Tsuyoshi Isawa

Background: Data on transcatheter strategies in patients with severe mitral regurgitation (MR) and advanced chronic heart failure requiring Impella support remain limited.Methods and Results: We retrospectively analyzed 33 patients with severe MR and advanced chronic heart failure requiring Impella support, treated with a transcatheter strategy (n=17) or a conservative strategy (n=16). In an overlapweighted Cox model, the transcatheter strategy was associated with a lower in-hospital mortality rate (hazard ratio, 0.13; 95% confidence interval, 0.03–0.52; P=0.004).Conclusions: A transcatheter strategy had survival benefit for this high-risk population.

BACKGROUND: Clopidogrel may have ischemic benefit over aspirin as long-term monotherapy in patients receiving percutaneous coronary intervention. METHODS: Both the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy-2) and STOPDAPT-2 ACS (Short and Optimal Duration of Dual Antiplatelet Therapy-2 Study for the Patients With Acute Coronary Syndrome) were multicenter, open-label, adjudicator-blinded, randomized clinical trials in Japan, with the same protocol except that the STOPDAPT-2 ACS enrolled patients with acute coronary syndrome, exclusively. The patients after percutaneous coronary intervention with cobalt-chromium everolimus-eluting stents were randomized into 1-month dual antiplatelet therapy followed by clopidogrel monotherapy (clopidogrel group) or 12-month dual antiplatelet therapy followed by aspirin monotherapy (aspirin group). Follow-up duration was 5 years. The clinical effect between clopidogrel and aspirin monotherapy was compared by the 1-year landmark analysis in the STOPDAPT-2 ACS and STOPDAPT-2 total cohort, a pooled cohort of the 2 trials. The primary end point was the composite of cardiovascular end point (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) and bleeding end point (Thrombolysis in Myocardial Infarction major/minor). The major secondary end points were each of the cardiovascular composite end point and the bleeding end point. RESULTS: Of 2986 patients (clopidogrel group: 1492, aspirin group: 1494) in the 5-year analysis of the STOPDAPT-2 ACS, 2875 (96.3%) completed follow-up. By the 1-year landmark analysis, clopidogrel group was superior to aspirin group for both the primary end point (6.18% and 8.27%; hazard ratio, 0.75 [95% CI, 0.57–0.997]; P =0.048) and the major secondary cardiovascular end point (4.73% and 6.77%; hazard ratio, 0.70 [95% CI, 0.51–0.96]; P =0.03). In the STOPDAPT-2 total cohort, including 5991 patients, the superiority of clopidogrel over aspirin for the cardiovascular end point was highly significant (hazard ratio, 0.74 [95% CI, 0.60–0.91]; P =0.004), although the superiority on the primary end point was insignificant (hazard ratio, 0.86 [95% CI, 0.72–1.03]; P =0.11). There was no between-groups difference in the major secondary bleeding end point, both in the STOPDAPT-2 ACS and STOPDAPT-2 total cohort. CONCLUSIONS: Clopidogrel monotherapy was superior to aspirin monotherapy for cardiovascular outcomes beyond 1 year after percutaneous coronary intervention, without increased bleeding risk. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02619760 and NCT03462498.

BACKGROUND: There were no previous studies comparing aspirin with clopidogrel on top of oral anticoagulation (OAC) within 1 year after percutaneous coronary intervention when dual therapy with OAC and clopidogrel was recommended. METHODS: We conducted a subgroup analysis stratified by OAC in the 1-year follow-up of the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3), which randomly compared 1-month dual antiplatelet therapy followed by aspirin monotherapy (aspirin group) with 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This subgroup analysis compared aspirin with clopidogrel in patients with or without OAC by the 30-day landmark analysis. The coprimary end points were the cardiovascular (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke), and bleeding end points (Bleeding Academic Research Consortium 3 or 5). RESULTS: In the 30-day landmark analysis (N=5809), there were 788 patients (13.6%) with OAC at discharge. Regardless of OAC, the incidence rates beyond 30 days up to 1 year were similar between the aspirin and clopidogrel groups for cardiovascular end point (OAC: 3.7% versus 3.9%, hazard ratio, 0.92 [95% CI, 0.44–1.93]; no OAC: 3.7% versus 3.6%; hazard ratio, 1.03 [95% CI, 0.77–1.38]; P interaction=0.78) and for bleeding end point (OAC: 3.5% versus 4.2%, hazard ratio, 0.82 [95% CI, 0.39–1.73]; no OAC 1.5% versus 1.4%, hazard ratio, 1.07 [95% CI, 0.66–1.72]; P interaction=0.57). CONCLUSIONS: Aspirin compared with clopidogrel was associated with similar cardiovascular and bleeding outcomes beyond 30 days and up to 1 year after percutaneous coronary intervention regardless of OAC at discharge. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04609111.

BACKGROUND: The effects of the aspirin-free strategy on bleeding and cardiovascular events were unknown in patients with high bleeding risk (HBR), with or without acute coronary syndrome (ACS), undergoing percutaneous coronary intervention. METHODS: We conducted a subgroup analysis stratified by ACS among patients with HBR in the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3), which randomly compared no-aspirin (prasugrel monotherapy) with dual antiplatelet therapy (DAPT) in patients with ACS and HBR. RESULTS: There were 3258 patients with HBR, including 1803 ACS and 1455 non-ACS patients. The effects of no-aspirin compared with DAPT at 1 month after percutaneous coronary intervention were not significant for major bleeding regardless of ACS or non-ACS (7.3% versus 7.9%; hazard ratio [HR], 0.91 [95% CI, 0.65–1.28], and 3.1% versus 2.9%; HR, 1.06 [95% CI, 0.58–1.93]; P interaction=0.66). There was a numerically higher risk in the no-aspirin group relative to the DAPT group for a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke in patients with ACS, but not in patients with non-ACS (7.9% versus 5.8%; HR, 1.39 [95% CI, 0.97–1.99], and 2.4% versus 3.0%; HR, 0.78 [95% CI, 0.41–1.47]; P interaction=0.12). There was a significant treatment-by-subgroup interaction for myocardial infarction (1.6% versus 0.3%; HR, 4.57 [95% CI, 1.31–15.89], and 1.4% versus 1.8%; HR, 0.78 [95% CI, 0.34–1.77]; P interaction=0.02). CONCLUSIONS: The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding in patients with HBR irrespective of ACS. There was a signal of the excess risk of the aspirin-free strategy relative to the DAPT strategy for cardiovascular events, myocardial infarction in particular, in patients with ACS, but not in patients with non-ACS. The aspirin-free strategy may be considered as a potential treatment option after percutaneous coronary intervention in patients with non-ACS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04609111.

Background: Large, diverse cohort studies are essential for determining the incidence and risk factors of major adverse cardiovascular events (MACEs) associated with immune checkpoint inhibitors (ICIs). This study aimed to (1) compare the incidence of MACEs in primary lung cancer patients receiving ICIs versus those receiving non-ICI chemotherapy, and (2) identify risk factors for MACEs in ICI-treated patients. Materials and methods: We performed a retrospective analysis of primary lung cancer patients using a nationwide Japanese database. Patients were stratified by their use of ICIs, and after propensity score matching, outcomes were evaluated over 180 days. Results: The study included 743 propensity-matched patients in each cohort. The median follow-up period was 329 days (interquartile range, 147-625). At 180 days, 4.0% of ICI-treated patients experienced MACEs, significantly higher than those treated with non-ICI chemotherapy (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.07-3.69; P-value = .030). Among MACEs, myocarditis and pericarditis occurred significantly more frequently in patients receiving ICI treatment than in those receiving non-ICI chemotherapy (P-value = .048 for both outcomes). No significant differences were observed in other MACE components. In multivariable analysis, chronic renal failure (HR, 2.16; 95% CI, 1.05-4.46; P-value = 0.038) and prior heart failure (HR, 3.08; 95% CI, 1.86-5.11; P-value < 0.001) were significant risk factors for MACEs. Conclusion: ICI treatment was associated with more frequent MACEs, primarily due to myocarditis and pericarditis. Additionally, prior heart failure and chronic renal failure were key risk factors for MACEs. Clinical trial registration: UMIN000051698

Aims: There were no previous studies comparing aspirin vs. P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). Methods and results: We conducted a pre-specified subgroup analysis based on complex PCI in the 1-year results of the STOPDAPT-3 (ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3) trial, which randomly compared 1-month DAPT followed by aspirin monotherapy (aspirin group) with 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). The main analysis in the present study was the 30-day landmark analysis. The co-primary endpoints were cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding (Bleeding Academic Research Consortium 3 or 5). In the 30-day landmark analysis (N = 5833), there were 1415 patients (24.3%) who underwent complex PCI. There was a significant interaction between complex PCI and the effect of the aspirin group relative to the clopidogrel group for cardiovascular events (complex PCI: 3.3% vs. 5.2%, non-complex PCI: 4.3% vs. 3.6%, interaction P = 0.04) and net adverse clinical events (complex PCI: 4.8% vs. 7.2%, non-complex PCI: 5.3% vs. 4.4%, interaction P = 0.02), but not for bleeding events (complex PCI: 2.1% vs. 2.7%, non-complex PCI: 1.7% vs. 1.4%, interaction P = 0.35). Conclusions: There was a significant interaction between complex PCI and the effect of aspirin monotherapy relative to clopidogrel monotherapy beyond 1 month and up to 1 year for cardiovascular events due to numerically lower risk of aspirin monotherapy in patients with complex PCI, while the effect of aspirin monotherapy relative to clopidogrel monotherapy was not different for bleeding regardless of complex PCI. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown. We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75 mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66–1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69–1.38; P for interaction = 0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78–1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79–1.82; P for interaction = 0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes. The effects of an aspirin-free prasugrel monotherapy (3.75 mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111