolerate or who may not fully absorb oral drugs such as patients with cardiogenic shock or those who are heavily sedated, nauseated, or vomiting.
There is a clinical need for an intravenous P2Y₁₂ inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y₁₂ inhibitor, bolus 30 μg/Kg plus infusion of 4 μg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies.
As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction.
A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P = .646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P = .037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P = .018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor.
With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non–ST-elevation ACS undergoing PCI.

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Clinical InvestigationInterventional CardiologyHematomas of at least 5 cm and outcomes in patients undergoing elective percutaneous coronary intervention: Insights from the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Conclusions

Disclosures

Acknowledgements

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Cardiovasc Revasc Med

Am J Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention)

Circulation

Circulation

Adverse impact of bleeding on prognosis in patients with acute coronary syndromes

Circulation

Drug insight: bleeding after percutaneous coronary intervention-risks, measures and impact of anticoagulant treatment options

Nat Clin Pract Cardiovasc Med

Clinical Investigation
Interventional Cardiology
Hematomas of at least 5 cm and outcomes in patients undergoing elective percutaneous coronary intervention: Insights from the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial