Incidence and Predictors of Vascular Complications after Invasive Coronary Procedures: A Prospective Analysis

Background
Although clinical trial data suggest that the incidence of hemorrhagic and vascular complications associated with invasive coronary procedures is relatively low, contemporary data from ‘real world, non-trial related’data tertiary care centers are lacking. Access site complications are the most common cause of complications following cardiac catheterization procedures. The femoral approach is the most commonly used site of vascular access.¹ Femoral access complication rates are 1.8% for diagnostic and 4% for interventional procedures.³
Even though a number of studies were done to look into such complications, the patients had to meet certain inclusion criteria in order to qualify for participation. Those studies tended to include patients with relatively few comorbidities and a good functional status. Our study includes all patients and, therefore, comes close to what is seen in everyday clinical practice.
An increasing number of interventional procedures, along with intense anticoagulation, increase the need for identifying predictors of complications in order to minimize the risks.

Purpose
The purpose of this study was to determine the incidence and potential predictors of hemorrhagic vascular complications after invasive coronary procedures, either diagnostic alone (contrast angiography [CA]) or combined with an interventional procedure (percutaneous coronary intervention [PCI]) in a tertiary care inner-city urban academic catheterization laboratory.

Methods and Procedures
Study design. The study design was a prospective observational study approved by the Institutional Review Board at our university.
Patient selection. Clinical characteristics and information regarding procedural data were collected for 200 consecutive patients who underwent cardiac catheterization over a period of two months via femoral artery access.
Inclusion criteria. The study included patients undergoing cardiac catheterization for diagnostic or percutaneous intervention.
Exclusion criteria. Those patients who had an access site different from right or left femoral artery, documented coagulation disorders, anticoagulation on warfarin with international normalized ratio (INR) > 2.0 were excluded from the study.
From the procedures using femoral access, there were 124 purely diagnostic and 76 percutaneous coronary interventions. A prospective cohort with femoral access site angiogram was collected and they were observed during the hospital stay.
Complications. Hematoma was defined as a firm collection of blood greater than 2 cm around or in the proximity of the access site. Pseudoaneurysm/dissection, A-V fistula and ischemic leg were also considered, along with retroperitoneal bleed. Retroperitoneal bleeding was defined by any amount of bleeding in the retroperitoneum, diagnosed by computer tomography.

Data Collection Methods and Procedure
Clinical data of all patients who met the criteria were collected and entered into a database. The following agents were used pre-, peri- and post-procedure: aspirin, clopidogrel and heparin. Some patients got eptifibatide, bivalirudin or abciximab in addition to the above. Vascular access sheaths were used in every patient. The artery sheath sizes ranged from 5–8 French (Fr). A modified Seldinger technique was used to cannulate the common femoral artery before the bifurcation. Postprocedure, the artery was sealed either by femoral closure device, stasis patch and Femostop, or manual compression.
All patients undergoing PCI received either 60 U/kg heparin bolus and a glycoprotein (GP) IIb/IIIa inhibitor or bilivarudin. The activated clotting time (ACT) was targeted to be between 250 and 300 seconds. The femoral sheaths were removed immediately after diagnostic procedures. The artery was sealed by a femoral closure device or manual compression. Usually, if the ACT is more than 250, a closure device is used and if it is less than 250, manual compression or a Femostop device is used.
For PCI patients, the sheaths were removed immediately at the end of the procedure if a closure device was used or there was an evidence of expanding hematoma. The femoral sheaths were removed by trained personnel dedicated to the task on a vascular interventional unit or the coronary care unit when the ACT was < 160. The most commonly used closure devices were Angio-Seal (St. Jude Medical, Minnetonka, Minnesota) or Perclose (Abbott Laboratories, Redwood City, California). For mechanical hemostasis, the FemoStop^® (Radi Medical Systems, Uppsala, Sweden) compression device was used. The sealer patch used was Chito-Seal (Abbott). For manual and mechanical hemostasis, the patients were kept on bed rest for 6 hours (hrs). For closure device hemostasis, the patients were kept on bed rest for 2 hours for patients undergoing diagnostic procedures and overnight for patients with PCI procedures.¹
Complications observed. Hematoma not requiring blood transfusion, hematoma requiring blood transfusion, retroperitoneal hematoma, pseudoaneurysm/dissection, A-V fistula, and ischemic leg were the noted complications.
Statistical analysis. The data were analyzed by using SAS V 9.1. A probability value of 0.05 was accepted as the limit of statistical significance. A multivariate logistic regression analysis was used to investigate the association of selected clinical factors (gender, age, body surface area, comorbidities, PCI, fluoroscopy time, type of closure device) to the occurrence of femoral access complications.

Results

Baseline clinical characteristics. Patients with angiographic complications and patients without such events were similar with respect to baseline characteristics, including atherosclerotic risk factors, prior cardiac events, gender, and body mass index (BMI) (Table 1). Patients with and without angiographic complications also had similar medications before coronary intervention, including similar use of aspirin, thienopyridines and heparin. Each gender had 10 individuals with a complication, 9.3% in males and 10.9% in females with no statistical significance (p-value = .81 using a two-sided Fisher’s Exact test).
Procedural characteristics. Angiographic complications were associated with longer procedure durations; median time was 75–130 min for patients with events versus 36–70 min for patients without events (p = 0.001). If the procedure time was 75 minutes or more, there was nearly a 5-fold increase in the possibility of a complication (odds ratio = 4.903, 95% confidence interval [CI] of [1.403, 17.129]) (Figure 1). If the procedure was a PCI, there was nearly a 4-fold increase in the possibility of a complication (odds ratio = 3.885, 95% CI of [1.108, 13.623]). This is by way of logistic regression model. Maximum procedural activated clotting times were similar for patients with and without events.

There were 124 individuals that had a diagnostic catheterization, 4 of whom had complications (3.23%); 76 individuals had PCI, 16 of whom had complications (21.05%), using two-sided Fisher’s exact test, p-value < 0.00011.
The complication rate with a closure device is 7.3% and without a closure device it is 13.2%, but this is not statistically significant (p-value = 0.24 by way of a two-sided Fisher’s exact test).
Eptifibatide and vascular complications. Of 175 individuals not given eptifibatide, 10 had complications (5.71%). Of 25 individuals given eptifibatide, 10 had complications (40%) (two-sided Fisher’s Exact test p < 0.000013).
The logistic regression including eptifibatide was run, which showed that eptifibatide use is highly significant for vascular complications (odds ratio = 5.802, 95% CI of [1.914, 17.590]; p-value = 0.0019).

Discussion
Vascular access complications remain an important cause of catheterization procedure morbidity and mortality.¹ There are a few critical findings of this study. First, eptifibatide use is associated with greater risk of post-procedure bleeding and secondly, the procedure time is one of the predictors of vascular complications. We did not observe complications such as ischemic leg or arteriovenous fistula. This study illustrates that eptifibatide may be associated with more bleeding complications than ischemic complications. Furthermore, comparisons between current cohort results and previous studies are subject to bias, as new technology, medications and improvements in technique should actually decrease the incidence of complications. The higher incidence of bleeding complications in our study compared to prior studies could partially be due to our inclusion of complications occurring even beyond the 24-hr follow-up period and the patient population. On the basis of this observational data, the probability of ischemic complications is low, which may be related to lower levels of anticoagulation as the standard of care in many catheterization laboratories has been the routine administration of a bolus of 10,000 to 15,000 U of heparin to achieve an activated clotting time of at least 300–350 seconds before coronary angioplasty is begun.
Our study concluded that the use of closure devices or Femostop/manual compression did not have any significant impact on the rate of complications, which were consistent with the literature.22 Early ambulation and comfort are important goals of closure devices.
The most frequently used vascular access site for cardiac catheterization is the common femoral artery.^3,21 The common femoral artery is a reasonably large-diameter and superficial vessel, and hemostasis can be obtained by compressing it against the femoral head.
The artery is accessed through anatomic landmarks including the inguinal ligament, radiographic visualization of the femoral head and the direct palpation of the artery.^16,17 An arteriotomy below the distal common femoral bifurcation increases the risk of access site complications due to the inability to compress the artery against the femoral head for hemostasis.^16,17 An arterial puncture above the inguinal ligament accesses the artery in the retroperitoneum. In our patient population, we included only the patients who have arteriotomy below the distal common femoral bifurcation.
The increased association of eptifibatide and complications was evident in data from the ESPRIT trial, but our incidence was much higher, as we included almost all patients undergoing PCI and CA.³

Implications for Practice
There are two implications for clinical practice from this study. First, eptifibatide use, which is a uniform standard of clinical practice for angiographic interventions, is associated with a greater risk of vascular complications. Failure to prevent angiographic complications during coronary intervention may explain morbidity increasing the length of stay. This implies that pharmacologic interventions need to be minimized and used only if their use in absolutely indicated. Secondly, the results of this study support the hypothesis that the greater the procedure time, the greater the risk of vascular complications. Accordingly, the procedure time should be kept as short as possible. The paradox remains that the greatest absolute benefit is achieved among patients in whom the procedure appears to have gone smoothly.

Study Limitations
This study is limited by sample size and from being a prospective observational study. Reliability of the data concerning angiographic complications may be limited since the complications were self-reported by the investigators and not by a core laboratory blinded to treatment. We were unable to control and account for other possible risk factors like severe peripheral vascular disease and other possible risks of arterial site complications, such as multiple punctures of the artery.

Conclusions
Our results show that even with the most recent advances in stent technology, the incidence of vascular complications remains higher with the use of eptifibatide and emphasizes the benefit of keeping the procedure time to a minimum. Our data are unique in showing the reported procedure time to be one of the predictors. Our particular cohort of patients appears to differ substantatively in its outcome compared to published, pivotal studies that draw conclusions for similar populations observed. Because of the limitations (small sample size, observational design, and completion at a single institution), further studies will be necessary to confirm these findings.

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