Kai Nyman

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 In the IAC group, warfarin was withdrawn for a mean of 3 days prior to PCI (mean INR 1.7).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.

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.

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.

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.

CHADS2, CHA2DS2-VASc and HAS-BLED as predictors of outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention

INTRODUCTION CHADS2 and CHA2DS2-VASc scores are used to estimate thromboembolic risk in atrial fibrillation (AF). HAS-BLED is recommended for bleeding risk prediction. Their value in predicting the outcome of AF patients after percutaneous coronary intervention (PCI) is unknown. Thus, our aim was to assess whether these simple risk scores are useful in predicting outcome in these patients. MATERIALS AND METHODS AFCAS is an observational, multicenter, prospective registry including patients (n=929) with AF referred for PCI. Primary study endpoints were 1) all cause mortality; 2) major adverse events (all-cause mortality, myocardial infarction, repeat revascularization, stent thrombosis, transient ischemic attack, stroke or other arterial thromboembolism; MACCE); and 3) bleeding at 12 months follow-up. CHADS2 and CHA2DS2-VASc scores and a modified HAS-BLED (mHAS-BLED) score (omitting labile INR and liver function) were calculated. RESULTS Patients were distributed as follows: CHADS2 low 29.5%, intermediate 55.2%, high 15.3%; CHA2DS2-VASc low 9.6%, intermediate 46.0%, high 44.5%. A high CHA2DS2-VASc score was predictive of all-cause mortality (p=0.02), whereas CHADS2 was not. High CHA2DS2-VASc score predicted MACCE (HR 2.24, 95%CI 1.21-4.17, p=0.01), as did a high CHADS2 score (HR 1.60, 95%CI 1.05-2.45, p=0.029). Their predictive performance was only modest (C indexes 0.56-0.57). CHADS2 or CHA2DS2-VASc scores were not associated with bleeding. High mHAS-BLED scores (≥3) were not associated with any of the study outcomes. CONCLUSIONS High CHA2DS2-VASc score was the best predictor of thrombotic outcomes after PCI in a high risk AF population. High mHAS-BLED score was not predictive of bleeding events. More accurate, simple risk scores are needed.

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.

Early Neointimal Coverage and Vasodilator Response Following Biodegradable Polymer Sirolimus-Eluting vs. Durable Polymer Zotarolimus-Eluting Stents in Patients With Acute Coronary Syndrome

BACKGROUND Patients at high bleeding risk would benefit from a shorter dual antiplatelet therapy after PCI. Compared to first-generation devices, the design of newer generation drug-eluting stents may facilitate more rapid anatomical and functional healing of stented vessel based on thinner stent platforms, biodegradable/biocompatible polymers and rapid drug elution. METHODS AND RESULTS Forty-four non-diabetic patients with acute coronary syndrome (ACS) and culprit lesion in the LAD were randomized to receive either biodegradable polymer sirolimus-eluting stent (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES). Neointimal strut coverage was examined using optical coherence tomography, and vasodilator response on invasive thermodilution-derived coronary flow reserve (CFR) at 3-month follow-up. The primary endpoints were percent uncovered struts and CFR. A total of 425 cross-sections (4,897 struts) were analyzed in the BP-SES group, and 425 cross-sections (5,467 struts) in the DP-ZES group. The percent uncovered struts was lower in the BP-SES group compared with the DP-ZES group, both at strut level (3.9% vs. 8.9%, respectively, P<0.001), and stent level (3.9 ± 3.2% vs. 8.9 ± 6.9%, respectively, P=0.019). No significant difference was found between the 2 groups regarding CFR (3.0 ± 1.3 vs. 3.2 ± 1.0, respectively, P>0.05). CONCLUSIONS In non-diabetic patients with ACS, BP-SES provided slightly better stent strut coverage at 3 months compared with DP-ZES, but neither stent was fully covered. No difference in vasodilator response was seen.

Impact of anaemia on clinical outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry

Objectives Anaemia has an adverse impact on the outcome in the general patient population undergoing percutaneous coronary intervention (PCI). The aim of this study was to analyse the impact of anaemia on the 12-month clinical outcome of patients with atrial fibrillation (AF) undergoing PCI and therefore requiring intense antithrombotic treatment. We hypothesised that anaemia might be associated with a worse outcome and more bleeding in these anticoagulated patients. Setting Data were collected from 17 secondary care centres in Europe. Participants Consecutive patients with AF undergoing PCI were enrolled in the prospective, multicenter AFCAS (Atrial Fibrillation undergoing Coronary Artery Stenting) registry. Altogether, 929 patients participated in the study. Preprocedural haemoglobin concentration was available for 861 (92.7%; 30% women). The only exclusion criteria were inability or unwillingness to give informed consent. Anaemia was defined as a haemoglobin concentration of <12 g/dL for women and <13 g/dL for men. Outcome measures The primary endpoint was occurrence of major adverse cardiac and cerebrovascular events (MACCE) or bleeding events. Results 258/861 (30%) patients had anaemia. Anaemic patients were older, more often had diabetes, higher CHA2DS2-VASc scores, prior history of heart failure, chronic renal impairment and acute coronary syndrome. Anaemic patients had more MACCE than non-anaemic (29.1% vs 19.4%, respectively, p=0.002), and minor bleeding events (7.0% vs 3.3%, respectively, p=0.028), with a trend towards more total bleeding events (25.2% vs 21.7%, respectively, p=0.059). No difference was observed in antithrombotic regimens at discharge. In multivariate analysis, anaemia was an independent predictor of all-cause mortality at 12-month follow-up (hazard ratio 1.62, 95% CI 1.05 to 2.51, p=0.029). Conclusions Anaemia was a frequent finding in patients with AF referred for PCI. Anaemic patients had a higher all-cause mortality, more thrombotic events and minor bleeding events. Anaemia seems to be an identification of patients at risk for cardiovascular events and death. Trial registration ClinicalTrials.gov number NCT00596570.

Gender-based analysis of randomized comparison of bioactive versus everolimus-eluting stents in acute coronary syndrome.

Aims The randomized comparison of titanium-nitride-oxide-coated bioactive stent with everolimus-eluting stent in acute coronary syndrome (BASE-ACS) trial demonstrated an outcome of the titanium-nitride-oxide coated bioactive stents (BASs) that was statistically noninferior to that of the everolimus-eluting stents (EESs) at 12-month follow-up, in patients presenting with acute coronary syndrome (ACS) who underwent early percutaneous coronary intervention. We performed a post-hoc gender-based analysis of the BASE-ACS trial at 24-month follow-up. Methods A total of 827 patients (198 women) with ACS were randomly assigned to receive either BAS or EES. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. Results Women were older, and more likely to have diabetes and hypertension compared with men (P < 0.05 for all). Moreover, women had significantly smaller reference vessel diameter and stent diameter (P < 0.05 for all). At 24-month follow-up, the cumulative incidence of the primary endpoint was similar between the two sex subgroups (15.2 versus 11.0%, for women versus men, respectively, P = 0.13). However, the rate of nonfatal MI was significantly higher in women compared with men (8.6 versus 3.8%, respectively, P = 0.007). After propensity score-adjusted analysis, there was a trend toward more nonfatal MI among women (8.6 versus 4.0%, respectively, P = 0.08). Moreover, among male patients, those assigned to BAS had significantly lower nonfatal MI compared with those assigned to EES (P = 0.027). However, among patients assigned to EES, female patients had a significantly higher rate of nonfatal MI compared with men (P = 0.02). Conclusion In the current post-hoc gender-based analysis of the BASE-ACS trial, the 24-month outcome of patients undergoing percutaneous coronary intervention for ACS was slightly worse in women, compared with men, as reflected by a trend toward more nonfatal MI events after propensity score-adjusted analysis.