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Exp Clin Cardiol. 2010 Fall; 15(3): e57–e60.
PMCID: PMC2954030
Clinical Cardiology: Original Article

Bleeding complications associated with glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older undergoing percutaneous coronary intervention

Abstract

BACKGROUND:

Treatment of symptomatic coronary artery disease with percutaneous intervention requires antithrombotic therapy. Patients with elevated thromboembolic risk benefit from therapy with glycoprotein IIb/IIIa inhibitors. The safety and effectiveness of glycoprotein IIb/IIIa inhibition have been well documented in clinical trials. Drug-induced bleeding complications in elderly patients have not been specifically addressed.

METHODS:

Between 2006 and 2009, a total of 439 unselected patients 80 years of age and older undergoing percutaneous intervention for symptomatic coronary artery disease were included in the present nonrandomized retrospective study. In one-half of the patients, glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The in-hospital occurrence of bleeding complications (access site, gastrointestinal and cerebral) were analyzed in the groups with and without glycoprotein IIb/IIIa inhibitors.

RESULTS:

The mean age of the patients was 84 years. Nearly all patients (95%) received dual antiplatelet therapy. Patients treated with glycoprotein IIb/IIIa inhibitors had more complex coronary lesions and bypass graft interventions, and a tendency toward more access site bleeding complications than patients without inhibitors, which included femoral hematomas (4.6% versus 2.3%, respectively; P not significant) and femoral pseudoaneurysms (6% versus 3.2%, respectively; P not significant). The rate of blood transfusion was equal in both groups (0.9%). Major hemorrhagic events did not occur. Vessel closure devices were used more often in patients without glycoprotein inhibition.

CONCLUSIONS:

An increase in minor bleedings must be expected when using glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older. However, this issue must not prevent this treatment option from being offered to elderly patients. There appears to be no elevated risk for major bleeding complications. Broadened use of vascular closure devices in this specific patient population may lower the rate of access site complications.

Keywords: Bleeding complications, Glycoprotein IIb/IIIa inhibitors, Octogenarians, Percutaneous coronary intervention

Percutaneous coronary intervention is a common therapy for patients with symptomatic coronary artery disease. Standard pharmacological regimens during percutaneous coronary intervention include acetylsalicylic acid, thienopyridines and heparin. Glycoprotein IIb/IIIa inhibitors have been shown to reduce ischemic complications associated with coronary angioplasty in patients with elevated risk (1). This aggressive antithrombotic and rheological therapy is associated with an increased risk of bleeding complications (14). Other than access site bleeding complications, gastrointestinal, cerebral and pulmonary hemorrhages have been reported. However, the majority of bleeding complications occur at the vascular access site (5,6). The safety and efficacy of glycoprotein IIb/IIIa inhibition has been well documented in clinical trials. A meta-analysis of 21 randomized trials (1) with glycoprotein IIb/IIIa inhibitors revealed a major bleeding rate of 4.23%. However, octogenarians were excluded in most reports.

Several risk factors for bleeding complications have been identified (715). Hemorrhagic events have been reported, especially in elderly patients (4). With the increasing age of the population, cardiovascular diseases are becoming a greater health burden. Coronary artery disease is a major cause of morbidity and mortality, and acute myocardial infarction is associated with particularly high mortality in elderly patients (16). Due to increased life expectancy, a rising number of percutaneous coronary interventions with optional treatment with glycoprotein inhibitors must be expected in elderly patients.

Scarce data are available on the frequency and relevance of bleeding complications in octogenarians undergoing percutaneous coronary intervention with glycoprotein IIb/IIIa receptor inhibition. The aim of the present study was to evaluate the frequency and clinical relevance of bleeding complications associated with glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in patients 80 years of age and older.

METHODS

A total of 439 unselected patients 80 years of age and older were consecutively included in the present retrospective analysis. All patients underwent percutaneous coronary intervention for symptomatic coronary artery disease. In 218 patients (50%), glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The in-hospital occurrence of bleeding complications (access site, gastrointestinal and cerebral bleeding) were compared in the groups treated with and without glycoprotein IIb/IIIa inhibitors. Patients were assessed clinically, and in the case of access site complications, colour duplex sonography was performed.

In all patients, percutaneous coronary interventions were performed by femoral arterial access applying the Judkins technique using 6 Fr sheaths. In the majority of patients, sheaths were removed 2 h after the end of the interventional procedure, followed by mechanical compression with the FemoStop device (Radi Medical Systems, Sweden) for an additional 2 h. Finally, pressure banding was applied for 24 h. In other patients, the Angio-Seal closure device (St Jude Medical Inc, USA) was applied immediately after the interventional procedure.

Standard medication during interventional procedures included 5000 IU of heparin and 500 mg acetylsalicylic acid intravenously. Thienopyridines were given peri-interventionally if they were not administered before the intervention. Glycoprotein IIb/IIIa inhibitors were given during intervention at the interventionalist’s discretion. Standard dosages were used (tirofiban 0.4 μg/kg/min for 30 min followed by 0.1 μg/kg/min for 24 h; abciximab 0.25 μg/kg bolus followed by 0.125 μg/kg/min for 24 h; eptifibatide 180 μg/kg bolus followed by 2 μg/kg/min for 24 h).

RESULTS

A total of 439 patients 80 years of age and older were consecutively included in the present study (mean [± SD] age 84±3 years) (Table 1). All patients underwent percutaneous coronary intervention for symptomatic coronary artery disease. In 218 patients (50%), glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The following inhibitors were used: tirofiban (78.9%), abciximab (11.5%) and eptifibatide (9.6%). In the group with glycoprotein inhibitors, more patients had a history of coronary artery bypass graft surgery (27.4% versus 14.9%, respectively) and significantly more patients had acute coronary syndrome compared with the group without inhibitors (45.4% versus 25.8%, respectively). Coronary stenoses were more complex in patients with inhibitors, more coronary vessel recanalizations were performed (21.4% versus 5%, respectively) and venous bypass grafts were more often the target vessel for intervention (15.6% versus 3.6%, respectively) (Table 2).

TABLE 1
Patient baseline characteristics
TABLE 2
Angiographic data

Vascular closure devices were inserted more often in patients without glycoprotein inhibitors (33.0%) versus patients with glycoprotein inhibitors (19.3%). Manual compression and pressure banding were used in the majority of patients in both groups.

During hospitalization, no cerebral or gastrointestinal bleeding complications occurred. Compared with the group without glycoprotein inhibitors, more access site bleeding complications, including femoral hematomas (4.6% versus 2.3%, respectively) and femoral pseudoaneurysms (6.0% versus 3.2%, respectively), were documented in patients treated with inhibitors. Management of complications did not differ significantly between the groups (Table 3).

TABLE 3
Peri-interventional bleeding complications

DISCUSSION

Large trials investigated the safety of the glycoprotein inhibitor abciximab (6,1719). In the Evaluation in PTCA to improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) trial (18), major hemorrhagic complications occurred in 2% to 3.1% of patients receiving abciximab. Bleeding rates lower than 10% were documented in the Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II (IMPACT II) study (20) of eptifibatide, whereas the Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis (RESTORE) (21) and Platelet Receptor inhibition in Ischaemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS) (22) trials showed major bleeding after administration of tirofiban of 2.4% and 4.0%, respectively. There is likely no significant difference in the rate of bleeding complications between the different glycoprotein IIb/IIIa inhibitors (23). A meta-analysis (1) summarized the rate of major bleeding events as 4.23%. However, these data did not focus on elderly patients. Combining four large studies (6,1719), the use of abciximab was not associated with an increase in major bleeding events across different age groups (4). Nevertheless, the number of patients older than 70 years of age was very limited.

The general risk of bleeding events is elevated when using an aggressive antithrombotic and rheological therapy (2,3). Additional risk factors are peripheral arterial disease, elevated age, female sex, localization of puncture, thickness of sheath and renal insufficiency (7,13,14,2426).

In our patients, who were 80 years of age and older, administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention was associated with a slightly increased rate of access site complications. However, this difference was not statistically significant. The necessity of blood transfusion was rare (0.9%) and equal in patients with and without glycoprotein inhibitors. Pseudoaneurysms were managed similarly by manual compression or injection of thrombin. A surgical procedure was not necessary. Gastrointestinal or cerebral bleeding complications did not occur in either group. Our findings of minor bleeding complications in elderly patients are even lower than those reported in the literature. Use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in this specific patient population is safe.

Within our study population, vascular closure devices were used differently in patients treated with and without glycoprotein IIb/IIIa inhibitors. Closure devices were inserted significantly more often in patients treated without inhibitors. This may contribute to the slightly increased rate of minor access site complications in patients treated with glycoprotein inhibitors. Consequently, in elderly patients treated with inhibitors peri-interventionally, a vascular closure device should be used whenever possible. However, as a limiting factor of our study, time of sheath removal could have influenced the rate of local bleeding complications. Removal guided by activated clotting time could increase its safety. Nevertheless, there was no difference in removal procedure between the study groups.

Management of patients with coronary artery disease and coronary syndromes should be based on evaluation of individual mortality risk. In the setting of an increased risk, the option of peri-interventional glycoprotein IIb/IIIa inhibitor therapy should be considered. This also applies to patients 80 years of age and older. The potential treatment benefit would surpass the slightly increased risk for minor access site bleeding complications.

There is clear evidence supporting the clinical benefits of glycoprotein IIb/IIIa inhibitor treatment in percutaneous coronary intervention in patients with acute coronary syndrome. The initial drawback of hemorrhagic complications was overcome by the use of vascular closure devices. An increase in minor bleeding must be expected when using glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older. However, this must not prevent this treatment option from being offered to elderly patients. There seems to be no elevated risk for major bleeding complications. Broadened use of vascular closure devices in this specific patient population may lower the rate of access site complications.

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