Background:The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary ...intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001).Conclusions:The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.
Background: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing ...percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1–3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 ≤5 medications 12.5%, T2 6–7 16.5%, and T3 ≥8 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio HR 1.21; 95% confidence interval CI 1.08–1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12–1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 95% CI 0.83–1.09; P=0.47 and HR 1.06 95% CI 0.91–1.23; P=0.48, respectively).Conclusions: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.
There is a scarcity of data on ischemic and bleeding events in patients who experienced major bleeding after percutaneous coronary intervention (PCI). Moreover, there also is a shortage of data on ...comparative outcomes between patients with and without interruption of an antithrombotic drug after major bleeding. We evaluated the incidence and prognostic impacts of ischemic (myocardial infarction or ischemic stroke) and bleeding (Bleeding Academic Research Consortium type 3 or 5) events after major bleeding in 12,691 consecutive patients who underwent first PCI in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI registry cohort-3. In the entire cohort, incidence of the first ischemic event and bleeding event was 2.3 per 100 person-years and 3.8 per 100 person-years, respectively. Major bleeding (Bleeding Academic Research Consortium type 3) occurred in 2,142 patients during a median follow-up of 5.7 years. In patients with major bleeding, cumulative 30-day, 1-year, and 5-year incidence of an ischemic event was 2.6%, 4.8%, and 13.2% (3.2 per 100 person-years), respectively, whereas that of a bleeding event was 6.3%, 16.1%, and 29.2% (8.5 per 100 person-years), respectively. Ischemic and bleeding events were independently associated with mortality (hazard ratio 2.36, 95% confidence interval 1.87 to 2.96, p <0.001, and hazard ratio 2.85, 95% confidence interval 2.42 to 3.37, p <0.001). The cumulative 180-day incidence of ischemic and bleeding events was not significantly different between patients with and without interruption of an antithrombotic drug in patients with major bleeding. In conclusion, the incidence of an ischemic event after the first major bleeding was approximately 1/3 of that of recurrent major bleeding, and the rates of ischemic and bleeding events after the first major bleeding were higher than the rates of first events in the general PCI population. Both ischemic events and bleeding events were strongly associated with subsequent mortality. The incidence of ischemic and recurrent bleeding events was not different between patients with and without interruption of an antithrombotic drug.
Polypharmacy was reported to be associated with increased mortality in various populations. However, there is a scarcity of data on status of polypharmacy and association with long-term mortality in ...patients who underwent percutaneous coronary intervention (PCI). Among 12,291 patients who underwent first PCI in the CREDO-Kyoto PCI/CABG registry Cohort-3, we evaluated the number of medications at discharge from index PCI hospitalization, and compared long-term mortality across the 3 groups divided by the tertiles of the number of medications. The median number of medications was 6 (interquartile range: 5 to 8), and 88.0% of the patients were on >=5 medications. Most of medications were those related to cardiovascular disease. Patients taking more medications were older and more often had co-morbidities and guideline-indicated medications. The cumulative 5-year incidence of all-cause death increased incrementally with increasing number of medications (Tertile 1 <=5: 13.1%, Tertile 2 6 to 7: 13.9%, and Tertile 3 >=8: 18.0%, log-rank p <0.001). After adjusting confounders, the mortality risks of Tertile 2 and Tertile 3 relative to Tertile 1 were no longer significant (Tertile 2: hazard ratio 0.93; 95% confidence interval 0.84 to 1.04; p = 0.23, and Tertile 3: hazard ratio 0.91; 95% confidence interval 0.81 to 1.03; p = 0.14, respectively). In conclusion, in a real-world population of patients who underwent PCI, approximately 90% of patients were on >=5 medications. Increasing medications was associated with higher crude incidence of all-cause death, whereas adjusted mortality risks were similar regardless of the number of medications. These data might suggest that achievement of optimal medical therapy would be preferred, even if it might increase the number of medications used.
The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in “real-world” patients with atrial fibrillation (AF) undergoing ...percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.
ObjectiveTo evaluate changes in demographics, clinical practices and long-term clinical outcomes of patients with ST segment-elevation myocardial infarction (STEMI) before and beyond ...2010.DesignMulticentre retrospective cohort study.SettingThe Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI Registries Wave-1 (2005–2007, 26 centres) and Wave-2 (2011–2013, 22 centres).Participants9001 patients with STEMI who underwent coronary revascularisation (Wave-1: 4278 patients, Wave-2: 4723 patients).Primary and secondary outcome measuresThe primary outcome was all-cause death at 3 years. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, target vessel revascularisation, ischaemia-driven target vessel revascularisation, any coronary revascularisation and any ischaemia-driven coronary revascularisation.ResultsPatients in Wave-2 were older, more often had comorbidities and more often presented with cardiogenic shock than those in Wave-1. Patients in Wave-2 had shorter onset-to-balloon time and door-to-balloon time, were more frequently implanted drug-eluting stents, and received guideline-directed medication than those in Wave-1. The cumulative 3-year incidence of all-cause death was not significantly different between Wave-1 and Wave-2 (15.5% and 15.7%, p=0.77). The adjusted risk of all-cause death in Wave-2 relative to Wave-1 was not significant at 3 years (HR 0.92, 95% CI 0.83 to 1.03, p=0.14), but lower beyond 30 days (HR 0.86, 95% CI 0.75 to 0.98, p=0.03). The adjusted risks of Wave-2 relative to Wave-1 were significantly lower for definite stent thrombosis (HR 0.59, 95% CI 0.43 to 0.81, p=0.001) and for any coronary revascularisation (HR 0.75, 95% CI 0.69 to 0.81, p<0.001), but higher for major bleeding (HR 1.34, 95% CI 1.20 to 1.51, p=0.005).ConclusionsWe could not demonstrate improvement in 3-year mortality risk from Wave-1 to Wave-2, but we found reduction in mortality risk beyond 30 days. We also found risk reduction for definite stent thrombosis and any coronary revascularisation, but an increase in the risk of major bleeding from Wave-1 to Wave-2.
Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event ...after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background :Atorvastatin can inactivate Rho/Rho kinase via a reduction in the synthesis of geranylgeranyl pyrophosphate (GGPP). Thromboxane A2 (TxA2) causes endothelial cell (EC) apoptosis ...via Rho/Rho kinase activation. We tested the hypothesis that atorvastatin protects against the Rho kinase-mediated anti-angiogenic effect of TxA2. Methods : We used human coronary artery ECs to form tubular structures on plates coated with a basement membrane matrix gel. The number of tubular structure was counted under a microscope. The caspase-3 activity was used as a determinant of apoptosis. Results : Atorvastatin significantly increased the number of tubes in a dose-dependent manner, and this effect was blocked by mevalonate or geranylgeranyl pyrophosphate (GGPP). Similar to atorvastatin, a potent selective inhibitor of geranylgeranyl transferase type I enhanced tubular formation. A TxA2 mimetic (IBOP) inhibited formation of EC tubular structures. The inhibitory effect was completely blocked by a TxA2 antagonist (SQ29548), a Rho kinase inhibitor (Y27632), and by atorvastatin. The IBOP-induced increase in caspase-3 activity was attenuated by atorvastatin. Conclusions : Atorvastatin promoted in vitro angiogenesis of ECs in a dose-dependent manner and reversed the TxA2 receptor-mediated anti-angiogenic effect. We suggest that reduction of GGPP and inactivation of Rho kinase plays an important role in the proangiogenic effect of atorvastatin.
One-month duration of dual antiplatelet therapy (DAPT) has widely been adopted after bare-metal stent (BMS) implantation in the real clinical practice. However, it has not been adequately addressed ...yet whether DAPT for only 1-month could provide sufficient protection from ischemic events beyond 1-month after BMS implantation. We assessed the effects of short DAPT relative to prolonged DAPT on clinical outcomes with the landmark analysis at 2 month after BMS implantation. Among 13,058 consecutive patients enrolled in the CREDO-Kyoto registry cohort-2, this study population consisted of 4905 patients treated with BMS only in whom the information on the status of antiplatelet therapy was available at 2 month after stent implantation single-antiplatelet therapy (SAPT) group:
N
= 2575 (acute myocardial infarction (AMI):
N
= 1257, and non-AMI:
N
= 1318), and DAPT group:
N
= 2330 (AMI:
N
= 1304, and non-AMI:
N
= 1026). Cumulative 3-year incidence of the primary outcome measure (a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, and GUSTO moderate/severe bleeding) was not significantly different between the SAPT and DAPT groups (9.8 versus 10.6 %,
P
= 0.34). After adjusting confounders, the risk of SAPT relative to DAPT for the primary outcome measure remained insignificant in the entire cohort (HR 0.97, 95 % CI 0.79–1.19,
P
= 0.77), and in both AMI and non-AMI strata without any significant interaction between clinical presentation (AMI versus non-AMI) and the effect of SAPT relative to DAPT (P interaction = 0.56). In conclusion, short DAPT <2 month after BMS implantation was as safe as prolonged DAPT ≥2-month in both AMI and non-AMI patients.
Abstract Objectives The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily ...clinical practice in Japan. Background The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. Methods In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. Results Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range: 3.1 to 5.2), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). Conclusions No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial ReACT; NCT01123291 )
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