Faculty Bibliography

BACKGROUND:Information is limited on contemporary use and outcomes of embolic protection devices (EPDs) in saphenous vein graft interventions. METHODS AND RESULTS/RESULTS:We formed a longitudinal cohort (2005-2009; n=49 325) by linking National Cardiovascular Data Registry CathPCI Registry to Medicare claims to examine the association between EPD use and both procedural and long-term outcomes among seniors (65+ years), adjusting for clinical factors using propensity and instrumental variable methodologies. Prespecified high-risk subgroups included acute coronary syndrome and de novo or graft body lesions. EPDs were used in 21.2% of saphenous vein grafts (median age, 75; 23% women) and were more common in acute coronary syndrome (versus non-acute coronary syndrome; 22% versus 19%), de novo (versus restenotic; 22% versus 14%), and graft body lesions (versus aortic and distal anastomosis; 24% versus 20% versus 8%, respectively). EPDs were associated with a slightly higher incidence of procedural complications, including no reflow (3.9% versus 2.8%; P<0.001), vessel dissection (1.3% versus 1.1%; P=0.05), perforation (0.7% versus 0.4%; P=0.001), and periprocedural myocardial infarction (2.8% versus 1.8%; P<0.001). By 3 years, death, myocardial infarction, and repeat revascularization occurred in 25%, 15%, and 30% of cases, respectively. EPD use was associated with a similar adjusted risk of death (propensity score-matched hazard ratio, 0.96; 95% confidence interval, 0.91-1.02), myocardial infarction (propensity score-matched hazard ratio, 1.00; 95% confidence interval, 0.93-1.09), and repeat revascularization (propensity score-matched hazard ratio, 1.02; 95% confidence interval, 0.96-1.08) in the overall cohort and high-risk subgroups. CONCLUSIONS:In this contemporary cohort, EPDs were used more commonly among patients with high-risk clinical indications, yet there was no evidence of improved acute- or long-term outcomes. Further prospective studies are needed to support routine EPD use.

Randomized clinical trials provide the foundation of clinical evidence to guide physicians in their selection of treatment options. Importantly, randomization is the only reliable method to control for confounding factors when comparing treatment groups. However, randomized trials have limitations, including the increasingly prohibitive costs of conducting adequately powered studies. Local and national regulatory requirements, delays in approval, and unnecessary trial processes have led to increased costs and decreased efficiency. Another limitation is that clinical trials involve selected patients who are treated according to protocols that might not represent real-world practice. A possible solution is registry-based randomized clinical trials. By including a randomization module in a large inclusive clinical registry with unselected consecutive enrolment, the advantages of a prospective randomized trial can be combined with the strengths of a large-scale all-comers clinical registry. We believe that prospective registry-based randomized clinical trials are a powerful tool for conducting studies efficiently and cost-effectively.

BACKGROUND:It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS:We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS/RESULTS:We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION/CONCLUSIONS:In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING/BACKGROUND:The Medicines Company and Terumo.

BACKGROUND:There has been a decline in hospital length of stay (LOS) after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). OBJECTIVES/OBJECTIVE:The objective of this study was to examine whether shorter LOS is safe for older patients undergoing PPCI for STEMI. METHODS:The study analyzed patients' characteristics and 30-day outcomes by LOS (short, ≤3 days; medium, 4 to 5 days; long >5 days; where LOS was the discharge date minus the admission date plus 1) among 33,920 patients with STEMI in the linked CathPCI Registry-Centers for Medicare & Medicaid Services dataset who were ≥65 years of age and treated with PPCI from 2004 to 2009. RESULTS:Percents of patients in each category were as follows: 26.9%, 46.3%, and 26.8% for short, medium, and long LOS, respectively. Patients with a long LOS were generally older, female, and had more comorbidities, including cardiogenic shock and multivessel disease. Patients with a short LOS generally had higher ejection fraction and single-vessel disease. There was no significant difference in 30-day all-cause mortality (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.74 to 1.34) or major adverse cardiac events (MACE) (death, readmission for myocardial infarction, unplanned revascularization: HR: 1.03; 95% CI: 0.86 to 1.25) for medium versus short LOS. There was a significant increase in adjusted mortality (HR: 2.30; 95% CI: 1.72 to 3.07) and MACE (HR: 1.75; 95% CI: 1.44 to 2.12) for long versus short LOS. Patients with a very short LOS (1 to 2 days) had significantly increased 30-day mortality and MACE compared with a 3- to 4-day LOS. CONCLUSIONS:Patients discharged as early as 48 h after PPCI have outcomes similar to patients who stay in the hospital for 4 to 5 days. Early, but not very early (<48 h), discharge may be safe among selected older patients with STEMI.

BACKGROUND:The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. METHODS AND RESULTS/RESULTS:We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2,400,645 patients that underwent PCI were identified. Both non-access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21-5.14) and access site (RR, 1.71; 95% CI, 1.37-2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non-access site-related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. CONCLUSIONS:The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non-access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used.

BACKGROUND:During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS:We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS:The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS:In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

BACKGROUND:Activated clotting time (ACT) is widely used to guide unfractionated heparin dosing during percutaneous coronary intervention. However, its value in predicting complications is controversial in the modern era. We sought to examine the relationship between ACT and outcomes in non-ST-segment-elevation acute coronary syndrome patients. METHODS AND RESULTS/RESULTS:In the Fondaparinux With Unfractionated Heparin During Revascularization in Acute Coronary Syndromes (FUTURA/OASIS-8) trial, 2026 patients with non-ST-segment-elevation acute coronary syndrome treated with fondaparinux 2.5 mg/d and undergoing percutaneous coronary intervention were randomized to low-dose unfractionated heparin (50 U/kg) or standard-dose unfractionated heparin (85 U/kg or 60 U/kg with glycoprotein IIb/IIIa inhibitors, with ACT guidance). No difference was shown for major bleeding and there was a trend toward a reduction in ischemic events with standard-dose unfractionated heparin. To clarify the additional value of ACT guidance, we analyzed with logistic modeling peri-percutaneous coronary intervention outcomes according to peak ACT as a linear function. A threshold effect was then investigated. No linear correlation was found between ACT and thrombotic or bleeding events. In patients not receiving planned glycoprotein IIb/IIIa inhibitors, a significant increase in rates of death, myocardial infarction, and target vessel revascularization was identified in patients with an ACT≤300 s (4.86% versus 2.78%; adjusted odds ratio, 1.84; 95% confidence interval, 1.06-3.21; P=0.03). No threshold was found for hemorrhagic complications in patients with or without glycoprotein IIb/IIIa inhibitors. CONCLUSIONS:Non-ST-segment-elevation acute coronary syndrome patients undergoing percutaneous coronary intervention with an ACT≤300 s are at increased risk of thrombotic complications. ACT, however, does not predict hemorrhagic complications. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790907.

OBJECTIVES/OBJECTIVE:The purpose of this study was to determine the efficacy and safety of radial versus femoral access in women undergoing coronary angiography/intervention. BACKGROUND:The risk of bleeding and vascular access site complications are higher in women than in men. METHODS:In a pre-specified RIVAL (RadIal Vs femorAL access for coronary intervention) subgroup analysis, we compared outcomes in women (n=1,861) and men (n=5,160) randomized to radial versus femoral access. RESULTS:Overall, women were at higher risk of major vascular complications compared with men (4.7% vs. 1.7%; p<0.0001). Major vascular complications were significantly reduced with radial access in women (3.1% vs. 6.1%; hazard ratio [HR]: 0.5; 95% confidence interval [CI]: 0.32 to 0.78; p=0.002) and in men (0.7% vs. 2.8%; HR: 0.27; 95% CI: 0.17 to 0.45; p<0.0001; interaction p=0.092). Crossover rates were higher with radial compared with femoral access in women (11.1% vs. 1.9%; HR: 5.88; p<0.0001) and men (6.3% vs. 1.9%; HR: 3.32; p<0.0001; interaction p=0.054). Percutaneous coronary intervention (PCI) success rates were similar irrespective of access site (women: HR: 1.05; p=0.471; men: HR: 1.00; p=0.888; interaction p=0.674), with no differences in PCI complications. In multivariable analyses, female sex was an independent predictor of major vascular complications (HR: 2.39; 95% CI: 1.76 to 3.25; p<0.0001). There were consistent findings for women and men, with no difference for the primary composite endpoint of death, myocardial infarction, stroke, and non-coronary artery bypass grafting bleeding (women: 3.9% vs. 5.0%; HR: 0.77; 95% CI: 0.50 to 1.19; men: 3.54% vs. 3.5%; HR: 1.00; 95% CI: 0.75 to -1.34; interaction p=0.325). CONCLUSIONS:Women undergoing coronary angiography and PCI have a higher risk of vascular access site complications compared with men, and radial access is an effective method to reduce these complications.