Publications by Year: 2021

BACKGROUND The long-term safety of paclitaxel-coated devices (PCDs; drug-coated balloon or drug-eluting stent) for peripheral endovascular intervention is uncertain. We used data from the Veterans Health Administration to evaluate the association between PCDs, long-term mortality, and cause of death. METHODS AND RESULTS Using the Veterans Administration Corporate Data Warehouse in conjunction with International Classification of Diseases, Tenth Revision (ICD-10) Procedure Coding System, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes, we identified patients with peripheral artery disease treated within the Veterans Administration for femoropopliteal artery revascularization between October 1, 2015, and June 30, 2019. An adjusted Cox regression, using stabilized inverse probability-weighted estimates, was used to evaluate the association between PCDs and long-term survival. Cause of death data were obtained using the National Death Index. In total, 10 505 patients underwent femoropopliteal peripheral endovascular intervention; 2265 (21.6%) with a PCD and 8240 (78.4%) with a non-PCD (percutaneous angioplasty balloon and/or bare metal stent). Survival rates at 2 years (77.4% versus 79.7%) and 3 years (70.7% versus 71.8%) were similar between PCD and non-PCD groups, respectively. The adjusted hazard for all-cause mortality for patients treated with a PCD versus non-PCD was 1.06 (95% CI, 0.95-1.18, P=0.3013). Among patients who died between October 1, 2015, and December 31, 2017, the cause of death according to treatment group, PCD versus non-PCD, was similar. CONCLUSIONS Among patients undergoing femoropopliteal peripheral endovascular intervention within the Veterans Administration Health Administration, there was no increased risk of long-term, all-cause mortality associated with PCD use. Cause-specific mortality rates were similar between treatment groups.

Peripheral artery disease (PAD) is a common condition with increasing prevalence domestically and worldwide. Patients with PAD have a poor prognosis, as PAD is associated with high rates of myocardial infarction, ischemic stroke, and cardiovascular disease death. The primary symptom of PAD, claudication, significantly reduces quality of life and functional status and is associated with depression. In addition to several advances in medications for PAD over the last decade, endovascular device therapy has seen a significant breakthrough in the form of paclitaxel-coated devices (PCDs), which significantly reduce rates of restenosis relative to non-PCDs, a finding which has been demonstrated in numerous randomized clinical trials. After their introduction to the market in 2012 (paclitaxel-eluting stents) and 2014 (paclitaxel-coated balloons) their use surged as they replaced non-PCDs and were designated the first-line endovascular therapy by society guidelines. This trend was abruptly reversed, however, after a meta-analysis of summary-level data was published in December of 2018 that reported an elevated mortality associated with PCDs compared with non-PCDs 2-5 years after treatment. This meta-analysis has been criticized for considerable methodological flaws. The Food and Drug Administration conducted a review and concluded that insufficient data existed to make a definitive statement regarding the safety of PCDs. They called for restriction of the use of PCDs to the highest-risk patient populations. At the same time, the FDA deemed pursuing new RCTs to better evaluate PCDs unfeasible due to the high numbers of patients and long follow-up time that would be required. In this setting, real-world data emerged as a powerful source of information for the evaluation of PCDs. Real-world data offers advantages over randomized-controlled trials including expeditious access to and analysis of data and the availability of large numbers of patients. Several retrospective observational studies demonstrate no difference in long-term all-cause mortality in patients treated with PCDs relative to those treated with non-PCDs. This paclitaxel controversy has illustrated the critical role that real-world data is assuming in long-term safety monitoring of medical devices.

BACKGROUND: The presence of a contralateral carotid occlusion (CCO) is an established high-risk feature for patients undergoing carotid endarterectomy (CEA) and is traditionally an indication for carotid artery stenting (CAS). Recent observational data have called into question whether CCO remains a high-risk feature for CEA.

OBJECTIVES: The purpose of this study was to determine the clinical impact of CCO among patients undergoing CEA and CAS in a contemporary nationwide registry.

METHODS: All patients undergoing CEA or CAS from 2007 to 2019 in the NCDR CARE (National Cardiovascular Data Registry Carotid Artery Revascularization and Endarterectomy) and PVI (Peripheral Vascular Intervention) registries were included. The primary exposure was the presence of CCO. The outcome was a composite of in-hospital death, stroke, and myocardial infarction. Multivariable logistic regression and inverse-probability of treatment weighting were used to compare outcomes.

RESULTS: Among 58,423 patients who underwent carotid revascularization, 4,624 (7.9%) had a CCO. Of those, 68.9% (n = 3,185) underwent CAS and 31.1% (n = 1,439) underwent CEA. The average age of patients with CCO was 69.5 ± 9.7 years, 32.6% were women, 92.8% were Caucasian, 51.7% had a prior transient ischemic attack or stroke, and 45.4% presented with symptomatic disease. Over the study period, there was a 41.7% decrease in the prevalence of CCO among patients who underwent carotid revascularization (p < 0.001), but CAS remained the primary revascularization strategy. Unadjusted composite outcome rates were lower in patients with CCO after CAS (2.1%) than CEA (3.6%). Following adjustment, CCO was associated with a 71% increase in the odds of an adverse outcome after CEA (95% confidence interval: 1.27 to 2.30; p < 0.001) compared with no increase after CAS (adjusted odds ratio: 0.94; 95% confidence interval: 0.72 to 1.22; p = 0.64).

CONCLUSIONS: CCO remains an important predictor of increased risk among patients undergoing CEA, but not CAS.

BACKGROUND: The dual antiplatelet therapy (DAPT) score, one of the first prediction tools to attempt to uncouple bleeding and ischemic risk following percutaneous coronary intervention, can help guide antiplatelet duration after coronary intervention. Evaluating the generalizability of the score is important to understand its utility in clinical practice.

METHODS: We conducted a systematic review and meta-analysis of studies that validated the DAPT score. A random effect meta-analysis was performed of ischemic and bleeding risk based on DAPT score. A secondary analysis assessed the risk of longer versus shorter P2Y12 inhibitor duration on ischemic and bleeding risk in randomized controlled trials of DAPT duration.

RESULTS: We identified 10 patient cohorts involving 88,563 patients. Compared with a low DAPT score, a high DAPT score was associated with increased ischemic risk (RR: 1.62, 95% CI: 1.41-1.87) and reduced bleeding risk (RR: 0.80, 95% CI: 0.70-0.92). In three randomized trials of DAPT duration that contained information on the DAPT score, the relative risk of net adverse clinical events (combined ischemic and bleeding events) with longer duration of DAPT was 1.56 (95% CI: 0.77-3.19) for low DAPT score patients, and 0.86 (95% CI: 0.61-1.21) for high DAPT score patients (pinteraction = .14).

CONCLUSIONS: In this large meta-analysis, the DAPT score consistently stratified bleeding and ischemic risk in opposing directions across several different study populations. More evaluation is needed to understand if the effect of longer DAPT duration on NACE is modified by the DAPT score in current practice.

BACKGROUND: The connection between paclitaxel-coated devices (PCD) use during peripheral vascular interventions (PVI) and mortality is debated. We aimed to analyze patterns of PCD use and the safety and effectiveness of PCD use in the superficial femoral and/or popliteal arteries.

METHODS: Patients undergoing PVI of femoropopliteal lesions with and without PCD between January 1, 2015 and June 30, 2017 were compared using the American College of Cardiology's National Cardiovascular Data Registry PVI Registry. Outcomes were derived from Centers for Medicare & Medicaid claims data. The primary outcome was all-cause mortality at 6-, 12-, and 24-months following PVI. Inverse probability weighting and frailty models were used to assess the differences between groups. The analysis was IRB-approved.

RESULTS: In the overall cohort consisting of 6,302 femoropopliteal PVIs, PCD-PVI patients were more likely to be treated for claudication (63.5% vs 51.3%, P< .001), less likely to have a chronic total occlusion (24.6% vs 34.7%, P < .001), and more likely to be treated in certain geographic and practice settings. In the analytic cohort consisting of 1,666 femoropopliteal PVIs with linked claims outcomes (888 PCD-PVI, 53.3%), unadjusted rates of all outcomes were lower in PCD-PVI patients. After adjustment, there were no significant differences in mortality following PCD-PVI versus non-PCD PVI at 1 year (adjusted RR 0.78, 95% CI 0.60-1.01, P= .055) or 2 years (aRR 0.98, 95% CI 0.77-1.24, P= .844).

CONCLUSION: There were significant differences between the patients in whom and settings in which PCD-PVI was versus was not used. PCD-PVI was not associated with an increased risk of 2-year mortality in real-world use.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is a common, debilitating disease that impacts 8.5 million Americans and carries a poor prognosis. The most common manifestation of lower extremity PAD is claudication-a condition which significantly reduces quality of life and functional status. Paclitaxel-coated balloons and stents (PCBs and PESs) represented a breakthrough in the ability to treat medication-refractory patients relative to bare metal stents (BMSs) and percutaneous transluminal angioplasty (PTA) because they improve primary patency rates, reduce target lesion revascularization (TLR), and minimize late-lumen loss for femoropopliteal lesions. As a result, paclitaxel-coated devices (PCDs) were swiftly established as the standard of care for revascularization of femoropopliteal artery disease. A recent meta-analysis of summary-level data demonstrated a late mortality signal for patients treated with paclitaxel-coated devices relative to uncoated devices. This has had a major impact on the vascular community and for the treatment of patients with PAD. Herein, we provide a detailed review of the available data on the late mortality signal associated with paclitaxel.

RECENT FINDINGS: In December of 2018, Katsanos et al. J Am Heart Assoc 7: e011245, 2018) published data from randomized-controlled trials (RCTs) that demonstrated an increase in mortality at 2 and 5 years in patients treated with PCDs involving the femoropopliteal arterial segment relative to patients treated with uncoated devices. As a result of this analysis, randomized trials were stopped and the FDA sent a letter to healthcare providers recommending restriction of use of these devices to patients at the highest risk of restenosis. As additional data emerged supporting the safety of these devices, the FDA organized an advisory committee meeting to review the available data and to determine a pathway forward. The FDA concluded that there were insufficient data to make a final decision regarding the safety of PCDs. They allowed these devices to remain on the market, but with revised safety labeling and updated their letter to healthcare providers to continue to restrict use to patients at highest risk of reintervention. The FDA also called for additional long-term data, including from RCTs and real-world data. To date, an updated patient-level meta-analysis of clinical trial data, RCTs with longer-term follow-up, and large observational studies have been conducted. While meta-analyses conducted using overlapping clinical trial data have found a persistent increase in mortality for those treated with PCDs, individual industry-sponsored RCTs and large observational studies have consistently failed to detect a corresponding mortality increase. To date, no mechanism linking paclitaxel to mortality has been observed. We are currently at an impasse for drawing definitive conclusions regarding the long-term safety of paclitaxel-coated devices. As we await enrollment in ongoing clinical trials, we must proceed with making reasonable decisions for our patients' care from the available data, as these devices have important clinical implications for our patients. A critical lesson that can be learned from this controversy is that, for future device trials, committing to long-term follow-up is crucial.

Background It is unknown whether clinical events identified with administrative claims have similar prognosis compared with trial-adjudicated events in cardiovascular clinical trials. We compared the prognostic significance of claims-based end points in context of trial-adjudicated end points in the DAPT (Dual Antiplatelet Therapy) study. Methods and Results We matched 1336 patients aged ≥65 years who received percutaneous coronary intervention in the DAPT study with the CathPCI registry linked to Medicare claims. We compared death at 21 months post-randomization using Cox proportional hazards models among patients with ischemic events (myocardial infarction or stroke) and bleeding events identified by: (1) both trial adjudication and claims; (2) trial adjudication only; and (3) claims only. A total of 47 patients (3.5%) had ischemic events identified by both trial adjudication and claims, 24 (1.8%) in trial adjudication only, 15 (1.1%) in claims only, and 1250 (93.6%) had no ischemic events, with annualized unadjusted mortality rates of 12.8, 5.5, 14.9, and 1.26 per 100 person-years, respectively. A total of 44 patients (3.3%) had bleeding events identified with both trial adjudication and claims, 13 (1.0%) in trial adjudication only, 65 (4.9%) in claims only, and 1214 (90.9%) had no bleeding events, with annualized unadjusted mortality rates of 11.0, 16.8, 10.7, and 0.95 per 100 person-years, respectively. Among patients with no trial-adjudicated events, patients with events in claims only had a high subsequent adjusted mortality risk (hazard ratio (HR) ischemic events: 31.5; 95% CI, 8.9‒111.9; HR bleeding events 23.9; 95% CI, 10.7‒53.2). Conclusions In addition to trial-adjudicated events, claims identified additional clinically meaningful ischemic and bleeding events that were prognostically significant for death.

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD).

MATERIALS AND METHODS: The LIBERTY trial (ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory-assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling.

RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients.

CONCLUSION: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

PURPOSE: To examine nationwide variations in inpatient use of drug-coated balloons (DCBs) for treating femoropopliteal segment occlusive disease and whether DCBs are associated with reduced early out-of-hospital health care utilization.

MATERIALS AND METHODS: The study included 24,022 patients who survived hospitalization for femoropopliteal revascularization using DCB angioplasty (n=7850) or uncoated balloon angioplasty (n=16,172) in the 2016-2017 Nationwide Readmissions Database. Differences in patient, hospitalization, and institutional characteristics were compared between treatment strategies. Adjusted logistic regression models were used to examine differences in 6-month rates of readmission, amputation, and repeat intervention. Results are presented as the odds ratio (OR) and 95% confidence interval (CI).

RESULTS: Patients treated with DCBs had a higher prevalence of chronic limb-threatening ischemia, diabetes, hypertension, and tobacco use. Revascularization with a DCB was associated with shorter hospitalizations, lower median hospitalization costs, and fewer inpatient lower extremity amputations. Readmissions at 6 months were decreased in patients treated with DCBs compared with uncoated balloon angioplasty (OR 0.90, 95% CI 0.83 to 0.98, p=0.014). The most common reasons for readmission were complications related to procedures (15.4%) and diabetes (15.4%). Compared to patients treated with DCBs, patients treated with uncoated balloon angioplasty were more often readmitted with early procedure-related complications (13.3% vs 17.5%). There were no between-group differences in readmission for sepsis, myocardial infarction, or congestive heart failure.

CONCLUSION: DCBs are less often used compared to uncoated balloons during inpatient femoropopliteal procedures. While DCB utilization is associated with more severe comorbidities and advanced peripheral artery disease, readmission rates are decreased through the first 6 months.

BACKGROUND: Whether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID-19 is uncertain.

OBJECTIVE: To evaluate the impact of HIV infection on COVID-19 outcomes among hospitalized patients.

METHODS: Using the American Heart Association's COVID-19 Cardiovascular Disease registry, we used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics and comorbidities and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS).

RESULTS: The registry included 21,528 hospitalization records of people with confirmed COVID-19 from 107 hospitals in 2020, including 220 people living with HIV (PLWH). PLWH were younger (56.0+/-13.0 versus 61.3+/-17.9 years old) and more likely to be male (72.3% vs 52.7%), Non-Hispanic Black (51.4% vs 25.4%), on Medicaid (44.5% vs 24.5), and active tobacco users (12.7% versus 6.5%).Of the study population, 36 PLWH (16.4%) had in-hospital mortality compared with 3,290 (15.4%) without HIV (Risk ratio 1.06, 95%CI 0.79-1.43; risk difference 0.9%, 95%CI -4.2 to 6.1%; p=0.71). After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.13; 95%CI 0.77-1.6; p 0.54) even after adding body mass index and comorbidities (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91), severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86), or LOS (aOR 1.03; 95% CI 0.76-1.66, p=0.21).

CONCLUSION: HIV was not associated with adverse outcomes of COVID-19 including in-hospital mortality, MACE, or severity of illness.

CONDENSED ABSTRACT: We studied 21,528 patients hospitalized with COVID-19 at 107 hospitals in AHA's COVID-19 registry to examine the association between HIV and COVID-19 outcomes. More patients with HIV were younger, male, non-Hispanic Black, on Medicaid and current smokers. HIV was not associated with worse COVID-19 in-hospital mortality (Risk ratio 1.06, 95%CI 0.79-1.43; p=0.71) even after adjustment (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was also not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91) or severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86. Our findings do not support that HIV is a major risk factor for adverse COVID-19 outcomes.