Hirotoshi Watanabe

Background: There are no studies evaluating mortality and causes of death in severe aortic stenosis (AS) according to symptoms and treatment strategies in contemporary transcatheter aortic valve replacement era. Methods: Among 3369 consecutive patients with severe AS in the CURRENT AS registry-2, we comprehensively evaluated mortality rates and causes of death in patients with severe AS according to symptoms and treatment strategies. Results: There were 2011 patients with symptomatic severe AS [initial aortic valve replacement (AVR) strategy: N = 1410, and conservative strategy: N = 601] and 1358 patients with asymptomatic severe AS (initial AVR strategy: N = 332, and conservative strategy: N = 1026). During median 2.2 years follow-up, all-cause death occurred in 736 patients, including 297 patients with cardiac death (40.4% of total mortality), 44 patients with vascular death (6.0% of total mortality), and 351 patients with non-cardiovascular death (47.7% of total mortality). In patients with cardiac death, the most common cause was heart failure (22.6% of total mortality), and the second most common cause was sudden death (11.7% of total mortality). In patients with non-cardiovascular death, the most common cause was infection (19.3% of total mortality), and the second most common cause was malignancy (12.2% of total mortality). Cumulative 3-year incidence of all-cause death (proportions of cardiac and non-cardiovascular death) was 22.9% (30.2% and 58.2% of total mortality) in symptomatic severe AS with initial AVR strategy, 53.1% (56.1% and 35.6% of total mortality) in symptomatic severe AS with conservative strategy, 15.5% (23.7% and 68.4% of total mortality) in asymptomatic severe AS with initial AVR strategy, and 24.7% (35.7% and 46.9% of total mortality) in asymptomatic severe AS with conservative strategy. Conclusions: There was a great difference in mortality and causes of death according to symptoms and treatment strategies in severe AS. Non-cardiovascular death was one of the major components of death in patients who were managed not only invasively but also conservatively.

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.