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Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. Methods: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. Results: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index P =0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24–0.85]; P =0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40–0.83]; P =0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use ( P interaction=0.59). Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Acute aortic syndromes, classified into aortic dissection, intramural hematoma, and penetrating aortic ulcer, are associated with high early mortality for which early diagnosis and management are crucial to optimize outcomes. Patients often present with nonspecific clinical symptoms and signs; therefore, it is important for providers to maintain a high index of suspicion for acute aortic syndromes. Electrocardiogram-gated computed tomographic angiography of the chest, abdomen, and pelvis is currently the most practical imaging modality for diagnosis and identification of complications. Evolution in surgical techniques and the development of aortic endografts have improved patient outcomes, but randomized trials are still needed.

Background Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. Objectives This study assessed DCD safety and effectiveness in LER for PAD. Methods VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespecified DCD analyses, primary safety and effectiveness outcomes were mortality and unplanned index limb revascularization (UILR). Major adverse limb events (MALE) were a secondary outcome. Inverse probability treatment weighting was used to account for each subject's propensity for DCD treatment. Effects of rivaroxaban were assessed with Cox proportional hazards models. Results Among 4,316 patients who underwent LER, 3,478 (80.6%) were treated for claudication, and 1,342 (31.1%) received DCDs. Median follow-up was 31 months, vital status was ascertained in 99.6% of patients, and there were 394 deaths. After weighting, DCDs were not associated with mortality (HR: 0.95; 95% CI: 0.83-1.09) or MALE (HR: 1.08; 95% CI: 0.90-1.30) but were associated with reduced UILR (3-year Kaplan-Meier: 21.5% vs 24.6%; HR: 0.84; 95% CI: 0.76-0.92). Irrespective of DCD use, consistent benefit of rivaroxaban for composite cardiovascular and limb events (Pinteraction = 0.88) and safety of rivaroxaban with respect to bleeding (Pinteraction = 0.57) were observed. Conclusions In >4,000 patients with PAD who underwent LER, DCDs were not associated with mortality or MALE but were associated with persistent reduction in UILR. These findings provide insight into the safety and effectiveness of DCDs in PAD. (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD [VOYAGER PAD]; NCT02504216 )

Aims In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk–benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. Methods and results The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan–Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). Conclusion Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Background Patients with peripheral artery disease (PAD) treated with lower extremity revascularization are at increased risk of major atherothrombotic vascular events (acute limb ischemia (ALI), major non-traumatic lower-limb amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular (CV)-related death). This study assessed the incidence of major atherothrombotic vascular events, venous thromboembolism (VTE) events and rates of subsequent lower extremity revascularizations in the real-world among patients with PAD after revascularization. Methods Patients aged ≥50 years with PAD who underwent peripheral revascularization were identified from Optum Clinformatics Data Mart claims database (Q1/2014-Q2/2019). The first lower extremity revascularization after PAD diagnosis was defined as index date. Incidence rates of major atherothrombotic vascular events (i.e., composite of ALI, major non-traumatic lower-limb amputation, MI, ischemic stroke, and CV-related death) and VTE were assessed during follow-up as the number of events divided by patient-years of observation (censored at the first event). Rates of subsequent revascularizations and VTE were estimated overall and compared between patients with major atherothrombotic vascular events and those without. Results Of the 38,439 patients included, 6,675 (17.4%) had a major atherothrombotic vascular event during a median follow-up of 1.0 year. The composite major atherothrombotic vascular and VTE incidence rates were 13.81/100 patient years and 1.77/100 patient years, respectively, and 40.2% of patients experienced subsequent revascularizations. Patients with a post-revascularization major atherothrombotic vascular event had significantly higher rates of subsequent revascularizations (64.6% vs. 35.1%, standardized difference [SD] ≥10%) and VTE (4.6% vs. 2.1%, SD ≥10%) versus those without. Conclusion One-in-six PAD patients aged ≥50 years who underwent peripheral revascularization experienced a major atherothrombotic vascular event within one year, and consequently, experienced higher rates of subsequent revascularizations compared with those without a major atherothrombotic vascular event post-revascularization. These findings highlight the need to improve strategies to prevent major atherothrombotic vascular events after revascularization.

Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.This study sought to evaluate the total burden of vascular events in patients with PAD after LER and the efficacy of low-dose rivaroxaban on total events.VOYAGER PAD randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. The primary endpoint was time to first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism. HRs were estimated by marginal proportional hazards models.Among 6,564 randomized events, there were 4,714 total first and subsequent vascular events including 1,614 primary endpoint events and 3,100 other vascular events. Rivaroxaban reduced total primary endpoint events (HR: 0.86; 95% CI: 0.75-0.98; P = 0.02) and total vascular events (HR: 0.86; 95% CI: 0.79-0.95; P = 0.003). An estimated 4.4 primary and 12.5 vascular events per 100 participants were avoided with rivaroxaban over 3 years.Patients with symptomatic PAD who are undergoing LER have a high total event burden that is significantly reduced with rivaroxaban. Total event reduction may be a useful metric to quantify the efficacy of rivaroxaban in this setting. (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities [VOYAGER PAD]; NCT02504216).

A 69-year-old man underwent coronary angiography 7 years after coronary artery bypass. Saphenous vein graft spasm was observed during contrast injection, resulting in ventricular fibrillation. Angiography 6 years later showed graft patency. Vein graft spasm after coronary artery bypass grafting is rarely described. Further investigation is needed regarding incidence, mechanism, and clinical outcomes. (Level of Difficulty: Beginner.)

Peripheral artery disease (PAD), often treated with lower extremity revascularization, is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major non-traumatic lower-limb amputation, myocardial infarction [MI], ischemic stroke, cardiovascular death). This study aims to assess healthcare resource utilization and costs of such events among patients with PAD after revascularization.Patients aged ≥50 years with PAD who were treated with lower-extremity revascularization were identified from Optum Clinformatics Data Mart claims database (01/2014-06/2019). The first lower extremity revascularization after PAD diagnosis was defined as the index date. Patients had ≥6 months of health plan enrollment before the index date. Patients were followed until the earliest of 1) end of enrollment or data; 2) diagnosis of atrial fibrillation or venous thromboembolism; or 3) oral anticoagulant use. All-cause healthcare resource use per-patient-year was compared before and after a major atherothrombotic vascular event post-revascularization among those with an event. Additionally, event-related healthcare costs per-patient-year were reported for each event type.Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event. On average, patients were observed for 7.3 months before an event and 6.2 months after an event. Patients with an event had significantly higher all-cause healthcare resource use versus similar metrics pre-event (e.g. inpatient visits among those with ALI: 3.5 ± 5.8 post-event vs. 2.0 ± 8.1 pre-event,Data do not contain clinical information. Additionally, results are limited to commercially insured and Medicare Advantage beneficiaries.Patients with PAD who experience major atherothrombotic vascular events post-revascularization have considerably higher healthcare resource use and costs compared with similar metrics pre-event. Therefore, reducing the rate of such events could reduce overall healthcare costs for this population.

Background: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. Methods: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization. Results: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71–1.01) with clopidogrel and 0.86 (95% CI, 0.73–1.01) without clopidogrel without statistical heterogeneity ( P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14–1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22–1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use ( P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44–7.13]) compared with shorter durations of clopidogrel ( P for trend=0.06). Conclusions: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02504216.

Background Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and ...

BACKGROUND: Patients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.OBJECTIVES: 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).

Background: Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated. Methods: EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized patients with peripheral artery disease to ticagrelor versus clopidogrel. Enrollment criteria included an ankle-brachial index ≤0.80 or previous lower extremity revascularization. Patients were grouped according to the primary outcome, postrandomization ALI hospitalization. Baseline factors associated with ALI were identified using Cox proportional hazards modeling. Models with ALI hospitalization as a time-dependent covariate were developed for secondary outcomes of major adverse cardiovascular events (myocardial infarction, cardiovascular death, ischemic stroke), all-cause mortality, and major amputation. Results: Among 13 885 patients, 1.7% (n=232) had 293 ALI hospitalizations (0.8 per 100 patient-years). Patients with versus without ALI were younger and more often had previous peripheral revascularization and lower baseline ankle-brachial index. Treatment during ALI hospitalization included endovascular revascularization (39.2%, n=115), surgical bypass (24.6%, n=72), and major amputation (13.0%, n=38). After multivariable adjustment, any previous peripheral revascularization (Hazard Ratio [HR] 4.7, 95% CI 3.3–6.8, P P =0.03), and baseline ankle-brachial index ≤0.60 (HR 1.3 per 0.10 decrease, 95% CI 1.1–1.5, P P =0.02) and baseline statin use (HR 0.7, 95% CI 0.5–0.9, P P =0.04), all-cause mortality (adjusted HR 3.3, 95% CI 2.4–4.6, P P Conclusions: Previous peripheral revascularization, baseline atrial fibrillation, and lower ankle-brachial index identify peripheral artery disease patients at heightened risk for ALI, an event associated with subsequent cardiovascular and limb-related morbidity and mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.

BACKGROUND: Meta-analyses of randomised trials of paclitaxel-coated peripheral devices found an association with worse long-term survival. We assessed long-term mortality in patients treated with drug-coated devices insured by Medicare Advantage (MA), an alternative to traditional Medicare that represents >30% of the Medicare eligible population. METHODS: Patients treated with or without drug-coated devices for femoropopliteal artery revascularisation from 4/2015–12/2017 were studied using Optum’s De-identified Clinformatics® Datamart Database. Mortality was assessed through December 2019 using Kaplan Meier cumulative mortality curves and Cox-proportional hazard models. Inverse probability of treatment weighting was used to adjust for differences between groups. RESULTS: Of 16,796 patients revascularised, 4,427 (26.4%) were treated with drug-coated devices: 3,600 (81.3%) balloons and 827 (18.7%) stents. The median follow-up was 2.66 years (IQR 2.02–3.52). Treatment with drug-coated devices was associated with similar long-term mortality as nondrug-coated devices (adjusted HR 1.03; 95%CI=0.96–1.10; P=0.39). Results were comparable for patients treated with balloons alone (adjusted HR 1.00; 95%CI=0.92–1.08; P=0.96) or stents (adjusted HR 1.02; 95%CI=0.88–1.18; P=0.78). These findings did not differ based on treatment setting, disease severity, age, sex or comorbidity burden (interaction P>0.05 for all). CONCLUSIONS: In this large cohort, there was no evidence of increased long-term mortality following treatment with drug-coated devices. CONDENSED ABSTRACT: Meta-analyses of randomised trials of paclitaxel-coated peripheral devices found an association with worse long-term survival. To further evaluate device safety, Medicare Advantage claims data from 4/2015–12/2017 were used to identify patients treated with drug-coated and nondrug-coated devices. Inverse probability of treatment weighting was used for adjustment. Of 16,796 patients, 26.4% were treated with drug-coated devices. Median follow-up was 2.66 years (IQR 2.02 – 3.52). Treatment with drug-coated devices was associated with similar risk of long-term mortality as nondrug-coated devices (HR 1.03; 95%CI=0.96–1.10; P=0.39). In this large cohort, there was no evidence of increased long-term mortality following treatment with drug-coated devices.

Background: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Results: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method ( P -interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67–0.98]; P =0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding ( P -interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding ( P -interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39–1.95]; P =0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage ( P =0.95) and postprocedural bleeding requiring intervention ( P =0.93) was not significantly increased. Conclusions: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov ; Unique Identifier: NCT02504216.

Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice). In the past several years, a body of evidence has indicated that these perceptions are incorrect. Several studies have consistently demonstrated that many patients with PAD are not receiving evidence-based therapies. Thus, this scientific statement provides an update for health care professionals regarding contemporary epidemiology (eg, prevalence, temporal trends, risk factors, and complications) of PAD, the present status of diagnosis (physiological tests and imaging modalities), and the major gaps in the management of PAD (eg, medications, exercise therapy, and revascularization). The statement also lists key gaps in research, clinical practice, and implementation related to PAD. Orchestrated efforts among different parties (eg, health care providers, researchers, expert organizations, and health care organizations) will be needed to increase the awareness and understanding of PAD and improve the diagnostic approaches, management, and prognosis of PAD.

Background: A reduced ankle-brachial index (ABI) is a measure of atherosclerosis and is associated with ischemic risk in the general population. Whether this relationship is maintained in peripheral artery disease after lower extremity revascularization (LER), which can modify ABI, is unknown. Methods: The EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) enrolled 13 885 patients with symptomatic peripheral artery disease; 57% with prior LER, and 43% with ABI ≤0.80. The primary major adverse cardiovascular events (MACE) outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Major adverse limb events (MALE) included acute limb ischemia and major amputation. An adjusted Cox proportional hazards model demonstrated a nonlinear relationship between ABI and outcomes. A restricted cubic spline model with 4 knots was developed to identify the best fitting model to describe the relationship between ABI and MACE and MALE risk. Results: Baseline ABI (mean±SD) was 0.77±0.21 in participants with prior LER and 0.63±0.14 in those without prior LER ( P P P P =0.0004) and MALE (hazard ratio, 1.27 [95% CI, 1.08–1.49]; P =0.003). Conclusions: Patients with established peripheral artery disease, particularly those with prior LER, have an increased risk of MACE and MALE. The ABI remains a strong predictor of MACE and MALE ischemic events with an inverse relationship below an ABI threshold for patients with and without prior LER. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk.The authors examined LLT use and actual achieved LDL-C in PAD.PAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C70 mg/dl were identified with multivariable logistic regression.Among 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C 70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C 70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was 70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C 70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia.In PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.

Introduction: Chronic kidney disease (CKD) is common among patients undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD) and identifies a population at high risk for adverse outcomes. The VOYAGER PAD trial demonstrated the efficacy of rivaroxaban in PAD patients after LER on a composite of cardiovascular (CV) and limb ischemic events (HR 0.85 vs placebo, 95% CI 0.76-0.96; p=0.009); this analysis examines the prespecified subgroup of patients with CKD. Methods: VOYAGER PAD (NCT02504216) was a double-blind, placebo-controlled trial which randomized PAD patients with recent LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary endpoint was a composite of acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding. Analysis of the intention-to-treat population utilized Kaplan Meier estimates and Cox proportional-hazards models. Results: Among 6319 VOYAGER patients with baseline estimated glomerular filtration rate (eGFR), 21% were 2 . During 28-month (median) follow up, patients with CKD had a higher rate of major CV and limb events: placebo group 10.0 events/100 patient-years (95% CI 8.5, 11.8) for eGFR Conclusions: Rivaroxaban reduced major CV and limb events in patients with PAD undergoing LER, including those with CKD, a particularly high-risk population.

Introduction: Peripheral artery disease (PAD), frequently requiring lower-extremity revascularization (LER), is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major amputation of vascular etiology, myocardial infarction [MI], ischemic stroke [IS], cardiovascular [CV] death). Understanding the incidence and healthcare costs of such events in PAD patients post-revascularization may be important in translation. Methods: Patients with PAD who underwent LER were identified from Optum Clinformatics Data Mart claims database (Q1 2014 - Q2 2019). The first LER was considered index. Patients were required to be ≥50 years old at index with ≥6 months of prior health plan enrollment. Patients with IS, atrial fibrillation (AF), venous thromboembolism (VTE), intracranial hemorrhage, ESRD, or oral anticoagulant (OAC) use pre-index; or diagnoses of MI 30 days or ALI 14 days pre-index were excluded. Patients were followed until the earliest of 1) end of enrollment/data; 2) diagnosis of AF or VTE; or 3) OAC use. For each major vascular event, the incidence rate was assessed as the number of first events divided by patient-years of observation. Event-related healthcare costs per-patient-year (PPY) were also reported. Results: Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event over a median follow-up of 1.0 years (IQR: 0.4-2.1). The composite event incidence rate was 13.81 per 100 patient years [ALI: 5.51; lower-limb amputation: 5.15; MI: 3.19; IS: 2.06; CV-related death: 0.88]. PPY event-related costs ranged from $57,825 for IS to $108,302 for lower-limb amputation (Figure). Conclusions: One in six PAD patients have a major atherothrombotic vascular event within one year post-LER. Costs of these events are high, particularly for limb complications. Therefore, reducing the rate of such events could reduce the overall healthcare costs for this population.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Strategies that lower LDL-C levels reduce this risk. Hypothesis: We hypothesized that real-world PAD patients are overall undertreated with lipid lowering therapies (LLT) but that LLT use and achieved LDL-C are improved in high risk patients with ischemic events. Methods: Patients with PAD in the MarketScan database linked to PROGNOS lab data from January 1, 2014 through December 31, 2018 were examined. Outcomes included use of LLT, defined as high intensity (HI) (high intensity statin, any statin plus ezetimibe, or any use of a PCSK9 inhibitor), low intensity (LI) (any other lipid regimen), or no therapy, and follow up LDL-C level. Goal LDL-C was defined as Results: Among 18,747 PAD patients, 25% were on HI LLT, 43% were on LI LLT, and 32% were on no therapy at baseline (Figure A). The median LDL-C was 91 mg/dl (IQR 70, 118), and 25% of patients were at goal (Figure B). After a median follow up of 18 months, use of HI LLT increased by 4%, the median LDL-C decreased by 5 mg/dl, and an additional 3% of patients were at goal LDL-C. Greater use of HI LLT was observed among patients with a MACE (55%) or MALE (41%) event during follow up compared with patients without an ischemic event (26%) during follow up (Figure C). Follow up LDL-C levels remained above goal for most patients (post-MACE: median LDL-C 77 mg/dl, 42% patients at goal; post-MALE: median LDL-C 80 mg/dl, 36% patients at goal). Conclusions: In PAD patients, use of LLT is suboptimal, and LDL-C levels remain elevated. After an ischemic event, LLT use is intensified, with greater use of HI LLT observed after MACE than MALE. Despite this, LLT remains underutilized, with >50% of patients not at goal LDL-C. Strategies to better implement proven therapies to reduce risk in this high risk population are needed.

Background: Prior studies suggest that atherosclerotic vascular disease may be associated with risk of venous thromboembolism (VTE), though the relationship remains uncertain and has not been well-studied in peripheral artery disease (PAD) after lower extremity revascularization (LER). Hypothesis: We hypothesized that patients with PAD undergoing LER are at risk for VTE and that this risk may be reduced by low-dose rivaroxaban plus aspirin versus aspirin alone. Methods: VOYAGER PAD randomized 6,564 PAD patients undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. Clopidogrel was allowed for up to 6 months. Patients could not be enrolled if they had an indication for therapeutic anticoagulation, including secondary prevention of VTE. Symptomatic VTE was a prespecified secondary endpoint. Results: Over a median of 28 months, there were 66 patients with VTE. In patients randomized to placebo, risk for VTE accrued steadily after randomization at a rate of ~0.5% per year resulting in a 3-year rate of 1.66%. Compared with placebo, rivaroxaban reduced the risk of VTE by 39% (HR 0.61, 95% CI 0.37-1.00, p=0.047), with benefit apparent early and sustained over time (Figure). The efficacy of rivaroxaban was not modified by use of clopidogrel at randomization (without clopidogrel HR 0.55, 95% CI 0.29, 1.07; with clopidogrel HR 0.69, 95% CI 0.32, 1.48; p-interaction = 0.67). Conclusions: PAD is associated with continuous and linearly increasing risk for VTE after LER. A strategy of low-dose rivaroxaban plus aspirin versus aspirin alone reduced this risk by 39% with benefits apparent early and continued over time. The addition of clopidogrel does not modify this benefit. VTE, along with arterial thrombotic events, is part of the adverse thrombotic risk profile in PAD patients, and low-dose rivaroxaban plus aspirin provides protection against venous and arterial thrombosis.

Patients with peripheral artery disease (PAD) are at heightened risk for ischemic events related to atherothrombosis. Antithrombotic therapies can reduce the risk of atherothrombotic events but increase bleeding. Importantly, there is growing appreciation of the heterogeneity in risk profile and effect of antithrombotic therapies in different populations, including those with PAD. Further, patients with PAD are at risk for not only major adverse cardiovascular events but also major adverse limb events, and the drivers of risk for each are different. Within PAD populations, data from trials may be difficult to interpret due to differences among the studies with regards to patient population, clinical settings, and outcomes examined. The acute setting of peripheral revascularization which involves plaque rupture and endothelial disruption confers very high risk of major adverse limb events early postprocedure. Among patients with chronic PAD for whom the goal of antithrombotic therapy is secondary prevention, concomitant coronary artery disease, particularly with prior myocardial infarction, is associated with greatest risk for major adverse cardiovascular events, while prior peripheral revascularization or amputation is associated with greatest risk for major adverse limb events. Understanding of the potential impact of clinical setting and patient risk profile is important to guide evidence-based decisions regarding antithrombotic therapy in patients with PAD. In this article, we provide a contemporary review of data supporting the use of antithrombotic therapy in PAD, as well as a clinical framework for analysis and translation of these data into practice, highlighting areas in need of further investigation.

Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of low-density lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia. In addition, adverse effects of statins may limit their tolerability and therefore the ability to attain effective doses in some patients. A new class of drugs that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) has been developed to treat hyperlipidemia. This review discusses the history and mechanism of action of PCSK9 inhibitors, their metabolic effects, and clinical outcomes associated with these medications, highlighting recent large cardiovascular outcome trials investigating these therapies.

Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation.

The objectives of this longitudinal study were to examine differences between whites and blacks, and across two geographical regions, in the socio-demographic, clinical, and psychosocial characteristics, hospital treatment practices, and post-discharge mortality for hospital survivors of an acute coronary syndrome (ACS). In this prospective cohort study, we performed in-person interviews and medical record abstractions for patients discharged from the hospital after an ACS at participating sites in Central Massachusetts and Central Georgia during 2011–2013. Among the 1143 whites in Central Massachusetts, 514 whites in Central Georgia, and 277 blacks in Central Georgia, we observed a gradient of socioeconomic position with whites in Central Massachusetts being the most privileged, followed by whites and then blacks from Central Georgia; similar gradients pertained to psychosocial vulnerability (e.g., 10.7%, 25.1%, and 49.1% had cognitive impairment, respectively) and to the hospital receipt of all 4 evidence-based cardiac medications (35.5%, 18.1%, and 14.4%, respectively) used in the acute management of patients hospitalized with an ACS. Multivariable adjusted odds ratios (95% confidence intervals) for the receipt of a percutaneous coronary intervention for whites and blacks in Georgia vs. whites in Massachusetts were 0.57 (0.46–0.71) and 0.40(0.30–0.52), respectively. Thirty-day and one-year mortality risks exhibited a similar gradient. The results of this contemporary clinical/epidemiologic study in a diverse patient cohort suggest that racial and geographic disparities continue to exist for patients hospitalized with an ACS., Highlights • We observed a gradient of socio-economic position, treatment practices, and dying. • Interplay of race and place with treatment practices and post discharge outcomes. • Racial and geographic disparities continue to exist for patients after an ACS.

Objective Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. Methods We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. Results Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. Conclusions Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.

Background Long-term cardiovascular and limb outcomes after revascularization for peripheral artery disease and, in particular, prognosis after post-procedure major adverse limb events (MALE) are not well-studied. Objectives This study sought to describe outcomes after peripheral revascularization and assess relationships between post-procedure MALE hospitalization and subsequent events. Methods Patients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2015, in the Premier Healthcare Database were examined for the co-primary outcomes of interest, composite myocardial infarction (MI) or stroke and composite major amputation or peripheral revascularization. Multivariable adjusted Cox proportional hazards models with post-procedure MALE hospitalization included as a time-dependent covariate were developed to estimate hazard ratios for outcomes. Results Among 393,017 revascularized patients followed for a median of 2.7 years (interquartile range: 1.3 to 4.4 years), the cumulative incidence of MI or stroke was 9.8% and that of major amputation or peripheral revascularization was 41.9%. A total of 50,750 patients (12.9%) had at least 1 post-procedure MALE hospitalization. In time-dependent covariate adjusted models, post-procedure MALE hospitalization was associated with greater risk of subsequent MI or stroke (hazard ratio: 1.34; 95% confidence interval: 1.28 to 1.40) and major amputation or peripheral revascularization (hazard ratio: 8.13; 95% confidence interval: 7.96 to 8.29). After peripheral revascularization with or without post-procedure MALE hospitalization, risk of limb events increased rapidly post-procedure and more slowly after the first year, whereas cardiac risk increased steadily during follow-up. Conclusions Revascularized peripheral artery disease patients face earlier limb and later cardiovascular ischemic risk that is heightened among patients with post-procedure MALE hospitalization. Increased provider awareness of these long-term risks may guide efforts to improve post-procedural outcomes.

Background: SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women), a randomized controlled trial comparing radial and femoral access in women undergoing cardiac catheterization or percutaneous coronary intervention (PCI), was terminated early for lower than expected event rates. Whether this was because of patient selection or better access site practice among trial patients is unknown. Methods and Results: SAFE-PCI was conducted within the National Cardiovascular Data Registry CathPCI registry. Using the National Cardiovascular Research Infrastructure Identification, PCI date, and age, patients enrolled in SAFE-PCI were compared with trial-eligible female CathPCI registry patients 1 year before, during, and 1 year after SAFE-PCI enrollment. Patient and procedure characteristics, predicted bleeding and mortality, and post-PCI bleeding were compared between groups. Enrolled SAFE-PCI patients and registry patients from the 3 time periods were linked to Centers for Medicare and Medicaid Services data to compare 30-day death and unplanned revascularization rates. At 54 SAFE-PCI sites, there were 496 SAFE-PCI trial patients with a PCI visit within the CathPCI registry. There were 24 958 registry patients from 1 year before and 1 year after SAFE-PCI enrollment and 15 904 trial-eligible registry patients during trial enrollment. Trial patients were younger, had lower predicted bleeding and mortality, and had lower rates of post-PCI bleeding within 72 hours compared with registry patients. Among 12 212 Centers for Medicare and Medicaid Services–linked patients, there were no significant differences in 30-day death and unplanned revascularization among the 4 groups. Conclusions: Lower predicted risk of bleeding and mortality among SAFE-PCI trial patients compared with registry patients suggests that lower-risk patients were selectively enrolled for the trial. These data demonstrate how registry-based randomized trials may offer methods for enrollment feedback to curb selection bias in recruitment. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01406236.

Background: Race and sex disparities in in-hospital treatment and outcomes of patients with acute myocardial infarction (MI) have been described, but little is known about race and sex differences in post-MI angina and long-term risk of unplanned rehospitalization. We examined race and sex differences in post-MI angina frequency and 1-year unplanned rehospitalization to identify factors associated with unplanned rehospitalization, testing for whether race and sex modify these relationships. Methods: Using TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome) data, we examined 6-week and 1-year angina frequency and 1-year unplanned rehospitalization stratified by race and sex among MI patients treated with percutaneous coronary intervention. We used multivariable logistic regression to assess factors associated with unplanned rehospitalization and tested for interactions among angina frequency, race, and sex. Results: A total of 11 595 MI patients survived to 1 year postdischarge; there were 66.6% white male patients, 24.3% white female patients, 5.3% black male patients, and 3.8% black female patients. Overall, 29.7% had angina at 6 weeks, and 20.6% had angina at 1 year postdischarge. Relative to white patients, black patients were more likely to have angina at 6 weeks (female: 44.2% versus 31.8%; male: 33.5% versus 27.1%; both P P P P P interaction =0.41). Conclusions: One-fifth of MI patients treated with percutaneous coronary intervention report 1-year postdischarge angina, with black and female patients more likely to have angina and to be rehospitalized. Better treatment of post-MI angina may improve patient quality of life and quality of care and help to lower rates of rehospitalization overall and particularly among black and female patients, given their high prevalence of post-MI angina. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01088503.

Background Epidemiological studies demonstrating a relationship between gout and cardiovascular disease are older and predate modern cardiovascular preventive therapy. We assessed the contemporary association between gout and cardiovascular disease in patients with obstructive coronary artery disease. Methods and Results Data were from the Duke Databank for Cardiovascular Diseases, which followed up patients undergoing cardiac catheterization with obstructive coronary artery disease at Duke University Medical Center (1998–2013). We assessed the relationship between gout diagnosis at baseline or during follow‐up and the primary composite outcome of cardiovascular death, myocardial infarction, or stroke, adjusting for differences in baseline clinical factors. Secondary end points included cardiovascular death and all‐cause mortality. New, postbaseline, gout diagnosis was included as a time‐dependent covariate. Among 17 201 patients, 1406 (8.2%) had baseline gout and a high burden of cardiovascular risk factors, but high rates of optimal medical therapy. Over a median follow‐up of 6.4 years, gout diagnosis at time of catheterization was not associated with the primary outcome (hazard ratio [95% confidence interval], 1.05 [0.96–1.15]; P =0.31) or cardiovascular death (hazard ratio [95% confidence interval], 1.10 [0.99–1.22]; P =0.08), but was associated with increased all‐cause mortality (hazard ratio [95% confidence interval], 1.13 [1.05–1.23]; P =0.002). After including new, postbaseline, gout diagnosis, the instantaneous risk of the primary outcome was significantly associated with prior gout diagnosis (hazard ratio [95% confidence interval], 1.15 [1.07–1.25]; P =0.0004). Conclusions A clinical history of gout is associated with worse outcomes in a contemporary population of patients with obstructive coronary artery disease. This increased risk exists despite high levels of optimal baseline cardiovascular disease medical therapy, suggesting that residual cardiovascular risk is not addressed by standard medical therapy.

Introduction: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y inhibitors are unclear. Methods and results: We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010–2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P 6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99–1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13–1.59). Conclusion: Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE.

Background— Previous studies examining early readmission after acute myocardial infarction have focused exclusively on inpatient readmissions. However, from a patient’s perspective, any unplanned inpatient or observation rehospitalization after acute myocardial infarction represents a significant event; these unplanned rehospitalizations have not been well characterized. Methods and Results— We examined all patients with acute myocardial infarction treated with percutaneous coronary intervention and discharged alive from 233 hospitals in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Our primary outcome was unplanned rehospitalizations (inpatient or observation status) within 30 days after discharge. We identified factors associated with unplanned rehospitalizations using multivariable logistic regression. Among 12 312 patients, 1326 (10.8%) had 1483 unplanned rehospitalizations within 30 days of the index event: 1028 (69.3%) were inpatient readmissions, and 455 (30.7%) were observation stays. The majority of unplanned rehospitalizations (72%) were for cardiovascular reasons. Variation in hospital rates of 30-day unplanned rehospitalization ranged from 5.4% to 20.0%, with a median of 10.7%. After multivariable modeling, the factors most strongly associated with unplanned rehospitalization were baseline quality of life and depression, followed by index hospital length of stay. Conclusions— Early unplanned rehospitalizations are common after acute myocardial infarction, and close to one third were classified as an observation stay. Predischarge and postdischarge assessments of overall, not just cardiovascular, health and strategies to optimize patient functional status may help to reduce unplanned rehospitalizations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01088503.

Background In the SAFE-PCI for Women trial, patient preference for radial access for future procedures was greater than for femoral access. We sought to assess whether radial or femoral access impacts formal measures of quality-of-life (QOL) among women undergoing cardiac catheterization. Methods We assessed QOL using European quality of life–5 dimensions (EQ-5D) and EQ visual analog scale (EQ-VAS) scores among 304 women randomized to radial or femoral arteriotomy in the SAFE-PCI for Women trial at sites with QOL substudy approval. Patient surveys were administered at baseline, hospital discharge, and 30 days (for percutaneous coronary intervention patients). Results Women randomized to both treatments had similar EQ-5D index and EQ-VAS scores at baseline, hospital discharge, and 30-day follow-up. After adjustment for baseline scores, there was no effect of assigned treatment on EQ-5D (discharge 0.004; 95% CI −0.03 to 0.04; 30 days −0.03; 95% CI −0.09 to 0.02) or EQ-VAS (discharge −1.31; 95% CI −4.74 to 2.12; 30 days −2.10; 95% CI −8.92 to 4.71) scores. At discharge, 60.5% versus 63.5% ( P = .60) of patients in radial and femoral groups were free from access site pain; at 30 days, rates were 85.7% versus 77.6% ( P = .30), respectively. Patient preference for the same access strategy for repeat procedures was greater in the radial versus femoral group (77.2% vs 26.8%; P Conclusions Using established QOL instruments, we did not measure any difference in QOL or functional status according to access site strategy in women undergoing cardiac catheterization, yet patient preference for the radial approach was significantly greater. Other factors influencing patient choice for radial access should be investigated.

Background: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS).Objectives: We investigated whether background concomitant antiplatelet therapy influence...

Background Revascularization is important for symptom treatment and limb salvage in peripheral artery disease, yet little data exist on the incidence of post-procedure major adverse limb events (MALE) and longer-term outcomes. Objectives This study sought to characterize hospitalizations and outpatient endovascular revascularizations after peripheral artery revascularization, assess temporal trends for outcomes, and identify factors associated with subsequent MALE hospitalization. Methods Patients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2014, in the Premier Healthcare Database were examined for the primary outcome of 1-year MALE hospitalization. Secondary outcomes included 1-year outpatient endovascular revascularization and limb-related, cardiovascular, and all-cause inpatient hospitalizations. Multivariable logistic regression was used to identify factors associated with 1-year MALE hospitalization. Results Among 381,415 revascularized patients, within 1 year post-index revascularization, 10.3% (n = 10,182) had a hospitalization for MALE, 11.0% (n = 42,056) had an outpatient endovascular revascularization, 18.8% (n = 71,663) had a limb-related hospitalization, 12.8% (n = 48,875) had a cardiovascular hospitalization, and 38.9% (n = 148,457) had any inpatient hospitalization. Over the study period, limb-related, cardiovascular, and all-cause hospitalizations decreased, whereas rates of outpatient endovascular revascularizations increased. Male sex, black race, Medicare and Medicaid insurance, diabetes, renal insufficiency, heart failure, smoking, baseline critical or acute limb ischemia, surgical revascularization, and noncardiology operator specialty were significantly associated with increased risk of MALE hospitalization. Conclusions In contemporary practice, hospitalization for MALE occurs in 1 in 10 patients within 1 year after peripheral revascularization and is associated with patient and procedural factors. These data may inform efforts to improve post-procedure outcomes and limb-related clinical trial design.

Background Angina has important implications for patients’ quality of life and healthcare utilization. Angina management after acute myocardial infarction ( MI ) treated with percutaneous coronary intervention (PCI) is unknown. Methods and Results TRANSLATE ‐ ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) was a longitudinal study of MI patients treated with percutaneous coronary intervention at 233 US hospitals from 2010 to 2012. Among patients with self‐reported angina at 6 weeks post‐ MI , we described patterns of angina and antianginal medication use through 1 year postdischarge. Of 10 870 percutaneous coronary intervention–treated MI patients, 3190 (29.3%) reported angina symptoms at 6 weeks post‐ MI ; of these, 658 (20.6%) had daily/weekly angina while 2532 (79.4%) had monthly angina. Among patients with 6‐week angina, 2936 (92.0%) received β‐blockers during the 1 year post‐ MI , yet only 743 (23.3%) were treated with other antianginal medications. At 1 year, 1056 patients (33.1%) with 6‐week angina reported persistent angina symptoms. Of these, only 31.2% had been prescribed non–β‐blocker antianginal medications at any time in the past year. Among patients undergoing revascularization during follow‐up, only 25.9% were on ≥1 non–β‐blocker anti‐anginal medication at the time of the procedure. Conclusions Angina is present in one third of percutaneous coronary intervention–treated MI patients as early as 6 weeks after discharge, and many of these patients have persistent angina at 1 year. Non–β‐blocker antianginal medications are infrequently used in these patients, even among those with persistent angina and those undergoing revascularization.

Background Patients receiving oral anticoagulation in addition to dual‐antiplatelet therapy are known to be at high risk for bleeding events; thus, the selection of a drug‐eluting stent (DES) versus a bare metal stent (BMS) can have important implications for patients with atrial fibrillation (AF) presenting with acute myocardial infarction (MI). Methods and Results From the National Cardiovascular Data Registry ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry—Get With the Guidelines, we identified 14 427 AF patients presenting with acute MI undergoing percutaneous coronary intervention from 2008 to 2014. Temporal trends and hospital variation in DES use were examined, as were patterns of use by stroke risk (CHA 2 DS 2 ‐VASc) and bleeding risk ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation). Among patients with linked Medicare data (n=2844), multivariable Cox regression modeling was used to compare risks for a composite outcome (all‐cause mortality, readmission for stroke, or MI), readmission for stroke, revascularization, and major bleeding at 1 year. A DES was used in 8414 (58.9%) MI patients with AF, increasing from 47.1% in 2008 to 67.9% in 2014, with wide variation among hospitals. DES placement was more common than BMS placement among patients at high stroke risk (CHA 2 DS 2 ‐VASc ≥2) and high bleeding risk (ATRIA ≥4). Although aspirin and a P2Y 12 inhibitor were prescribed for >95% of all patients regardless of stent type at discharge, warfarin was prescribed less frequently among patients receiving a DES than a BMS (31% versus 39%, P Conclusions Use of DESs among MI patients with AF has increased over time, but substantial hospital‐level variation was observed. Patients with AF meeting indications for anticoagulation are more likely to receive a DES than a BMS, even among those at high predicted risk of both stroke and bleeding.

Polyvascular disease (PVD) and diabetes mellitus (DM) are additive for the risk of major adverse cardiovascular events (MACE) in patients with coronary disease. Whether this risk relationship for MACE as well as for amputation is also true in symptomatic peripheral artery disease (PAD) is not well

Peripheral artery disease (PAD) and diabetes mellitus (DM) are each associated with heightened ischemic risk and large economic burden. Whether the risks and costs are further heightened in patients with both PAD and DM is not well described. Patients undergoing peripheral revascularization with

More potent anti-thrombotic strategies have been shown to reduce major adverse limb events (MALE) in patients with atherosclerosis. Ticagrelor is a potent P2Y12 inhibitor that reduces major adverse cardiovascular events (MACE) in stable patients with prior myocardial infarction and in those with