Pasi P. Karjalainen

Safety of percutaneous coronary intervention during uninterrupted oral anticoagulant treatment

AIMS Uninterrupted anticoagulation (UAC) is assumed to increase bleeding and access-site complications. A common consensus is to postpone percutaneous coronary interventions (PCI) to reach international normalized ratio (INR) levels < 1.5-1.8. METHODS AND RESULTS To assess the safety and feasibility of UAC, we analysed retrospectively all consecutive patients (n = 523) on warfarin therapy referred for PCI in four centres with a policy to interrupt anticoagulation (IAC) before PCI and in three centres with a long experience on UAC during PCI. Major bleeding, access-site complications, and major adverse cardiac events (death, myocardial infarction, target vessel revascularization, and stent thrombosis) were recorded during hospitalization. In the IAC group, warfarin was withdrawn for a mean of 3 days prior to PCI (mean INR 1.7). In the UAC group, mean INR value was 2.2. Glycoprotein IIb/IIIa (GP) inhibitors (P < 0.001) and low-molecular-weight heparins (P < 0.001) were more often used in the IAC group. Major bleeding and access-site complications were more common in the IAC group (5.0% vs. 1.2%, P = 0.02 and 11.3% vs. 5.0%, P = 0.01, respectively) than in the UAC group. After adjusting for propensity score, the group difference in access-site complications remained significant [OR (odds ratio) 2.8, 95% CI (confidence interval) 1.3-6.1, P = 0.008], but did not remain significant in major bleeding (OR 3.9, 95% CI 1.0-15.3, P = 0.05). In multivariable analysis, femoral access (OR 9.9, 95% CI 1.3-75.2), use of access-site closure devices (OR 2.1, 95% CI 1.1-4.0), low-molecular-weight heparin (OR 2.7, 95% CI 1.1-6.7) and old age predicted access-site complications, and the use of GP inhibitors (OR 3.0, 95% CI 1.0-9.1) remained as a predictor of major bleeding. CONCLUSION Our study shows that PCI is a safe procedure during UAC with no excess bleeding complications.

One‐Year Outcome of Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting: An Analysis of the AFCAS Registry

Most evidence regarding the efficacy and safety of the antithrombotic regimens for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention with stent (PCI‐S) derives from small, single‐center, retrospective datasets. To obtain further data on this issue, we carried out the prospective, multicenter, observational Management of patients with Atrial Fibrillation undergoing Coronary Artery Stenting (AFCAS) registry (Clinicaltrials.gov identifier NCT00596570).

Safety of Diagnostic Coronary Angiography During Uninterrupted Therapeutic Warfarin Treatment

Long-term warfarin therapy is assumed to increase bleeding and access site complications after coronary angiography and it is often recommended to postpone invasive procedures to reach international normalized ratio (INR) levels <1.8. To assess the safety and feasibility of diagnostic coronary angiography during uninterrupted warfarin therapy, we retrospectively analyzed all consecutive patients (n = 258) on warfarin therapy referred for diagnostic coronary angiography in 2 centers with long experience in uninterrupted warfarin therapy during coronary angiography and in 1 center with a policy of preprocedural warfarin pause. An age- and gender-matched control group (n = 258) with similar disease presentation (unstable or stable symptoms) was collected from each center. Radial access was used in 56% of patients in the warfarin group and in 60% of controls (p = 0.21). There was no difference in access site and bleeding complications (1.9% vs 1.6%) or major adverse cardiovascular and cerebrovascular events (0.4% vs 0.8%) between the warfarin group and their controls. Warfarin was interrupted in 80 patients (31%), and bridging therapy was used in 24 of these patients (30%). INR levels were higher in the uninterrupted warfarin group (2.3 vs 1.9, p <0.001), but the incidence of access site complications was not higher (1.7%) than in patients (n = 80) with a warfarin pause (2.5%) or in patients with pause and bridging therapy (8.3%). Need for blood transfusions (n = 2) occurred only in patients with bridging therapy. Access site complications were more common in the 22 patients with supratherapeutic anticoagulation (INR >3) than in patients with therapeutic periprocedural INR (9.1% vs 1.5%, p <0.05). In conclusion, a simple strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation is a tempting alternative to bridging therapy and is likely to lead to considerable cost savings.

Bacterial Signatures in Thrombus Aspirates of Patients With Myocardial Infarction

Background— Infectious agents, especially bacteria and their components originating from the oral cavity or respiratory tract, have been suggested to contribute to inflammation in the coronary plaque, leading to rupture and the subsequent development of coronary thrombus. We aimed to measure bacterial DNA in thrombus aspirates of patients with ST-segment–elevation myocardial infarction and to check for a possible association between bacteria findings and oral pathology in the same cohort. Methods and Results— Thrombus aspirates and arterial blood from patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (n=101; 76% male; mean age, 63.3 years) were analyzed with real-time quantitative polymerase chain reaction with specific primers and probes to detect bacterial DNA from several oral species and Chlamydia pneumoniae. The median value for the total amount of bacterial DNA in thrombi was 16 times higher than that found in their blood samples. Bacterial DNA typical for endodontic infection, mainly oral viridans streptococci, was measured in 78.2% of thrombi, and periodontal pathogens were measured in 34.7%. Bacteria-like structures were detected by transmission electron microscopy in all 9 thrombus samples analyzed; whole bacteria were detected in 3 of 9 cases. Monocyte/macrophage markers for bacteria recognition (CD14) and inflammation (CD68) were detected in thrombi (8 of 8) by immunohistochemistry. Among the subgroup of 30 patients with myocardial infarction examined by panoramic tomography, a significant association between the presence of periapical abscesses and oral viridans streptococci DNA–positive thrombi was found (odds ratio, 13.2; 95% confidence interval, 2.11–82.5; P=0.004). Conclusions— Dental infection and oral bacteria, especially viridans streptococci, may be associated with the development of acute coronary thrombosis.

A prospective randomised comparison of titanium-nitride- oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS trial

AIMS Titanium-nitride-oxide-coated bioactive stents (BAS) have demonstrated a favourable outcome when compared with paclitaxel-eluting stents in patients with acute myocardial infarction (MI). In a prospective randomised non-inferiority study design, we compared the safety and efficacy of BAS versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). METHODS AND RESULTS We randomised 827 patients with ACS (1:1) to either BAS (417) or EES (410). The primary endpoint was a composite of cardiac death, non-fatal MI or ischaemia-driven target lesion revascularisation (TLR) at 12-month follow-up. Analyses were performed by intention to treat. At 12-month follow-up, the primary composite endpoint occurred in 9.6% of patients in the BAS group and 9.0% of those in the EES group (HR [hazard ratio] 1.04, 95% CI [confidence interval] 0.81-1.32, p=0.81, p for non-inferiority =0.001). Non-fatal MI was significantly less frequent in the BAS as compared with the EES group (2.2% vs. 5.9%, p=0.007). However, the individual rates of cardiac death and ischaemia-driven TLR were similar between the two groups (1.9% vs. 1.0%, p=0.39, and 6.5% vs. 4.9%, p=0.37, respectively). CONCLUSIONS In patients presenting with ACS, BAS achieved a clinical outcome that was non-inferior to EES at 12-month follow-up.

Titanium-nitride-oxide coated stents versus paclitaxel-eluting stents in acute myocardial infarction: a 12-months follow-up report from the TITAX AMI trial.

AIMS The aim of this study was to evaluate the effectiveness of titanium-nitride-oxide (TITANOX)-coated stent and paclitaxel-eluting stent (PES) in patients presenting with acute myocardial infarction (MI). METHODS AND RESULTS A total of 425 patients presenting with acute non-ST-elevation MI or ST-elevation MI were randomly assigned to receive TITANOX-coated stent or PES. The primary end point was a composite of MI, target lesion revascularisation (TLR) or death from cardiac causes. At 12 months, there was no significant difference between patients receiving TITANOX-coated stent or PES in the rates of primary end point (10.3% vs. 12.8%, P=0.5), MI (4.2% vs. 8.1%, P=0.1), or TLR (9.3% vs. 7.1%, P=0.5), respectively. The incidence of stent thrombosis, defined according to Academic Research Consortium classification, was significantly lower in the TITANOX group compared to the PES group (0.9% vs. 4.3%, P=0.03). CONCLUSIONS TITANOX-coated stent and PES resulted in comparable clinical outcomes during 12 months follow-up among patients treated for acute MI.

Five-year clinical outcome of titanium-nitride-oxide-coated bioactive stent implantation in a real-world population: a comparison with paclitaxel-eluting stents: the PORI registry.

AIMS We sought to present the 5-year clinical outcome of the titanium-nitride-oxide-coated bioactive stents (BAS), as compared to paclitaxel-eluting stents (PES), in a real-world patient population. METHODS From May 2003 to November 2004, we enrolled 405 consecutive patients who underwent percutaneous coronary intervention with either BAS or PES implantation. Patients were prospectively followed up for 5 years. The primary end-point was major adverse cardiac events (MACE) at 5-year follow-up including cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization. RESULTS A total of 201 patients received BAS (218 lesions/221 stents) while 204 patients received PES (244 lesions/247 stents). Clinical follow-up for 5 years was completed in all patients. Cumulative MACE at the end of 5-year follow-up occurred in 34 (16.9%) patients in the BAS group, as compared to 53 (26%) in the PES group (OR 1.7, 95% CI 1.1-2.8, P = 0.03). This difference was mainly driven by a lower incidence of MI in the BAS group as compared with the PES group (9.5% vs. 20.6%, OR 2.5, 95% CI 1.4-4.4, P = 0.002). Stent thrombosis occurred in 16 (7.8%) patients in the PES group, while no one suffered stent thrombosis in the BAS group. CONCLUSION BAS implantation in a real-world patient population achieves an excellent clinical outcome over 5-year follow-up, with a significantly lower incidence of MI, MACE, and stent thrombosis as compared to PES.

Two-year follow-up after percutaneous coronary intervention with titanium-nitride-oxide-coated stents versus paclitaxel-eluting stents in acute myocardial infarction

Background and aims. The aim of this study was to evaluate the long-term effects of the titanium-nitride-oxide-coated (TITANOX) stent and the paclitaxel-eluting stent (PES) in patients who had undergone a percutaneous coronary intervention for acute myocardial infarction (MI). Methods and results. The TITAX-AMI trial randomly assigned 425 patients with MI to receive either a TITANOX stent or a PES. The primary end-point was a composite of MI, target lesion revascularization, or death from cardiac causes. At 12 months, there was no significant difference between patients receiving TITANOX stent or PES in the rate of primary end-point (10.3% versus 12.8%, P=0.5). After 2 years of follow-up, a significantly lower rate of primary end-point was observed in the TITANOX stent group compared with the PES group (11.2% versus 21.8%, HR 2.2, 95% confidence interval (CI) 1.3–3.8, P=0.004). This difference was driven by a reduced rate of MI (5.1% versus 15.6%, P<0.001) and cardiac death (0.9% versus 4.7%, P=0.02) in favour of the TITANOX stent. Definite stent thrombosis occurred in 0.5% and 6.2% of the patients (P=0.001), respectively. Conclusions. The implantation of a TITANOX stent resulted in better clinical outcome compared with a PES during 2 years of follow-up among patients treated for acute MI.

Five-year clinical outcome of titanium-nitride-oxide-coated bioactive stents versus paclitaxel-eluting stents in patients with acute myocardial infarction: Long-term follow-up from the TITAX AMI trial

BACKGROUND The TITAX-AMI randomized controlled trial demonstrated a better clinical outcome with titanium-nitride-oxide-coated bioactive stents (BAS) as compared with paclitaxel-eluting stents (PES) at 2-year follow-up, in patients with acute myocardial infarction (MI) undergoing early percutaneous coronary intervention (PCI). We sought to present the 5-year clinical outcome of the TITAX-AMI trial. METHODS A total of 425 patients with acute MI were randomly assigned to receive either BAS (214), or PES (211). The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, recurrent MI or ischemia-driven target lesion revascularization (TLR). Clinical follow-up was performed to 5 years. RESULTS The 5-year cumulative incidence of MACE was significantly lower in patients assigned to BAS as compared with those assigned to PES (16.4% versus 25.1%, respectively, p=0.03). Similarly, the 5-year rates of cardiac death and recurrent MI were significantly lower in patients assigned to BAS (1.9% versus 5.7%, and 8.4% versus 18.0%, p=0.04 and p=0.004, respectively). Yet, the rates of ischemia-driven TLR were similar between the two study groups (11.2% versus 10.9%, respectively, p=0.92). The rate of definite stent thrombosis (ST) was again significantly lower in patients assigned to BAS (0.9% versus 7.1%, respectively, p=0.001). CONCLUSIONS In the current prospective randomized TITAX-AMI trial, among patients presenting with acute MI who underwent early PCI, BAS achieved a better clinical outcome as compared with PES at 5-year follow-up, as reflected by lower cumulative rates of overall MACE, cardiac death, recurrent MI, and definite ST; yet, with statistically similar rates of ischemia-driven TLR.

Are glycoprotein inhibitors safe during percutaneous coronary intervention in patients on chronic warfarin treatment

The aim of this study was to evaluate the safety of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients on chronic warfarin therapy due to atrial fibrillation (AF). We analysed all consecutive AF patients (N = 377, mean age 70 years, male 71%) on warfarin therapy referred for PCI in seven centres. Major bleeding, access site complications and major adverse cardiovascular events were recorded during hospitalisation. A total of 111 patients (29%) received periprocedural GPIs with a wide inter-hospital variation in their use (range 3-68%). The use of GPIs increased with the severity of the disease presentation and 49% of patients with ST-elevation myocardial infarction received GPIs. Mean periprocedural international normalised ratio (INR) of patients who received GPIs was 1.89 (range 1.1-3.3). Major bleeding was more common in the patients treated with GPIs (9.0% vs. 1.5%, p = 0.001) than in those without GPIs, but there was no difference in major adverse cardiovascular events between the groups. In multivariable analysis, use of GPIs (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.3-20.6, p = 0.02) and old age (OR 1.2, 95% CI 1.0-1.3, p= 0.02) remained as the only independent predictors of major bleeding. Also after adjusting for propensity score, GPIs remained as a significant predictor of major bleeding (OR 3.8, 95% CI 1.03-14.1, p = 0.045). In the GPI group, major bleeding was not predicted by INR level or warfarin pause. GPIs increase the risk of major bleeding events irrespective of periprocedural INR levels and should be used with caution in this fragile patient group.