ABCA1 gene-physical activity interaction for HDL-C

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men

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