Takeshi Kimura

Objective: To assess the long term comparative effectiveness of P2Y12 inhibitor monotherapy compared with aspirin monotherapy in patients after percutaneous coronary intervention (PCI) and discontinuation of dual antiplatelet therapy (DAPT). Methods: Individual participant data (IPD) meta-analysis of randomised clinical trials. Methods: PubMed/Medline, Scopus, Web of Science, and Ovid/Embase. Methods: Randomised trials investigating monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention of ischaemic events in patients with coronary artery disease who underwent PCI. Methods: Anonymised IPD were extracted and transferred to the coordinating centre by dedicated electronic spreadsheets. Data were primarily combined by mixed effects models (one stage analysis) and complemented with multivariable mixed effects models and two stage analyses based on random effects models. The primary and co-primary outcomes were a composite of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding, respectively. The secondary outcomes included a net composite of adverse cardiac and cerebrovascular events (NACCE), derived from the combination of the primary and co-primary outcomes, and individual ischaemic and bleeding events. Results: A total of 16 117 patients assigned to P2Y12 inhibitor or aspirin monotherapy after PCI and completion of the recommended DAPT regimen (median duration of 12 months) in five randomised trials were included. At a median follow-up of 1351 days (interquartile range 373-1791 days), P2Y12 inhibitor monotherapy was associated with a lower risk of MACCE compared with aspirin monotherapy (one stage analysis: hazard ratio 0.77 (95% confidence interval (CI) 0.67 to 0.89), P<0.001; multivariable one stage analysis: adjusted hazard ratio 0.77 (0.67 to 0.89), P<0.001; two stage analysis: hazard ratio 0.77 (0.67 to 0.89), P<0.001), yielding a number needed to treat to benefit of 45.5 (95% CI 31.4 to 93.6). No significant difference in major bleeding (one stage analysis: hazard ratio 1.26 (0.78 to 2.04), P=0.35; multivariable one stage analysis: 1.12 (0.74 to 1.70), P=0.60; two stage analysis: 1.15 (0.69 to 1.92), P=0.59) was observed. NACCE, myocardial infarction, and stroke were lower in patients assigned to a P2Y12 inhibitor compared with those assigned to aspirin. These findings were confirmed across multiple sensitivity and subgroup analyses. Conclusions: In patients who had undergone PCI and discontinued DAPT, at a follow-up of about 5.5 years, P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel was associated with lower MACCE, owing to reduced rates of myocardial infarction and stroke compared with aspirin monotherapy, without a concurrent increased risk of major bleeding.

Background: The prognostic significance of the 6-minute walk distance (6MWD) in patients with severe aortic stenosis (AS) has not been thoroughly investigated. Results: This study evaluated 998 patients with severe AS who underwent a 6-min walk test as part of a large multicenter prospective cohort. Patients were categorized as either fast walkers (6MWD ≥300 m; n=515) or slow walkers (6MWD <300 m; n=483). During a median follow-up of 2.3 years, 861 (86.3%) patients underwent surgical or transcatheter aortic valve replacement (AVR; 87.0% of fast walkers vs. 85.5% of slow walkers). The cumulative 3-year incidence of death was significantly lower among fast walkers than slow walkers (10.9% vs. 31.7%; P<0.001). After adjusting for confounders, slow walkers had a significantly higher risk of all-cause mortality than fast walkers (hazard ratio 2.36; 95% confidence interval 1.55-3.58; P<0.001). Stratified analysis by initial treatment strategy revealed that the cumulative 3-year incidence of all-cause death was consistently lower among fast walkers than slow walkers (initial AVR strategy: 10.1% vs. 28.1% [P<0.001]; conservative strategy: 13.4% vs. 46.7% [P<0.001]). Among asymptomatic patients managed conservatively, fast walkers demonstrated a remarkably low cumulative 3-year incidence of all-cause death (8.1%). Conclusions: The 6MWD is a reliable prognostic marker for patients with severe AS, regardless of initial treatment strategy.

In the article by Yamamoto et al, “Target Lesion Revascularization After Intravascular Ultrasound-Guided Percutaneous Coronary Intervention” which appeared in the May 2023 issue (Circ Cardiovasc Interv. 2023;16:e012922. doi: 10.1161/CIRCINTERVENTIONS.123.012922), corrections were needed. Written informed consent documents were not confirmed by the site monitoring board in 4 patients from 1 participating center in the study population. Based on the suggestion of the central review board (Kyoto University Certified Review Board), these 4 patients should be excluded. The corrections do not impact the interpretations and conclusions of the article.

Unlike patients with acute coronary syndrome (ACS), in whom relatively urgent invasive treatment is favoured, lifestyle guidance and optimal drug treatment are prioritised in patients with chronic coronary syndrome (CCS), and the decision to proceed to coronary revascularisation is more dependent on symptom status and patient preference1. Current guidelines recommend a default antithrombotic strategy of 6-month clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for CCS patients without high bleeding risk; the use of potent P2Y12 inhibitors, such as prasugrel and ticagrelor, is recommended only for patients with high ischaemic risk. Nevertheless, compared with patients with ACS, those with CCS more often have high-risk demographics or clinical features, such as advanced age, multivessel disease, or chronic total occlusion, and complex PCI procedures are often required in CCS patients2. The appropriate antithrombotic management for CCS patients undergoing PCI is still under discussion. The TWILIGHT trial enrolled 7,119 patients with either ACS or CCS, who had trial-defined high-risk features and experienced no significant clinical events during the initial 3-month DAPT following PCI3.

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. 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. 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% vs.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). 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

ShorT and OPtimal Duration of Dual AntiPlatelet Therapy Study After Everolimus-eluting Cobalt-chromium Stent-3

GOREISAN for Heart Failure (GOREISAN-HF) Trial

Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer

ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study

Study to Evaluate the Safety of Reducing Dual Antiplatelet Therapy (DAPT) Duration to 1 Month for Patients With Acute Coronary Syndrome (ACS) After Implantation of Everolimus-eluting Cobalt-chromium Stent