Faculty Bibliography

BACKGROUND:Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD. OBJECTIVES/OBJECTIVE:The aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial. METHODS:Cox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection. RESULTS:EUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex. CONCLUSIONS:Although women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).

In the original article. The third author name is incorrect. The correct name is Nicholas J. Leeper.

INTRODUCTION/BACKGROUND:Collectively, coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent and are associated with increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Improved ability to identify those at highest risk of these events may help optimize secondary prevention efforts in this population. METHODS:Using the Optum Integrated Database, a healthcare claims database linked to electronic medical records (EMR), we identified patients with CAD and/or PAD between January 1, 2009, and September 30, 2016. Index date was the earliest date on which chronic and stable disease was established. Follow-up ran from index date until earliest of patient death, plan disenrollment, or end of study. We developed multivariate Cox proportional hazards models to identify predictors of MACE and/or MALE, limited to measures presumed available to clinicians during patient encounters (e.g., age, presence of selected comorbidities). RESULTS: = 0.98), ranging from 2.3 per 100 PYs among those without predictors (4.9% of patients) to 18.7 per 100 PYs among those with ≥ 6 (6.9%). Patients with ≥ 1 predictor experienced 7.4 MACE and/or MALE per 100 PYs. CONCLUSION/CONCLUSIONS:Readily identifiable predictors can be used to identify subgroups with chronic CAD and/or PAD at elevated risk of MACE and/or MALE. Further research is required to understand the degree to which these subgroups may benefit from early identification and treatment with secondary prevention therapies. FUNDING/BACKGROUND:Janssen Pharmaceuticals.

Introduction - Critical limb ischemia (CLI) implies a heightened risk for cardiovascular morbidity and mortality. Methods - The EUCLID trial (NCT01732822) investigated the effect of antithrombotic monotherapy, ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily, in patients with symptomatic peripheral arterial disease (PAD). Inclusion criteria were previous lower extremity revascularization (LER) or ankle-brachial index (ABI) <=0.80, randomizing 13,885 patients. Ticagrelor was not superior to clopidogrel in the reduction of cardiovascular events, nor did major bleeding differ between groups. The present study focuses on patients with CLI at baseline, defined by rest pain, minor or major tissue loss. Results - At baseline 643 patients (4.6 %) had CLI (Rutherford 4 (58.8%), Rutherford 5-6 (41.2%)). The proportion of patients with CLI in the LER group (351/7873, 4.5%) or low ABI group (292/6009, 4.9%) was similar.Diabetes mellitus was more common in the CLI group (49.3% vs 38.0%, p<0.0001), while a history of coronary artery disease was more common for the non-CLI group (29.2% vs 25.3%, p=0.035). A history of carotid disease was more frequent in non-CLI patients (18.0% vs 12.1%, p=0.0002) and a corresponding relationship was recorded for hypertension (non-CLI 78.4%, CLI 74.2%, p=0.01). Before randomization, more CLI than non-CLI patients were on clopidogrel (40.0% vs 31.8%, p<0.0001) whereas aspirin treatment was more common in the non-CLI group (67.3% vs 55.5%, p<0.0001). Dual antiplatelet therapy (aspirin and clopidogrel) was used by 16.2 % of CLI patients and 16.3 % of the non-CLI group. Statins were used by 73.8% of non-CLI patients, and 64.1% of the CLI group (p<0.0001). A history of major amputation was more common in patients with CLI (10.3%) compared to non-CLI patients (2.1%), p<0.0001. The primary efficacy endpoint, cardiovascular death, MI or ischemic stroke occurred significantly more frequently among CLI patients with a rate of 8.85 versus 4.28 per 100 patient-years (HR 2.07(1.72-2.48), p<0.0001; Fig), and this difference remained significant after adjustment for baseline characteristics (HR 1.43(1.16-1.76), p=0.0009). When including acute limb ischemia requiring hospitalization with MACE, significant differences remained, also after adjustment for baseline characteristics (HR 1.38(1.13-1.69), p=0.0016). LER was more common in CLI compared with non-CLI patients (HR 1.29(1.05-1.59), p=0.018), the difference not remaining significant after adjustment (HR 1.19(0.96-1.49), p=0.12). Bleeding did not differ between patients with and without CLI.The primary efficacy endpoint did not differ between ticagrelor and clopidogrel treated patients in the respective CLI and non-CLI groups, nor did bleeding. [Formula presented] Conclusion - Patients suffering CLI represented nearly 5% of patients enrolled in the EUCLID trial. The low amputation rate at baseline suggests milder forms of CLI dominated. CLI patients had a 2-fold higher rate of cardiovascular mortality and morbidity compared to non-CLI patients. Further efforts are required to reduce the risk for cardiovascular events in PAD, especially in patients with CLI.
Copyright

New-onset heart failure (HF) is associated with cardiovascular morbidity and mortality. It is uncertain to what extent HF confers an increased risk of venous thromboembolism (VTE). Adults ≥65 years old hospitalized with a new diagnosis of HF were identified from Medicare claims from 2007-2013. We identified the incidence, predictors and outcomes of VTE in HF. We compared VTE incidence during follow-up after HF hospitalization with a corresponding period 1-year prior to the HF diagnosis. Among 207,535 patients with a new HF diagnosis, the cumulative incidence of VTE was 1.4%, 2.5%, and 10.5% at 30 days, 1 year, and 5 years, respectively. The odds of VTE were greatest immediately after new-onset HF and steadily declined over time (OR 2.2 [95% CI 2.0-2.3], OR 1.5 [1.4-1.7], and OR 1.2 [1.2-1.3] at 0-30 days, 4-6 months, and 7-9 months, respectively). Over 26-month follow-up, patients with HF were at two-fold higher risk of VTE than patients without HF (adjusted HR 2.31 [2.18-2.45]). VTE during follow-up was associated with long-term mortality (adjusted HR 1.60, 95% CI 1.56-1.64). In conclusion, patients with HF are at increased risk of VTE early after a new HF diagnosis. VTE in patients with HF is associated with long-term mortality.

BACKGROUND:Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors of major bleeding, and risk of major adverse cardiovascular events (MACE) following major bleeding events. METHODS:EUCLID, a multicenter randomized controlled trial of 13,885 patients with symptomatic PAD, compared ticagrelor with clopidogrel for the prevention of MACE. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Baseline characteristics were used to develop a multivariable model to determine factors associated with TIMI major bleeding. The occurrence and timing of MACE relative to a first major bleeding event were determined. RESULTS:TIMI major bleeding occurred in 2.3% of participants overall (0.94 event/100 patient-years). There was no significant difference in major bleeding rates by treatment assignment. Factors associated with TIMI major bleeding included older age, geographic region, Rutherford class, and β-blocker use. Patients with TIMI major bleeding postrandomization had an increased risk of MACE (hazard ratio [HR] 4.46; 95% CI 3.40-5.84; P < .0001) compared with those without major bleeding; the association was strongest within 30 days after a bleeding event. CONCLUSIONS:In patients with symptomatic PAD, 0.94 major bleeding event/100 patient-years was observed and associated with older age, residing in North America, disease severity, and β-blocker use. Patients who had a major bleeding event were significantly more likely to experience MACE, especially within the first 30 days, when compared with patients who did not have major bleeding.