Faculty Bibliography

Coronary artery bypass grafting (CABG) is effective in reducing cardiovascular morbidity and mortality in certain high-risk groups. Despite improvement in surgical technique, hemorrhagic complications are a major concern and are likely to affect perioperative morbidity and mortality, length of stay, and hospital expenditures. The use of platelet-directed therapies in this setting is effective in decreasing ischemic complications, yet these agents simultaneously increase the risk of bleeding. Concern about potential hemorrhagic risk from antiplatelet agents in proximity to CABG may influence physicians to discontinue these agents. The benefit of low-dose aspirin given preoperatively is likely to outweigh any hemorrhagic risk. Dual antiplatelet therapy with aspirin and clopidogrel (or aspirin and prasugrel) is associated with a significant increased risk of bleeding and its complications. Additional research is needed to properly evaluate the ischemic benefit versus bleeding risk of aspirin and clopidogrel. Whether reversible P2Y(12) receptor antagonists will mitigate the bleeding risk is unclear at the present time and will require large prospective studies

CONTEXT: Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS). OBJECTIVES: To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates. DESIGN, SETTING, AND PARTICIPANTS: A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina. MAIN OUTCOME MEASURE: Thirty-day mortality following ACS. RESULTS: Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70). CONCLUSIONS: Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease

BACKGROUND: The presence of atherosclerosis in extracardiac vascular beds is associated with an increased risk of adverse cardiovascular outcomes among stable patients with coronary artery disease (CAD). However, there is little data regarding the impact of the presence and extent of vascular disease on outcomes in patients with CAD undergoing percutaneous coronary intervention. METHODS AND RESULTS: We analyzed 69,045 consecutive patients from the New York State Coronary Angioplasty Reporting System database who underwent percutaneous coronary intervention between 1998 and 1999. Vascular disease burden was assessed by history of aortoiliac, femoral-popliteal, and carotid disease. Patients were stratified into 3 groups: CAD alone, CAD and 1 additional site, and CAD and 2 or 3 additional sites. A logistic regression model was constructed to determine the relation between vascular disease burden and in-hospital mortality. Any history of vascular disease was present in 5915 (8.6%) of the population, of whom 4840 (82%) had CAD and 1 other disease location and 1075 (18%) had CAD and 2 or 3 other disease locations. There was a significant relationship between the number of disease locations and hospital mortality, ranging from 0.7% in patients with CAD alone to 2.0% and 2.6% for patients with 1 or >or =2 disease locations, respectively (P<0.001). In unadjusted analysis, in-hospital mortality was approximately 3-fold higher (odds ratio, 2.89; 95% CI, 2.31 to 3.60; P<0.001) and 4-fold higher (odds ratio, 3.78; 95% CI, 2.57 to 5.56; P<0.001) for inpatients with CAD and additional vascular disease at 1 site and > or =2 sites, respectively. After multivariable adjustment, each additional vascular bed affected was associated with a 50% increase in in-hospital mortality (odds ratio, 1.50; 95% CI, 1.27 to 1.78; P<0.001). CONCLUSIONS: Among patients with CAD undergoing percutaneous coronary intervention, vascular disease burden is associated with higher rates of adverse events and is an independent predictor of in-hospital mortality

Platelet-initiated acute thrombosis and coronary embolization are fundamental to the pathophysiology of acute coronary syndromes. Pharmacotherapies aimed at disrupting platelet function via the P2Y(12) receptor have been successful at reducing the incidence of vascular events in randomized clinical trials. However, with the emergence of third and fourth generation drugs, several important considerations remain, including metabolism, timing of onset, variability in platelet response or 'resistance', monitoring ability, and off-target effects. These fundamental properties and distinct profiles may shape the future of cardiovascular therapeutics. Investigation of practical ex vivo platelet performance measurement tools is actively proceeding and may provide important information for patient management

CONTEXT: Randomized trials have shown that aspirin decreases the risk of cardiovascular events in patients with symptomatic coronary and cerebrovascular disease. Despite guideline recommendations for secondary prevention in peripheral artery disease (PAD), the effect of aspirin in this population is not well established. OBJECTIVE: To investigate the effect of aspirin on cardiovascular event rates in patients with PAD. DATA SOURCES AND STUDY SELECTION: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Science Citation Index (1966 to December 2008), and unpublished studies from the supplemental index of the Antithrombotic Trialists' Collaboration. Eligible studies were prospective, randomized controlled trials of aspirin therapy, with or without dipyridamole that reported cardiovascular event rates. Eighteen trials involving 5269 individuals were identified. DATA EXTRACTION: Studies were reviewed to determine the number of participants, mean follow-up, and the primary end point of cardiovascular events (nonfatal myocardial infarction [MI], nonfatal stroke, and cardiovascular death). Data on the secondary end points of all-cause mortality, major bleeding, and the individual components of the primary outcome measure were also abstracted. For the primary end point, the analysis had 88% power to detect a 25% reduction and 70% power to detect a 20% reduction in cardiovascular events in the aspirin group compared with the control group. DATA SYNTHESIS: Among 5269 participants, cardiovascular events were experienced by 251 (8.9%) of 2823 patients taking aspirin (alone or with dipyridamole) and by 269 (11.0%) of 2446 in the control group (pooled relative risk [RR], 0.88; 95% confidence interval [CI], 0.76-1.04). Aspirin therapy was associated with a reduction in the secondary outcome of nonfatal stroke (52 of 2823 vs 76 of 2446; RR, 0.66; 95% CI, 0.47-0.94) but was not associated with significant reductions in all-cause or cardiovascular mortality, MI, or major bleeding. In the subset of 3019 participants taking aspirin alone vs control, aspirin was associated with a nonsignificant reduction in cardiovascular events (125 of 1516 vs 144 of 1503; RR, 0.75; 95% CI, 0.48-1.18), a significant reduction in nonfatal stroke (32 of 1516 vs 51 of 1503; RR, 0.64; 95% CI, 0.42-0.99), but no statistically significant reductions in all-cause or cardiovascular mortality, MI, or major bleeding. CONCLUSIONS: In patients with PAD, treatment with aspirin alone or with dipyridamole resulted in a statistically nonsignificant decrease in the primary end point of cardiovascular events and a significant reduction in nonfatal stroke. Results for the primary end point may reflect limited statistical power. Additional randomized controlled trials of aspirin therapy are needed to establish the net benefit and bleeding risks in PAD

AIMS: Not all patients at risk for sudden cardiac death (SCD) are eligible for, or have access to implantable cardioverter defibrillator (ICD) implantation. There are conflicting data regarding the efficacy and safety of amiodarone for the prevention of SCD. METHODS AND RESULTS: We conducted a meta-analysis of all randomized controlled trials examining the use of amiodarone vs. placebo/control for the prevention of SCD. We identified 15 trials, which randomized 8522 patients to amiodarone or placebo/control. Amiodarone decreased the incidence of SCD [7.1 vs. 9.7%; OR 0.71 (0.61-0.84), P < 0.001] and cardiovascular death (CVD) [14.0 vs. 16.3%; OR 0.82 (0.71-0.94), P = 0.004]. There was a 1.5% absolute risk reduction in all-cause mortality which did not meet statistical significance (P = 0.093). Amiodarone therapy increased the risk of pulmonary [2.9 vs. 1.5%; OR 1.97, (1.27-3.04), P = 0.002], and thyroid [3.6 vs. 0.4%; OR 5.68, (2.94-10.98), P < 0.001] toxicity. CONCLUSION: Amiodarone reduces the risk of SCD by 29% and CVD by 18%, and therefore, represents a viable alternative in patients who are not eligible for or who do not have access to ICD therapy for the prevention of SCD. However, amiodarone therapy is neutral with respect to all-cause mortality and is associated with a two- and five-fold increased risk of pulmonary and thyroid toxicity

BACKGROUND: Despite compelling evidence that aspirin reduces fatal and nonfatal vascular events among the overall population in various settings, women have frequently been underrepresented and their data underreported. We sought to evaluate the relationship between aspirin use, dose (81 or 325 mg), and clinical outcomes among postmenopausal women with stable cardiovascular disease (CVD). METHODS AND RESULTS: Women with CVD (n=8928) enrolled in the Women's Health Initiative Observational Study were used for this analysis. The primary outcome was the incidence of all-cause mortality and cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Among 8928 women with stable CVD, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, aspirin use was associated with a significantly lower all-cause (adjusted hazard ratio, 0.86 [0.75 to 0.99]; P=0.04) and cardiovascular-related mortality (adjusted hazard ratio, 0.75 [0.60 to 0.95]; P=0.01) compared with no aspirin. Aspirin use was associated with a lower risk of cardiovascular events (adjusted hazard ratio, 0.90 [0.78 to 1.04]; P=0.14), which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point. CONCLUSIONS: After multivariate adjustment, aspirin use was associated with significantly lower risk of all-cause mortality, specifically, cardiovascular mortality, among postmenopausal women with stable CVD. No significant difference was noted between 81 mg and 325 mg of aspirin. Overall, aspirin use was low in this cohort of women with stable CVD

Many patients with systolic dysfunction undergo elective percutaneous coronary intervention (PCI) despite the unknown risk and limited data supporting its use. Therefore, the aim of this study was to evaluate the association between the severity of left ventricular (LV) systolic dysfunction and hospital mortality in patients who undergo elective PCI. A retrospective cohort study was conducted of all patients who underwent elective PCI in New York State in 1998 and 1999. Patients were stratified into 5 groups on the basis of their LV ejection fractions (EFs) before PCI (>55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%). Comparisons of demographic, procedural, and outcome variables were performed, and adjusted odds ratios (ORs) were calculated to evaluate the relation between the EF and hospital mortality. Among 55,709 patients who underwent elective PCI, EFs < or =25%, 26% to 35% and 36% to 45% were present in 3.4%, 7.6%, and 17.4%, respectively. Hospital mortality was 0.3%, 0.2%, 0.6%, 1.2%, and 2.7% in the groups with EFs >55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%, respectively (p <0.001). After multivariate adjustment, an increased risk for hospital mortality was significant for EF groups of 36% to 45% (OR 1.56, 95% confidence interval 1.06 to 2.30), 26% to 35% (OR 2.17, 95% confidence interval 1.42 to 3.31), and < or =25% (OR 3.85, 95% confidence interval 2.46 to 6.01) compared with EF >55%, respectively. In conclusion, this analysis demonstrates that elective PCI is commonly performed in patients with reduced EFs, and the risk for hospital mortality increases as the EF decreases. For patients who undergo elective PCI, an EF < or =45% is associated with higher adjusted hospital mortality. Whether elective PCI in patients with low EFs reduces morbidity and/or mortality over medical therapy alone is unknown

OBJECTIVES: The purpose of our multicenter study was to examine the impact of pre-operative administration of clopidogrel on reoperation rates, incidence of life-threatening bleeding, inpatient length of stay, and other bleeding-related outcomes in acute coronary syndrome (ACS) patients requiring cardiopulmonary bypass (coronary artery bypass graft surgery [CABG]) in a broad cross section of U.S. hospitals. BACKGROUND: There is relative uncertainty about the relationship between clopidogrel and CABG-associated outcomes in the setting of ACS. METHODS: A retrospective cohort analysis was performed of randomly selected ACS patients requiring CABG in 14 hospitals across the U.S. Patients exposed to clopidogrel were compared with those not exposed to clopidogrel within 5 days prior to surgery. RESULTS: Of the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 +/- 6.0 days vs. 8.6 +/- 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008). CONCLUSIONS: After ACS, patients who undergo CABG within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding, and increased length of stay. These risks must be balanced by the clinical benefits of clopidogrel use demonstrated in randomized clinical trials