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Background Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second-generation drug-eluting stents, the effects on long-term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second-generation drug-eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%-75%: 2.4-6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1-5 months and 6.3% at 6-9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03-3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88-0.99]), cardiac death (HR, 0.79 [95% CI, 0.70-0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74-0.91]). Results were similar with an index PCI for an acute coronary syndrome. Conclusions Stopping DAPT after 9 months is associated with lower long-term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second-generation drug-eluting stents.

Background Premature discontinuation of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is related to higher short-term risks of adverse outcomes. Whether these risks persist in the long-term is uncertain. Methods and Results We assessed all patients having percutaneous coronary intervention with coronary second- or first-generation drug-eluting stents in the Veterans Affairs healthcare system between 2006 and 2012 who were free of major ischemic or bleeding events in the first 12 months. The characteristics of patients who stopped DAPT prematurely (1-9 months duration), compared with >9 to 12 months, or extended duration (>12 months) were assessed by odds ratios (ORs) from multivariable logistic models. The risk of adverse clinical outcomes over a mean 5.1 years in patients who stopped DAPT prematurely was assessed by hazard ratios (HRs) and 95% CIs from Cox regression models. A total of 14 239 had second-generation drug-eluting stents, and 8583 had first-generation drug-eluting stents. Premature discontinuation of DAPT was more likely in Black patients (OR, 1.54; 95% CI, 1.40-1.68), patients with greater frailty (OR, 1.04; 95% CI, 1.03-1.05), and patients with higher low-density lipoprotein cholesterol, and less likely in patients on statins (OR, 0.87; 95% CI, 0.80-0.95). Patients who stopped DAPT prematurely had higher long-term risks of death (second-generation drug-eluting stents: HR, 1.35; 95% CI, 1.19-1.56), myocardial infarction (second-generation drug-eluting stents: HR, 1.46; 95% CI, 1.22-1.74), and repeated coronary revascularization (second-generation drug-eluting stents: HR, 1.24; 95% CI, 1.08-1.41). Conclusions Patients who stop DAPT prematurely have features that reflect greater frailty, poorer medication use, and other social factors. They continue to have higher risks of major adverse outcomes over the long-term and may require more intensive surveillance many years after percutaneous coronary intervention.

Background: Inflammation is fundamental to the development of atherosclerosis. We examined the effect of anti-inflammatory doses of salicylate on endothelium-dependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects., Methods and Results: We performed a randomized, double-blind, placebo-controlled crossover trial evaluating the effects of 4 weeks of high-dose salsalate (disalicylate) therapy on endothelium-dependent flow-mediated and endothelium-independent vasodilation. Fifty-eight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endothelium-dependent flow-mediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerin-mediated, endothelium-independent vasodilation was unchanged (P=0.97). Endothelium-dependent flow-mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P<0.02) but not in subjects with subtherapeutic levels (P>0.2)., Conclusions: Salsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endothelium-dependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of anti-inflammatory doses of salsalate on cardiovascular risk., Clinical Trial Registration Url: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827.

Background: With adoption of telemedicine, physicians are increasingly asked to diagnose ST-segment elevation myocardial infarctions (STEMIs) based on electrocardiograms (ECGs) with minimal associated clinical information. We sought to determine physicians' diagnostic agreement and accuracy when interpreting potential STEMI ECGs., Methods and Results: A cross-sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, "based on the ECG above, is there a blocked coronary artery present causing a STEMI?" The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty-four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify "true" STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P = 0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty-Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P = 0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P = 0.15)., Conclusions: There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable "stand-alone" diagnostic test.

Background: In acute coronary syndromes, C-reactive protein (CRP) strongly relates to subsequent death, but surprisingly not to recurrent myocardial infarction. Other biomarkers may reflect different processes related to these outcomes. We assessed 8 inflammatory and vascular biomarkers and the risk of death and recurrent nonfatal cardiovascular events in the 16 weeks after an acute coronary syndrome., Methods and Results: We measured blood concentrations of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), soluble intercellular adhesion molecule (ICAM), soluble vascular cell adhesion molecule (VCAM), E-selectin, P-selectin, and tissue plasminogen activator antigen (tPA) 24 to 96 hours after presentation with acute coronary syndrome in 2925 subjects participating in a multicenter study. Biomarkers were related to the risk of death, and recurrent nonfatal acute coronary syndromes (myocardial infarction or unstable angina) over 16 weeks using Cox proportional hazard models. On univariate analyses, baseline CRP (P=0.006), SAA (P=0.012), and IL-6 (P<0.001) were related to death, but not to recurrent nonfatal acute coronary syndromes. VCAM and tPA related to the risk of death (P<0.001, P=0.021, respectively) and to nonfatal acute coronary syndromes (P=0.021, P=0.049, respectively). Adjusting for significant covariates reduced the strength of the associations; however, CRP and SAA continued to relate to death., Conclusions: In acute coronary syndromes, the CRP inflammatory axis relates to the risk of death and may reflect myocardial injury. VCAM and tPA may have greater specificity for processes reflecting inflammation and thrombosis in the epicardial arteries, which determine recurrent coronary events.