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The aim of this study was to assess the impact of age on the safety and efficacy of ticagrelor monotherapy after percutaneous coronary intervention (PCI). As the risk for bleeding and ischemic complications after PCI increases with age, the authors conducted a pre-specified analysis of the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial to evaluate the possible benefits of ticagrelor monotherapy according to age. The TWILIGHT trial enrolled patients undergoing PCI with drug-eluting stents who fulfilled at least 1 clinical and 1 angiographic high-risk criterion. Age ≥65 years was a clinical entry criterion. After 3 months of dual-antiplatelet therapy with ticagrelor, event-free patients were randomized to ticagrelor plus placebo or ticagrelor plus aspirin for an additional 12 months. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding. The key secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke. A total of 3,113 patients (47.7%) were ≥65 years of age. At 1 year after randomization, ticagrelor monotherapy significantly reduced BARC type 2, 3, or 5 bleeding (4.5% vs. 8.2%; hazard ratio: 0.53; 95% confidence interval: 0.40 to 0.71) without increasing ischemic events (4.2% vs. 4.4%; hazard ratio: 0.96; 95% confidence interval: 0.68 to 1.35) compared with ticagrelor plus aspirin among patients ≥65 years of age. These findings were consistent in patients <65 years of age with respect to the primary (p interaction = 0.62) and key secondary (p interaction = 0.77) endpoints and across different age categories. A strategy of ticagrelor monotherapy following 3 months of dual-antiplatelet therapy significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin without an increase in ischemic events, irrespective of age. [Display omitted] [ABSTRACT FROM AUTHOR]

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y 12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y 12 -inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention–treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention. • Different P2Y 12 inhibitors have enabled physicians to contemplate individualized treatment regimens. • In selective scenarios, PFT and genotyping may be used as optional tools for guiding treatment. • Further studies on DAPT de-escalation and escalation are needed to refine existing treatment options. [ABSTRACT FROM AUTHOR]

Background: Length of stay after non-ST-segment elevation myocardial infarction (NSTEMI) continues to decrease, but information to guide duration of hospitalization is limited.Methods: We used landmark analyses, in which the landmark defined potential days of discharge, to estimate complication rates on the first day the patient would have been out of the hospital, and estimated associations between timing of discharge and 30-day and 1-year event-free survival after discharge among NSTEMI patients.Results: Among 20,410 NSTEMI patients, median length of stay was 7 (4, 12) days; 3,209 (15.7%) experienced a cardiac complication on days 0 to 2 and 1,322 (6.5%) were discharged without complications during hospital days 0 to 2. At the start of day 3, 15,879 patients (77.8%) were still hospitalized without complications. Of these, 1,689 (10.6%) were discharged event-free on day 3. Adjusted event-free survival rates of death or myocardial infarction from day 4 to 30 days after among the 1,689 patients was 99.1% compared with 93.1% for the 14,190 who remained hospitalized at the end of day 3. For 1-year mortality, these rates were 98.1% and 96.4%, respectively. Among 13,334 patients hospitalized without complications at the start of day 4, 1,706 were discharged event-free that day. Adjusted survival rates among these patients, compared with those still hospitalized at the end of day 4, were 98.0% versus 93.7% for 30-day death or myocardial infarction and 97.8% versus 96.1% for 1-year mortality.Conclusions: Patients with NSTEMI who had no serious complications during the first 2 hospital days were at low risk of subsequent short- and intermediate-term death or ischemic events. [ABSTRACT FROM AUTHOR]

Objectives In 13,038 patients with non–ST-segment elevation acute coronary syndrome undergoing index percutaneous coronary intervention (PCI) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndrome) and TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trials, the relationship between PCI-related myocardial infarction (MI) and 1-year mortality was assessed. Background The definition of PCI-related MI is controversial. The third universal definition of PCI-related MI requires cardiac troponin >5 times the 99th percentile of the normal reference limit from a stable or falling baseline and PCI-related clinical or angiographic complications. The definition from the Society for Cardiovascular Angiography and Interventions (SCAI) requires creatine kinase–MB elevation >10 times the upper limit of normal (or 5 times if new electrocardiographic Q waves are present). Implications of these definitions on prognosis, prevalence, and implementation are not established. Methods In our cohort of patients undergoing PCI, PCI-related MIs were classified using the third universal type 4a MI definition and SCAI criteria. In the subgroup of patients included in the angiographic core laboratory (ACL) substudy of EARLY ACS (n = 1,401) local investigator– versus ACL-reported angiographic complications were compared. Results Altogether, 2.0% of patients met third universal definition of PCI-related MI criteria, and 1.2% met SCAI criteria. One-year mortality was 3.3% with the third universal definition (hazard ratio: 1.96; 95% confidence interval: 1.24 to 3.10) and 5.3% with SCAI criteria (hazard ratio: 2.79; 95% confidence interval: 1.69 to 4.58; p < 0.001). Agreement between ACL and local investigators in detecting angiographic complications during PCI was overall moderate (κ = 0.53). Conclusions The third universal definition of MI and the SCAI definition were both associated with significant risk for mortality at 1 year. Suboptimal concordance was observed between ACL and local investigators in identifying patients with PCI complications detected on angiography. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRA·CER] [Study P04736]; NCT00527943 ; EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome [Study P03684AM2]; NCT00089895 ) [ABSTRACT FROM AUTHOR]

Background--Patients with chronic kidney disease (CKD) experience high rates of ischemic and bleeding events after percutaneous coronary intervention (PCI), complicating decisions surrounding dual antiplatelet therapy (DAPT). This study aims to determine the pattern and impact of various modes of DAPT cessation for patients with CKD undergoing PCI. Methods and Results--Patients from the PARIS registry (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) were grouped based on the presence of CKD defined as creatinine clearance <60 mL/min. After index PCI, time and mode of DAPT cessation (discontinuation, interruption, and disruption) and clinical outcomes (major adverse cardiac events, stent thrombosis, myocardial infarction, and major bleeding [Bleeding Academic Research Consortium type 3 or 5]) were reported. Over 2 years, patients with CKD (n=839) had higher adjusted risks for death (hazard ratio, 3.16; 95% confidence interval, 2.26-4.41), myocardial infarction (hazard ratio, 2.43; 95% confidence interval, 1.65-3.57), and major bleeding (hazard ratio, 2.21; 95% confidence interval, 1.53-3.19) compared with patients without CKD (n=3745). Rates of DAPT discontinuation within the first year after PCI and disruption were significantly higher for patients with CKD. However, DAPT interruption occurred with equal frequency. Associations between DAPT cessation mode and subsequent risk were not modified by CKD status. Findings were unchanged after propensity matching. Conclusions--Patients with CKD display high and comparable risks for both ischemic and bleeding events after PCI. Physicians are more likely to discontinue DAPT within the first year after PCI among patients with CKD, likely reflecting clinical preferences to avoid bleeding. Risks after DAPT cessation, irrespective of underlying mode, are not modified by the presence or absence of CKD. [ABSTRACT FROM AUTHOR]

Background: Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging.Methods: In the TRACER trial, patients with non-ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death.Results: Overall, 10.3% (n=1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n=82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n=17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P<.0001) than that of type 1 MI (vs. no MI, adj. HR 8.90, 95% CI 6.93-11.43; P<.0001).Conclusions: Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research. [ABSTRACT FROM AUTHOR]

Background--Elevated white blood cell (WBC) count is associated with increased major adverse cardiovascular events (MACE) in the setting of acute coronary syndrome. The aim of this study was to evaluate whether similar associations persist in an all-comers population of patients undergoing percutaneous coronary intervention in the contemporary era. Methods and Results--In the multicenter, prospective, observational PARIS study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry), 4222 patients who underwent percutaneous coronary intervention in the United States and Europe between July 1, 2009, and December 2, 2010, were evaluated. The associations between baseline WBC and MACE (composite of cardiac death, stent thrombosis, spontaneous myocardial infarction, or target lesion revascularization) at 24-month follow-up were analyzed using multivariable Cox regression. Patients with higher WBC were more often younger, smokers, and with less comorbid risk factors compared with those with lower WBC. After adjustment for baseline and procedural characteristics, WBC remained independently associated with MACE (hazard ratio [HR] per 103 cells/µL increase, 1.05 [95% confidence intervals (CI), 1.02-1.09]; P=0.001), cardiac death (HR, 1.10 [95% CI, 1.05-1.17]; P<0.001), and clinically indicated target revascularization (HR, 1.04 [95% CI, 1.00-1.09]; P=0.03) but not stent thrombosis (HR, 1.07 [95% CI, 0.99-1.16]; P=0.10) or spontaneous myocardial infarction (HR, 1.03 [95% CI, 0.97-1.09]; P=0.29). The association between WBC and MACE was consistent in acute coronary syndrome and non-acute coronary syndrome presentations (interaction P=0.15). Conclusions--Increased WBC is an independent predictor of MACE after percutaneous coronary intervention in a contemporary all-comers cohort. Further studies to delineate the underlying pathophysiologic role of elevated WBC across a spectrum of coronary artery disease presentations are warranted. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). Background Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. Methods Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. Results During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. Conclusions DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation. [ABSTRACT FROM AUTHOR]

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation is an emerging clinical problem. Currently, there is limited evidenced-based data on the optimal antithrombotic treatment regimen, including antiplatelet and anticoagulant therapies, for these high-risk patients with practice guidelines, thus, providing limited recommendations. Over the past years, expert consensus documents have provided guidance to clinicians on how to manage patients with atrial fibrillation undergoing percutaneous coronary intervention. Given the recent advancements in the field, the current document provides an updated opinion of selected North American experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention. In particular, this document provides the current views on (1) embolic/stroke risk, (2) ischemic/thrombotic cardiac risk, and (3) bleeding risk, which are pivotal for discerning the choice of antithrombotic therapy. In addition, we describe the recent advances in pharmacology, stent designs, and clinical trials relevant to the field. Ultimately, we provide expert consensus–derived recommendations, using a pragmatic approach, on the management of patients with atrial fibrillation undergoing percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Background: Albuminuria is associated with cardiovascular (CV) outcomes. We evaluated albuminuria, alone and in combination with estimated glomerular filtration rate (eGFR), as a predictor of mortality and CV morbidity in 12,944 patients with non-ST-segment elevation acute coronary syndromes.Methods: Baseline serum creatinine and urinary dipsticks were obtained, with albuminuria stratified into no/trace albuminuria, microalbuminuria (≥30 but <300 mg/dL), or macroalbuminuria (≥300 mg/dL). Kaplan-Meier rates and proportional Cox hazards models of CV death, overall mortality, CV death or myocardial infarction (MI), and bleeding were calculated. Incidence of acute kidney injury, identified by adverse event reporting and creatinine increase (absolute ≥0.3 mg/dL or relative ≥50%), was descriptively reported.Results: Both dipstick albuminuria and creatinine values were available in 9473 patients (73.2%). More patients with macroalbuminuria, versus no/trace albuminuria, had diabetes (66% vs 27%) or hypertension (86% vs 68%). Rates for CV death and overall mortality per strata were 3.1% and 4.8% (no/trace albuminuria); 5.8% and 9.0% (microalbuminuria); and 7.7% and 12.6% (macroalbuminuria) at 2 years of follow-up. Corresponding rates for CV death or MI were 12.2%, 16.9%, and 23.5%, respectively. Observed acute kidney injury rates were 0.6%, 1.2%, and 2.9% (n = 79), respectively. Adjusted HRs for macroalbuminuria on CV mortality were 1.65 (95% CI 1.15-2.37), and after adjustment with eGFR, 1.37 (95% CI 0.93-2.01). Corresponding HRs for overall mortality were 1.82 (95% CI 1.37-2.42) and 1.47 (95% CI 1.08-1.98).Conclusions: High-risk patients with non-ST-segment elevation acute coronary syndromes and albuminuria have increased morbidity and increased overall mortality independent of eGFR. [ABSTRACT FROM AUTHOR]

Background: Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety.Methods: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding.Results: The median age of the population was 64years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574).Conclusion: Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to compare the incidence and impact of cessation of dual-antiplatelet therapy (DAPT) in women and men treated with percutaneous coronary intervention. Background Nonadherence to cardiovascular medications and female sex are associated with worse outcomes. However, the patterns and impact of DAPT cessation in women compared with men following percutaneous coronary intervention have not been studied. Methods Baseline characteristics, patterns of DAPT cessation, and 2-year clinical outcomes were compared in 5,031 patients (1,279 women, 3,739 men) enrolled following successful percutaneous coronary intervention with stents in the PARIS (Patterns of Non-Adherence to Antiplatelet Regimens in Stented Patients) study. DAPT cessation was adjudicated as physician-guided discontinuation, interruption for surgery, or disruption due to bleeding or noncompliance. Clinical endpoints were major adverse cardiac events (a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, or clinically indicated target lesion revascularization), a second restricted definition of major adverse cardiac events excluding target lesion revascularization, and bleeding. Results DAPT cessation was more common in women than men (59.1% vs. 55.9%, p = 0.007) and comprised increased rates of discontinuation, disruption for bleeding, and disruption due to noncompliance. The impact of DAPT cessation was similar regardless of sex and varied according the mode; in particular, disruption was associated with increased risk for both ischemic and bleeding events. After adjusting for differences in baseline and treatment characteristics as well as DAPT cessation events, female sex remained an independent predictor of bleeding but not of ischemic events. Conclusions DAPT cessation was more common in women, but its impact was similar in women and men. Female sex was an independent predictor of bleeding but not of ischemic events after adjustment for differences in DAPT cessation and baseline and treatment characteristics. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to examine the independent associations between actionable bleeding (AB) and coronary thrombotic events (CTE) on mortality risk after percutaneous coronary intervention (PCI). Background The independent impact of AB and CTE on mortality risk after PCI remains poorly characterized. Methods A post hoc analysis was conducted of the PARIS (Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients) registry, a real-world cohort of 5,018 patients undergoing PCI with stent implantation. CTE included definite or probable stent thrombosis or myocardial infarction. AB was defined as Bleeding Academic Research Consortium type 2 or 3. Associations between CTE and AB, both of which were modeled as time-dependent covariates, and 2-year mortality risk were examined using extended Cox regression. Results Over 2 years, the cumulative incidence of CTE, AB, and all-cause mortality was 5.9% (n = 289), 8.1% (n = 391), and 4.7% (n = 227), respectively. Adjusted hazard ratios for mortality associated with CTE and AB were 3.3 (95% confidence interval: 2.2 to 4.9) and 3.5 (95% confidence interval: 2.3 to 5.4), respectively. Temporal gradients in risk after either event were highest in the first 30 days and declined rapidly thereafter. Thrombotic events occurring while patients were on versus off dual-antiplatelet therapy were associated with a higher mortality risk, whereas risk related to AB was not influenced by dual-antiplatelet therapy status at the time of bleeding. Conclusions Intracoronary thrombosis and AB are associated with mortality risks of comparable magnitude over a 2-year period after PCI, findings that might inform risk/benefit calculations for extension versus discontinuation of dual-antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Background--Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL. Methods and Results--Serial angiograms of 329 patients with acute coronary syndrome without ST-segment-elevation who underwent percutaneous coronary intervention at entry in the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRACER) and who met criteria for possible ST subsequent to the index event were reviewed by an ACL. The ACL was blinded to the assessment by both LIs and the CEC regarding the presence or absence of ST. CEC adjudication was based on Academic Research Consortium definitions of ST, using case report form data and source documents, including catheterization laboratory reports. The ACL, CEC, and LIs agreed on the presence or absence of ST in 52.9% events (ê=0.32; 95% confidence interval, 0.26-0.39). The ACL and CEC agreed on 82.7% of events (ê=0.57; 95% confidence interval, 0.47-0.67); the ACL and LIs agreed on 61.1% of events (ê=0.25; 95% confidence interval, 0.16-0.34); and the CEC and LIs agreed on 62% of events (ê=0.28; 95% confidence interval, 0.21-0.36). Conclusions--ST reporting by an ACL, a CEC, and LIs is discordant. The assessment of ST is more often detected by direct review of angiograms by an ACL. [ABSTRACT FROM AUTHOR]

Background: Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched.Methods and Results: Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non-ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61-75] versus 64 [interquartile range 56-72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, β-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan-Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%-7.6%] to 4.5% [95% confidence interval 4.0%-5.0%] among women and 6.3% [95% confidence interval 6.0%-6.7%] to 3.1% [95% confidence interval 2.9%-3.4%] among men during the 17-year period.Conclusions: The relative proportion of women in non-ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women. [ABSTRACT FROM AUTHOR]

Background In the TRACER trial, vorapaxar, a protease-activated receptor-1 antagonist, plus standard care in non–ST-segment elevation acute coronary syndrome (NSTE ACS) patients did not significantly reduce the primary composite end point but reduced a key secondary end point and significantly increased bleeding. History of peripheral artery disease (PAD) was a risk-enrichment inclusion criterion. We investigated the efficacy and safety of vorapaxar in NSTE ACS patients with documented PAD. Methods TRACER was a double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with NSTE ACS. Results In total, 936 (7.2%) patients had a history of PAD. Ischemic events occurred more frequently among patients with PAD (25.3%) versus no PAD (12.2%, P < .001), and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD (9.1%) versus no PAD (5.0%, P = .004). Similar rates of the composite end point (cardiovascular death, myocardial infarction, or stroke) occurred in patients with PAD treated with vorapaxar and placebo (21.7% vs 24.8%, P interaction = .787). Patients with PAD treated with vorapaxar, when compared with placebo, also had a numerical reduction in peripheral revascularization procedures (8.1% vs 9.0%, P = .158) and a lower extremity amputation rate (0.9% vs 1.5%, P = .107). Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD (hazard ratio 1.47, 95% CI 0.89-2.45) and without (hazard ratio 1.48, 95% CI 1.22-1.79; P interaction = .921). Conclusions Patients with NSTE ACS and PAD were at increased risk for ischemic events. Lower rates of ischemic end points, peripheral revascularization, and amputation with vorapaxar did not reach statistical significance but warrant further investigation. Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk. [ABSTRACT FROM AUTHOR]

Patients presenting for invasive cardiovascular procedures are frequently taking a variety of medications aimed to treat risk factors related to heart and vascular disease. During the procedure, antithrombotic, sedative, and analgesic medications are commonly needed, and after interventional procedures, new medications are often added for primary and secondary prevention of ischemic events. In addition to these prescribed medications, the use of over-the-counter drugs and supplements continues to rise. Most elderly patients, for example, are taking 5 or more prescribed medications and 1 or more supplements, and they often have some degree of renal insufficiency. This polypharmacy might result in drug–drug interactions that affect the balance of thrombotic and bleeding events during the procedure and during long-term treatment. Mixing of anticoagulants, for instance, might lead to periprocedural bleeding, and this is associated with an increase in long-term adverse events. Furthermore, the range of possible interactions with thienopyridine antiplatelets is of concern, because these drugs are essential to immediate and extended interventional success. The practical challenges in the field are great—some drug–drug interactions are likely present yet not well understood due to limited assays, whereas other interactions have well-described biological effects but seem to be more theoretical, because there is little to no clinical impact. Interventional providers need to be attentive to the potential for drug–drug interaction, the associated harm, and the appropriate action, if any, to minimize the potential for medication-related adverse events. This review will focus on drug–drug interactions that have the potential to affect procedural success, either through increases in immediate complications or compromising longer-term outcome. [ABSTRACT FROM AUTHOR]

The article examines whether external cardioversions (ECV) were associated with long-term mortality (LTM) and morbidity among patients in the Atrial Fibrillation (AF) Follow-up Investigation of Rhythm Management study. The researchers analyzed the data of the 4060 patients with AF particularly mortality, cardiovascular death, and hospitalizations after ECV. They found that ECV were not significantly associated with LTM but were related to increased hospitalizations from cardiac causes.

The article focuses on the effect of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors when used in non-ST-segment elevation acute coronary syndromes (NSTE ACS). The authors analyzed 12 randomized clinical trials that they assessed for tirofiban, eptifibatide and lamifiban. They found that an 11% reduction in 30-day death/myocardial infarction when upstream GP IIb/IIa inhibitor was used. The authors claim significant but modest ischemic benefit brought by the use of the inhibitor.

Background: Physicians will increasingly encounter patients who require rhythm management devices but have venous obstructions that prevent conventional access. Alternate access options, such as thoracotomy or transiliac approaches, exist but are associated with greater cost and morbidity. Objective: The purpose of this study is to describe a novel method of vascular access that allows prepectoral placement of conventional pacing and defibrillation leads in patients with complex central venous occlusions. Methods: Eight patients with central venous occlusions were referred for device implantation. Inside-out central venous access (IOCVA) was obtained via a percutaneous femoral approach. A catheter-dilator system was advanced via the right atrium to the most central point of venous occlusion. The occluded vein segment was punctured with a directionally guided needle, which was advanced along intravascular or extravascular tissue planes to the subclavian region. A solid wire needle was oriented toward the skin surface and advanced through the soft tissues until it exists from the body. The wire was used to pull rigid dilators through the occluded segment. Standard transvenous leads were implanted though the newly created channel. Results: All patients with total central venous occlusions (4 superior vena cava, 4 brachiocephalic and bilateral subclavian) had successful, prepectoral device implants (4 left-sided, 1 single-chamber, 4 dual-chamber, 3 biventricular). No procedure-related complications occurred. All patients had normal device function at follow-up of 485 ± 542 days. Conclusion: IOCVA is an effective method of pacemaker and defibrillator implantation for patients with central venous occlusions. Further clinical evaluation of this novel method is needed. [ABSTRACT FROM AUTHOR]

Background: The role of hormone replacement therapy (HRT) in the prevention of cardiovascular disease has been controversial. In large observational studies, HRT appears to lower cardiovascular disease risk. However, prospective randomized trials do not substantiate this. Methods: We sought to characterize the use of HRT in women presenting with acute myocardial infarction and to investigate an association between HRT and inhospital or 30-day outcomes among women enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries III (GUSTO-III) trial. Of the 15 059 patients in GUSTO-III, 4124 were women. Menopausal status, HRT use, and clinical outcomes data were prospectively collected. Results: Postmenopausal women taking HRT were significantly younger than those not taking HRT, and US women were more likely to be prescribed HRT than non-US women. While unadjusted 30-day mortality was substantially lower in HRT patients (6.1% vs 12.7%, P < .001), HRT use was not independently predictive of mortality after correcting for baseline differences (χ2 = 0.15, P = .70). Conclusion: Hormone replacement therapy appears to have no early mortality benefit in women sustaining acute myocardial infarction. These findings further challenge the role of HRT in cardiovascular medicine. [ABSTRACT FROM AUTHOR]

Background: Reperfusion with primary percutaneous intervention (PCI) in ST-segment elevation myocardial infarction leads to improved clinical outcomes. The contribution angiographic vs electrocardiographic reperfusion parameters confer on prognosis is unclear. Methods: A prespecified subset of the APEX-AMI trial patients was analyzed by independent angiographic and electrocardiographic core laboratories (n = 1,018). Angiographic reperfusion after PCI and electrocardiogram 30 minutes post-PCI were assessed. Results: Of the 941 patients in the angiographic substudy, 796 (85%) attained post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow 3 and 852 (91%) had TIMI Myocardial Perfusion Grade (TMPG) 2/3. There were 664 (71%) patients with residual ST elevation (ST-E) <2 mm. Ninety-day mortality and death/CHF/shock were lower in patients with TIMI flow 3 vs <3 (1.9% vs 6.2%, P = .002; 5.8% vs 10.4%, P = .044) and those with TMPG 2/3 vs 0/1 (2.0% vs 7.9%, P = .001; 6.0% vs 11.9%, P = .028). Patients with residual ST-E <2 mm had similar rates of mortality as those with ≥2 mm (2.3% vs 3.3%, P = .374) but lower rates of death/CHF/shock (5.2% vs 9.6%, P = .013). After multivariable adjustment, only post-PCI TMPG 2/3 was significantly associated with survival (P = .001), whereas residual ST-E (P = .606) and post-PCI TIMI flow grade (P = .086) were not. Conversely, residual ST-E ≥2 mm (P = .012) rather than angiographic reperfusion was associated with the composite of death/CHF/shock events. Conclusion: Angiographic and electrocardiographic estimates of reperfusion with primary PCI in ST-segment elevation myocardial infarction provide different and complementary predictions of morbidity and mortality. [Copyright &y& Elsevier]

Background: Because acute occlusion of coronary arteries supplying the inferolateral myocardium frequently eludes standard 12-lead electrocardiogram (ECG) diagnosis, these patients may present as non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Methods: We examined culprit artery occlusion among 1,957 NSTE-ACS patients in the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network trial who underwent diagnostic coronary angiography. We compared baseline characteristics, electrocardiographic findings, in-hospital treatment, and long-term outcomes between patients with and without occluded culprit arteries. Results: The culprit artery was occluded in 528 (27%) patients. Culprit lesions were more frequently identified in the inferolateral territory among patients with an occluded culprit artery (63%) compared with those with a nonoccluded artery (45%, P < .0001). Patients with an occluded culprit artery were younger, more often male, and more likely to have had a prior myocardial infarction. Despite similar in-hospital treatment, patients with an occluded culprit artery had larger infarcts (median peak creatine kinase-MB 4.3 vs 2.1 x upper limit of normal, P < .0001) and higher risk-adjusted 6-month mortality (hazard ratio 1.72, 95% CI 1.07-2.79). Conclusions: More than 25% of NSTE-ACS patients had an occluded culprit artery on angiography. These patients may represent ST-segment elevation myocardial infarction equivalents; thus, improved early risk stratification techniques would help more rapidly triage these high-risk patients to an early invasive management strategy. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia and heparin-induced thrombocytopenia (HIT) are potentially devastating paradoxical side effects of heparin therapy. We explored the evaluation, management, and clinical consequences of thrombocytopenia occurring during heparin therapy in diverse clinical settings. Methods: CATCH was a prospective observational study that enrolled 3,536 patients in 48 US hospitals. Data were collected on 3 strata: patients receiving any form of heparin for ≥96 hours (n = 2,420); cardiac care unit (CCU) patients treated with heparin who developed thrombocytopenia (n = 1,090); patients who had an HIT assay performed (n = 449). Results: Thrombocytopenia occurred in 36.4% of patients in the prolonged heparin stratum and was associated with an increased risk of death or thromboembolic complication (OR 1.5, 95% CI 1.2-1.9). Among a subset of patients whose clinical presentation suggested they were at high risk for HIT, suspicion for HIT was uncommon (prolonged heparin stratum 19.8%, CCU stratum 37.6%) and often did not arise until ≥1 day after patients developed thrombocytopenia. Often patients were not evaluated for HIT until after they had had a thromboembolic complication (prolonged heparin stratum 43.8%, CCU stratum 61%). Even after HIT was suspected, patients often continued to receive heparin. Direct thrombin inhibitor use was infrequent (prolonged heparin stratum 29.4%, CCU stratum 35.6%). Among the few patients who underwent evaluation, HIT was confirmed in 46.7% of the prolonged heparin stratum and 31.4% of the CCU stratum. Conclusions: Thrombocytopenia is common among patients receiving heparin, and it is associated with substantial risk for catastrophic complications. Despite the high risk for HIT in this population, recognition, evaluation, and appropriate treatment are infrequent and delayed. [Copyright &y& Elsevier]

Background: Because acute occlusion of coronary arteries supplying the inferolateral myocardium frequently eludes standard 12-lead electrocardiogram (ECG) diagnosis, these patients may present as non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Methods: We examined culprit artery occlusion among 1,957 NSTE-ACS patients in the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network trial who underwent diagnostic coronary angiography. We compared baseline characteristics, electrocardiographic findings, in-hospital treatment, and long-term outcomes between patients with and without occluded culprit arteries. Results: The culprit artery was occluded in 528 (27%) patients. Culprit lesions were more frequently identified in the inferolateral territory among patients with an occluded culprit artery (63%) compared with those with a nonoccluded artery (45%, P < .0001). Patients with an occluded culprit artery were younger, more often male, and more likely to have had a prior myocardial infarction. Despite similar in-hospital treatment, patients with an occluded culprit artery had larger infarcts (median peak creatine kinase–MB 4.3 vs 2.1 × upper limit of normal, P < .0001) and higher risk-adjusted 6-month mortality (hazard ratio 1.72, 95% CI 1.07-2.79). Conclusions: More than 25% of NSTE-ACS patients had an occluded culprit artery on angiography. These patients may represent ST-segment elevation myocardial infarction equivalents; thus, improved early risk stratification techniques would help more rapidly triage these high-risk patients to an early invasive management strategy. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate ischemic and bleeding outcomes in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Background: Previous studies have shown that CKD is associated with poor outcomes after PCI. However, these studies were largely conducted before the introduction of DES and aggressive antithrombotic therapy or were performed in the setting of randomized trials. With data from a contemporary registry, we evaluated the influence of CKD on major cardiovascular events and bleeding complications in unselected “real-world” patients undergoing PCI. Methods: Data from 4,791 patients enrolled in the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) Registry between July 2004 and September 2005 were analyzed. Patients were stratified into 4 groups: creatinine clearance (CrCl) >75, 50 to 75, 30 to 49 and <30 ml/min. Results: During the index hospital stay, there was a step-wise increase in bleeding complications with decreasing CrCl (3.3%, 5.0%, 8.8%, and 14.3%; p < 0.0001 for trend). Lower CrCl was also associated with more frequent death or myocardial infarction (MI) during the initial hospital stay (p = 0.001) and at 1 year (p < 0.001). These findings were confirmed in multivariate analyses that adjusted for baseline differences in demographic, clinical, and angiographic factors. Use of guideline-recommended medications at 1 year, including aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and statins, also decreased with declining renal function. Conclusions: Renal function is an independent and powerful predictor of bleeding and ischemic complications in the era of DES and contemporary antithrombotic therapy in patients undergoing PCI. The low use of guideline-recommended drugs among patients with CKD undergoing PCI might contribute to these adverse outcomes and warrants further evaluation. [Copyright &y& Elsevier]

Background: Renal function significantly impacts morbidity and mortality after a percutaneous coronary intervention. Platelet glycoprotein (GP) IIb/IIIa inhibitors reduce ischemic complications during percutaneous coronary intervention; little is known of whether their safety and efficacy are influenced by renal function. In particular, whether outcome differences exist between agents that are renally excreted (tirofiban) or not (abciximab) in patients with mild renal impairment is not known. Methods: The TARGET trial randomized 4623 patients to tirofiban or abciximab. In this analysis, patients were grouped in creatinine clearance quartiles (<70, 70-90, 90-114, >114 mL/min) and analyzed for efficacy and bleeding risk. Univariate and multivariate analyses were performed to identify interactions between GP IIb/IIIa inhibitor used and creatinine clearance with respect to ischemic outcomes and bleeding. Results: Using unadjusted logistic regression tests for trend, 30-day death/myocardial infarction/urgent target vessel revascularization was greater in patients with lower creatinine clearances (7.3%, 8.5%, 5.1%, and 5.8%, P = .005), as were both major and minor bleeding. There was no interaction between assigned GP IIb/IIIa inhibitor, creatinine clearance and ischemic outcome, major bleeding or minor bleeding. Conclusions: Both ischemic and bleeding complications are highest in the lowest creatinine clearance quartile of patients treated with GP IIb/IIIa inhibitors. Although tirofiban is renally cleared and abciximab is not, there was no interaction between these GP IIb/IIIa inhibitors and creatinine clearance regarding ischemic or bleeding events. [Copyright &y& Elsevier]

Background It is uncertain how aggressively patients should be monitored and admitted to the hospital for chest pain syndromes and if the monitoring itself affects patient care, process, or outcomes. We assessed the appropriateness of care based on retrospective analysis of admission bed assignment (nonmonitored vs monitored) and Thrombolysis in Myocardial Infarction (TIMI) risk score in patients from the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. Methods Baseline characteristics, process of care, and outcomes were compared among 2939 patients admitted to 1 of 35 hospitals in the United States. Patients were stratified into low (0-2), intermediate (3 or 4), and high (5-7) risk based on TIMI risk score. Results Among the patients, 92 (3%) were admitted to the cardiac care unit (CCU), 1602 (56%) were admitted to the telemetry unit, and 1163 (41%) were admitted to an unmonitored bed. Paradoxically, high-risk patients comprised only 1% of those in the CCU, 5% of those in telemetry, and 10% of those in nonmonitored units. Conversely, low-risk patients were 64% of those in the CCU, 53% of those in telemetry, and 42% of those in unmonitored beds. Procedures were done more often on patients admitted to nonmonitored units than those on telemetry or in the CCU irrespective of TIMI risk score. Conclusions This registry suggests that triage of patients does not routinely follow the risk-based approach suggested in the American College of Cardiology and American Heart Association guidelines and could therefore potentially lead to inefficiencies in care. Better implementation of risk stratification for acute coronary syndrome evaluation and management is necessary. (Am Heart J 2005;149:1-6.) [ABSTRACT FROM AUTHOR]

Background Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown.Methods In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously.Findings At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14·8%) patients who received tirofiban and 345 (14·3%) patients who received abciximab (hazard ratio 1·04, 95% CI 0·90–1·21; p=0·591). The rates for the individual endpoints were 191 (8·0%) versus 159 (6·6%) for myocardial infarction (hazard ratio 1·21, 95% CI 0·98–1·50; p=0·074), 26 (1·1%) versus 25 (1·0%) for death (1·04, 0·60–1·80; p=0·893), and 194 (8·1%) versus 208 (8·6%) for target-vessel revascularisation (0·93, 0·77–1·14; p=0·495).Interpretation At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation. [Copyright &y& Elsevier]