Clopidogrel Monotherapy After 1-Month DAPT in Patients With High Bleeding Risk or Complex PCI

BACKGROUND: High bleeding risk (HBR) and complex percutaneous coronary intervention (PCI) are major determinants for dual antiplatelet therapy (DAPT) duration. OBJECTIVES: The aim of this study was to evaluate the effects of HBR and complex PCI on short vs standard DAPT. METHODS: Subgroup analyses were conducted on the basis of Academic Research Consortium-defined HBR and complex PCI in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Verulam's-Eluting Cobalt-Chromium Stent-2) Total Cohort, which randomly compared clopidogrel monotherapy after 1-month DAPT with 12-month DAPT with aspirin and clopidogrel after PCI. The primary endpoint was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (Thrombolysis In Myocardial Infarction [TIMI] major or minor) endpoints at 1 year. RESULTS: Regardless of HBR (n = 1, 893 [31.6%]) and complex PCI (n = 999 [16.7%]), the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (HBR, 5.01% vs 5.14%; non-HBR, 1.90% vs 2.02%; P interaction = 0.95) (complex PCI, 3.15% vs 4.07%; noncomplex PCI, 2.78% vs 2.82%; P interaction = 0.48) and for the cardiovascular endpoint (HBR, 4.35% vs 3.52%; and non-HBR, 1.56% vs 1.22%; P interaction = 0.90) (complex PCI, 2.53% vs 2.52%; noncomplex PCI, 2.38% vs 1.86%; P interaction = 0.53), while it was lower for the bleeding endpoint (HBR, 0.66% vs 2.27%; non-HBR, 0.43% vs 0.85%; P interaction = 0.36) (complex PCI, 0.63% vs 1.75%; noncomplex PCI, 0.48% vs 1.22%; P interaction = 0.90). The absolute difference in the bleeding between 1- and 12-month DAPT was numerically greater in patients with HBR than in those without HBR (-1.61% vs -0.42%). CONCLUSIONS: The effects of 1-month DAPT relative to 12-month DAPT were consistent regardless of HBR and complex PCI. The absolute benefit of 1-month DAPT over 12-month DAPT in reducing major bleeding was numerically greater in patients with HBR than in those without HBR. Complex PCI might not be an appropriate determinant for DAPT durations after PCI. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: From the STOPDAPT-2 Total Cohort

[Background:] The benefit of clopidogrel monotherapy after 1-month dual antiplatelet therapy (DAPT) compared with 12-month DAPT with aspirin and clopidogrel was demonstrated in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), but not in the STOPDAPT-2 acute coronary syndrome (ACS); however, both trials were underpowered based on the actual event rates. [Methods:] We obtained the prespecified pooled population of 5997 patients as the STOPDAPT-2 total cohort (STOPDAPT-2: N=3009/STOPDAPT-2 ACS: N=2988; ACS: N=4136/chronic coronary syndrome [CCS]: N=1861), comprising 2993 patients assigned to 1-month DAPT followed by clopidogrel monotherapy, and 3004 patients assigned to 12-month DAPT with aspirin and clopidogrel after percutaneous coronary intervention. The primary end point was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or any stroke) or bleeding (Thrombolysis in Myocardial Infarction major/minor) end points at 1 year. [Results:] One-month DAPT was noninferior to 12-month DAPT for the primary end point (2.84% versus 3.04%; hazard ratio [HR], 0.94 [95% CI, 0.70–1.27]; Pnoninferiority=0.001; Psuperiority=0.68). There was no significant risk-difference for the cardiovascular end point between the 1- and 12-month DAPT groups (2.40% versus 1.97%; HR, 1.24 [95% CI, 0.88–1.75]; Pnoninferiority=0.14; Psuperiority=0.23). There was a lower risk of the bleeding end point with 1-month DAPT relative to 12-month DAPT (0.50% versus 1.31%; HR, 0.38 [95% CI, 0.21–0.70]; Psuperiority=0.002). One-month DAPT relative to 12-month DAPT was associated with a lower risk for major bleeding regardless of ACS or CCS (ACS: HR, 0.46 [95% CI, 0.23–0.94]; P=0.03, and CCS: HR, 0.26 [95% CI, 0.09–0.79]; P=0.02; Pinteraction=0.40), while it was associated with a numerical increase in cardiovascular events in ACS patients, but not in CCS patients, although not statistically significant and without interaction (ACS: HR, 1.50 [95% CI, 0.99–2.27]; P=0.053, and CCS: HR, 0.74 [95% CI, 0.38–1.45]; P=0.39; Pinteraction=0.08). [Conclusions:] Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT with aspirin and clopidogrel had a benefit in reducing major bleeding events without being associated with increase in cardiovascular events

Disease Modeling of Mitochondrial Cardiomyopathy Using Patient-Specific Induced Pluripotent Stem Cells

Mitochondrial cardiomyopathy (MCM) is characterized as an oxidative phosphorylation disorder of the heart. More than 100 genetic variants in nuclear or mitochondrial DNA have been associated with MCM. However, the underlying molecular mechanisms linking genetic variants to MCM are not fully understood due to the lack of appropriate cellular and animal models. Patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) provide an attractive experimental platform for modeling cardiovascular diseases and predicting drug efficacy to such diseases. Here we introduce the pathological and therapeutic studies of MCM using iPSC-CMs and discuss the questions and latest strategies for research using iPSC-CMs

Clinical Factors of Delayed Perforation after Endoscopic Submucosal Dissection for Gastric Neoplasms

Background. Delayed perforation is a rare but severe complication of endoscopic submucosal dissection (ESD) for early gastric neoplasm (EGN). The aim of this study was to clarify clinical factors related to delayed perforation after ESD. Methods. A total of 1158 consecutive patients with 1199 EGNs underwent ESD at our hospital between January 2000 and December 2015. Univariate analysis was used to identify clinicopathological factors related to delayed perforation. Moreover, duration of cautery needed for hemostasis was measured by comparison between perforated and nonperforated points in patients with delayed perforation. Results. Delayed perforation occurred in 5 of 1158 consecutive patients with 1199 EGNs who underwent ESD (0.42%). All cases were diagnosed within 24 h after ESD and recovered with conservative management. On univariate analysis, location in the upper stomach was the factor most significantly associated with delayed perforation (P<0.01). Duration of cautery needed for hemostasis was significantly longer at perforated points (9 s) than at nonperforated points (3.5 s) in five patients. Conclusions. Location in the upper stomach was the risk factor most prominently associated with delayed perforation after ESD for EGNs. In addition, delayed perforation appears associated with excessive electrocautery for hemostasis

Total and reduced/oxidized forms of coenzyme Q10 in fibroblasts of patients with mitochondrial disease

Coenzyme Q10 (CoQ10) is involved in ATP production through electron transfer in the mitochondrial respiratory chain complex. CoQ10 receives electrons from respiratory chain complex I and II to become the reduced form, and then transfers electrons at complex III to become the oxidized form. The redox state of CoQ10 has been reported to be a marker of the mitochondrial metabolic state, but to our knowledge, no reports have focused on the individual quantification of reduced and oxidized CoQ10 or the ratio of reduced to total CoQ10 (reduced/total CoQ10) in patients with mitochondrial diseases.We measured reduced and oxidized CoQ10 in skin fibroblasts from 24 mitochondrial disease patients, including 5 primary CoQ10 deficiency patients and 10 respiratory chain complex deficiency patients, and determined the reduced/total CoQ10 ratio.In primary CoQ10 deficiency patients, total CoQ10 levels were significantly decreased, however, the reduced/total CoQ10 ratio was not changed. On the other hand, in mitochondrial disease patients other than primary CoQ10 deficiency patients, total CoQ10 levels did not decrease. However, the reduced/total CoQ10 ratio in patients with respiratory chain complex IV and V deficiency was higher in comparison to those with respiratory chain complex I deficiency.Measurement of CoQ10 in fibroblasts proved useful for the diagnosis of primary CoQ10 deficiency. In addition, the reduced/total CoQ10 ratio may reflect the metabolic status of mitochondrial disease

Additional file 1: of A novel scoring system for predicting the neurologic prognosis prior to the initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the CAST score

Comparison of tentative scoring systems created using different algorithms and using different numbers of variables. The logistic regression algorithm yielded a higher sensitivity, specificity, and percentage of correct classification in the cross-validation study, than the decision-tree algorithm (A). The predictive accuracies of three scoring systems created using 6, 8, and 11 variables are shown (P values of 0.001, 0.01, and 0.05, respectively) (B). Logistic logistic regression algorithm, Dec. tree decision-tree algorithm, Se sensitivity, Sp specificity, PCC percentage of correct classification. (TIFF 16702 kb

Additional file 2: of A novel scoring system for predicting the neurologic prognosis prior to the initiation of induced hypothermia in cases of post-cardiac arrest syndrome: the CAST score

Results of external validation of the tentative scoring system. The sensitivity, specificity, and percentage of correct classification for the external validation are shown (A). In these predictive accuracies, the cutoff values for discrimination between a poor and good prognosis was 50% (a “good prognosis” was identified if the probability of a good prognosis on the score was greater than 50%; otherwise, a “poor prognosis” was identified.), 30%, and 15%. The area under the receiver operating characteristic curve of the tentative score for which the logistic regression algorithm was applied with the different cutoff values (B). ROC receive operator characteristic. (TIFF 9281 kb