Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease

BackgroundPatients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.ObjectivesThe 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.MethodsCox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.ResultsEUCLID 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.ConclusionsAlthough 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)     

Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease

BackgroundLow-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.ObjectivesThe authors examined LLT use and actual achieved LDL-C in PAD.MethodsPAD 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-C <70 mg/dl were identified with multivariable logistic regression.ResultsAmong 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.ConclusionsIn 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.     

Impact of High Lipoprotein(a) Levels on Clinical Outcomes Following Peripheral Endovascular Therapy

BackgroundElevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD). However, their prognostic impact in patients with PAD remains unknown.ObjectivesThe aim of this study was to examine the prognostic impact of elevated Lp(a) levels in patients with PAD undergoing endovascular therapy (EVT).MethodsIn total, 1,169 patients who underwent successful EVT for symptomatic PAD between September 2016 and August 2021 were included in this study. High Lp(a) levels were defined as >30 mg/dL. The associations of high Lp(a) levels with incident major adverse cardiovascular events (MACE) (all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE) (repeat revascularization for target limb and major amputation) were analyzed.ResultsDuring a median follow-up period of 1.7 years (IQR: 0.6-3.0 years), 230 MACE (210 deaths, 15 myocardial infarctions, and 22 strokes) and 263 MALE (219 reinterventions and 36 major amputations) were observed. The cumulative incidence rate of MACE (48.1% vs 27.3%) and MALE (67.9% vs 27.2%) was significantly higher in patients with high Lp(a) levels (P < 0.001 for both). The adjusted HR were 1.93 (95% CI: 1.44-2.59; P < 0.001) for MACE and 4.15 (95% CI: 3.14-5.50; P < 0.001) for MALE. These associations were not influenced by low-density lipoprotein cholesterol levels or statin administration (P for interaction >0.05 for all).ConclusionsElevated Lp(a) levels were independently associated with incident MACE and MALE in patients with PAD treated with revascularization irrespective of low-density lipoprotein cholesterol level and statin administration.     

Revascularization Strategies for Patients With Femoropopliteal Peripheral Artery Disease

BackgroundNo adequately powered studies exist to compare major clinical outcomes after endovascular therapy (EVT) with stent implantation vs bypass surgery (BSx) for symptomatic femoropopliteal peripheral artery disease.ObjectivesThis study sought to perform a pooled analysis of individual patient data from all randomized controlled trials comparing EVT vs BSx.MethodsPrincipal investigators of 5 of 6 available randomized controlled trials agreed to pool individual patient data. The primary endpoint was major adverse limb events, a composite of all-cause death, major amputation, or target limb reintervention. Secondary endpoints included amputation-free survival, individual major adverse limb event components, and primary patency. Early complications were bleeding, infection, or all-cause death within 30 days.ResultsA total of 639 patients were analyzed with a mean age of 68.1 ± 9.1 years and 29.0% women. Baseline characteristics were comparable between groups. At 2 years, there were no significant differences between patients who received EVT and those who received BSx regarding major adverse limb events (40.1% vs 36.4%; log-rank P = 0.447; adjusted HR [aHR]: 1.04; 95% CI: 0.80-1.36), amputation-free survival (88.1% vs 90.0%; log-rank P = 0.455; aHR for death or amputation: 1.04; 95% CI: 0.63-1.71) and the other secondary endpoints except for primary patency, which was lower in patients who received EVT vs those who received BSx (51.2% vs 61.3%; log-rank P = 0.024; aHR for loss of primary patency: 1.31; 95% CI: 1.02-1.69). EVT was associated with significantly lower rates of early complications (6.8% vs 22.6%; P < 0.001) and shorter hospital stay (3.1 ± 4.2 days vs 7.4 ± 4.9 days; P < 0.001).ConclusionsThese findings further support the efficacy and safety of EVT as an alternative to BSx in patients with symptomatic femoropopliteal peripheral artery disease.     

Nonculprit Lesion Myocardial Infarction Following Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome

BackgroundRecent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients.ObjectivesThe authors sought to examine the effect of more potent antiplatelet therapy on the basis of the timing and etiology of recurrent myocardial infarction (MI) or cardiovascular death following PCI for ACS.MethodsIn the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38), which randomized patients to prasugrel or clopidogrel, 12,844 patients with ACS received at least 1 stent. MI and cardiovascular death were categorized as: 1) procedural (related to revascularization); 2) definite or probable stent thrombosis (ST); or 3) spontaneous (non-ST or non–procedure-related). Median follow-up was 14.5 months.ResultsAmong the first events occurring within 30 days, 584 (69.0%) were procedural, 126 (14.9%) ST-related, and 136 (16.1%) spontaneous. After 30 days, 22 (4.7%) were procedural, 63 (13.5%) were ST-related, and 383 (81.8%) spontaneous. Prasugrel significantly reduced the incidence of MI or cardiovascular death for ST-related (1.0% vs. 2.1%; p < 0.001) and spontaneous events (3.9% vs. 4.8%; p = 0.012), with a directionally consistent numerical reduction for procedural events (4.4% vs. 5.1%; p = 0.078). Prasugrel increased spontaneous, but not procedural, major bleeding.ConclusionsLong-term potent antithrombotic therapy reduces de novo (spontaneous) atherothrombotic events in addition to preventing complications associated with stenting of the culprit lesion following ACS. In patients undergoing PCI for ACS, spontaneous events predominate after 30 days, with the later-phase cardiovascular benefit of potent dual antiplatelet therapy driven largely by reducing de novo atherothrombotic ischemic events. (Comparison of Prasugrel [CS-747] and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591)     

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Randomized Disrupt PAD III Trial

ObjectivesThe study sought to compare short-term outcomes in patients with femoropopliteal artery calcification receiving vessel preparation with intravascular lithotripsy (IVL) or percutaneous transluminal angioplasty (PTA) prior to drug-coated balloon (DCB) for symptomatic peripheral artery disease.BackgroundEndovascular treatment of calcified peripheral artery lesions is associated with suboptimal vessel expansion and increased complication risk. Although initial results from single-arm studies with IVL have been reported, comparative evidence from randomized trials is lacking for most devices in the presence of heavy calcification.MethodsThe Disrupt PAD III (Shockwave Medical Peripheral Lithoplasty System Study for PAD) randomized trial enrolled patients with moderate or severe calcification in a femoropopliteal artery who underwent vessel preparation with IVL or PTA prior to DCB or stenting. The primary endpoint was core lab–adjudicated procedural success (residual stenosis ≤30% without flow-limiting dissection) prior to DCB or stenting.ResultsIn patients receiving IVL (n = 153) or PTA (n = 153), procedural success was greater in the IVL group (65.8% vs. 50.4%; p = 0.01) and the percentage of lesions with residual stenosis ≤30% (66.4% vs. 51.9%; p = 0.02) was greater in the IVL group, while flow-limiting dissections occurred more frequently in the PTA group (1.4% vs. 6.8%; p = 0.03). Post-dilatation (5.2% vs. 17.0%; p = 0.001) and stent placement (4.6% vs. 18.3%; p < 0.001) were also greater in the PTA group. The rates of major adverse events (IVL: 0% vs. PTA: 1.3%; p = 0.16) and clinically driven target lesion revascularization (IVL: 0.7% vs. PTA: 0.7%; p = 1.0) at 30 days were comparable between groups.ConclusionsIVL is an effective vessel preparation strategy that facilitates definitive endovascular treatment in calcified femoropopliteal arteries in patients with peripheral artery disease. (Shockwave Medical Peripheral Lithoplasty System Study for PAD [Disrupt PAD III]; NCT02923193)     

1-Month Dual-Antiplatelet Therapy Followed by Aspirin Monotherapy After Polymer-Free Drug-Coated Stent Implantation: One-Month DAPT Trial

ObjectivesThe aim of this study was to determine whether 1 month of dual-antiplatelet therapy (DAPT) followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation is noninferior to 6 to 12 months of DAPT after biodegradable-polymer drug-eluting stent (BP-DES) implantation.BackgroundIt is necessary to determine the optimal minimal duration of DAPT followed by aspirin monotherapy after percutaneous coronary intervention (PCI).MethodsIn this trial, 3,020 patients with coronary artery disease considered for PCI for noncomplex lesions were randomized to 1-month DAPT after PF-DCS (n = 1,507) or 6- to 12-month DAPT after BP-DES (n = 1,513). The primary endpoint was the 1-year composite of cardiac death, nonfatal myocardial infarction, target vessel revascularization, stroke, or major bleeding (noninferiority hypothesis margin of 3%).ResultsThe primary endpoint occurred in 88 patients (5.9%) in the 1-month DAPT after PF-DCS group and 98 patients (6.5%) in the 6- to 12-month DAPT after BP-DES group (absolute difference −0.7%; upper limit of 1-sided 97.5% confidence interval: 1.33%; P < 0.001 for noninferiority). The occurrence of major bleeding was not different (1.7% vs 2.5%; P = 0.136). There was no difference in the occurrence of stent thrombosis (0.7% vs 0.8%; P = 0.842).ConclusionsAmong patients who underwent PCI for noncomplex lesions, 1-month DAPT followed by aspirin monotherapy after PF-DCS implantation was noninferior to 6- to 12-month DAPT after BP-DES implantation for the 1-year composite of cardiovascular events or major bleeding. The present findings need to be interpreted in the setting of different types of stents according to antiplatelet strategy. (A Randomized Controlled Comparison Between One Versus More Than Six Months of Dual Antiplatelet Therapy After Biolimus A9-Eluting Stent Implantation; NCT02513810)     

Cancer Patients Have a Higher Risk of Thrombotic and Ischemic Events After Percutaneous Coronary Intervention

ObjectivesThis study sought to define the risk of stent thrombosis (ST) and myocardial infarction (MI) in cancer patients compared with noncancer patients after percutaneous coronary intervention (PCI).BackgroundCancer patients are considered to be at high thrombotic risk, but data on whether this is the case after PCI remain inconclusive.MethodsCancer patients undergoing PCI at Mayo Clinic Rochester from January 1, 2003, to December 31, 2013, were identified by cross-linking institutional cancer and PCI databases and by propensity score matching to noncancer patients. The combined primary endpoint was all-cause mortality, MI, and revascularization rate at 5-year follow-up. Secondary endpoints were the individual primary endpoint components, cause of mortality, ST, and Bleeding Academic Research Consortium 2+ bleeding.ResultsThe primary endpoint occurred in 48.6% of 416 cancer and in 33.0% of 768 noncancer patients (p < 0.001). In competing risk analyses, cancer patients had a higher rate of noncardiac death (24.0% vs. 10.5%; p < 0.001) and a lower rate of cardiac death (5.0% vs. 11.7%; p < 0.001). Cancer patients had a higher rate of MI (16.1% vs. 8.0%; p < 0.001), ST (6.0% vs. 2.3%; p < 0.001), repeat revascularization (21.2% vs. 10.0%; p < 0.001), and bleeding (6.7% vs. 3.9%; p = 0.03). The most critical period for ST in cancer patients was in the first year after PCI. The dual antiplatelet therapy score was predictive of thrombotic and ischemic events in both groups.ConclusionsCancer patients have a higher risk of thrombotic and ischemic events after PCI, identifiable by a high dual antiplatelet therapy score. These findings have important implications for antiplatelet therapy decisions.     

Real-World Experience With a Paclitaxel-Coated Balloon in Critical Limb Ischemia: 24-Month Subgroup Outcomes of BIOLUX P-III

ObjectivesThe aim of the BIOLUX P-III (A Prospective, International, Multi-Centre, Post-Market All-Comers Registry to Assess the Clinical Performance of the Passeo-18 Lux Paclitaxel Releasing Balloon Catheter in Infrainguinal Arteries – III) registry was to collect real-world data on the Passeo-18 Lux paclitaxel-coated balloon.BackgroundCritical limb ischemia (CLI) is a severe condition associated with high morbidity and mortality. Prospective data are needed to provide further insights on drug-eluting devices.MethodsBIOLUX P-III is a prospective, post-market, all-comers registry assessing the safety and performance of the Passeo-18 Lux. Clinical information was collected at 6, 12, and 24 months. The authors report 24-month outcomes of the CLI subgroup with patients in Rutherford classes 4 to 6.ResultsThe CLI subgroup included 328 patients with 422 lesions. Patients were 71.1 ± 10.5 years of age, and 61.0% had diabetes. Femoropopliteal lesions were present in 53.8% (n = 227), below-the-knee lesions were present in 27.0% (n = 114), and lesions were moderate or heavily calcified in 45.0% (n = 190). Major adverse events, defined as 30-day device- or procedure-related mortality, major target limb amputation, and clinically driven target lesion revascularization, occurred in 9.8% of patients through 6 months, in 14.9% through 12 months, and in 19.4% through 24 months. Clinically driven target lesion revascularization occurred in 4.4%, 8.5%, and 12.1%, major amputation in 4.9%, 5.2%, and 6.1%, and mortality in 8.1%, 11.1%, and 20.1%, respectively. Predictors of mortality were age ≥75 years and higher Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class, and higher Rutherford class was associated with increased mortality and amputation rates.ConclusionsIn a large, multimorbid patient population with complex lesions and CLI, the safety and performance of the Passeo-18 Lux paclitaxel-coated balloon has been confirmed, with low rates of major amputation and target lesion revascularization.     

Comparison of Drug-Coated Balloons vs Bare-Metal Stents in Patients With Femoropopliteal Arterial Disease

BackgroundEndovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS).ObjectivesThe purpose of this study was to compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials.MethodsPatient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE).ResultsThe primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P < 0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months.ConclusionsIn a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis vs BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.     

Impact of Hospital Procedural Volume on Outcomes After Endovascular Revascularization for Critical Limb Ischemia

ObjectivesThe aim of this study was to evaluate the interaction between hospital endovascular lower extremity revascularization (eLER) volume and outcomes after eLER for critical limb ischemia (CLI).BackgroundThere is a paucity of data on the relationship between hospital procedural volume and outcomes of eLER for CLI.MethodsThe authors queried the Nationwide Readmission Database (2013-2015) for hospitalized patients who underwent eLER for CLI. Hospitals were divided into tertiles according to annual eLER volume: low volume (<100 eLER procedures), moderate volume (100-550 eLER procedures), and high volume (>550 eLER procedures). Stepwise multivariable regression models were used. The main outcomes were in-hospital mortality and 30-day readmission with major adverse limb events, defined as the composite of amputation, acute limb ischemia, or repeat revascularization.ResultsAmong 145,785 hospitalizations for eLER for CLI, 5,199 (3.6%) were at low-volume eLER hospitals, 27,857 (19.1%) at moderate-volume eLER hospitals, and 112,728 (77.3%) at high-volume eLER hospitals. On multivariable analysis, there was no difference with regard to in-hospital mortality among moderate-volume hospitals (adjusted odds ratio [OR]: 0.78; 95% CI: 0.60-1.01) and high-volume hospitals (adjusted OR: 0.84; 95% CI: 0.64-1.05) compared with low-volume hospitals. There was lower risk of in-hospital major amputation (adjusted OR: 0.82; 95% CI: 0.70-0.96) and minor amputation at high- versus low-volume hospitals. The length of hospital stay was shorter and discharges to nursing facilities were fewer among moderate- and high-volume hospitals compared with low-volume hospitals. Compared with low-volume hospitals, eLER for CLI at high-volume hospitals had a lower risk for 30-day readmission with major adverse limb events (adjusted OR: 0.83; 95% CI: 0.70-0.99), while there was no difference among moderate-volume hospitals (adjusted OR: 0.92; 95% CI: 0.77-1.10).ConclusionsThis nationwide observational analysis suggests that annual eLER volume does not influence in-hospital mortality after eLER for CLI. However, high eLER volume (>550 eLER procedures) was associated with better rates of limb preservation after eLER for CLI.     

Simultaneous Hybrid Coronary Revascularization vs Conventional Strategies for Multivessel Coronary Artery Disease: A 10-Year Follow-Up

BackgroundAlthough evidence is sufficient to confirm that hybrid coronary revascularization (HCR) is safe and effective in the short term, its value in the long run is debatable.ObjectivesThis study sought to compare the long-term outcomes of HCR with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multivessel disease.MethodsThree groups of patients, 540 each, receiving HCR, CABG, or PCI between June 2007 to September 2018, were matched using propensity score matching. Patients were stratified by EuroSCORE (European System for Cardiac Operative Risk Evaluation) II (low ≤0.9; 0.9 < medium <1.5; high ≥1.5) and SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (low ≤22; 22 < medium <33; high ≥33). Major adverse cardiac and cerebrovascular events (MACCE) and Seattle Angina Questionnaire (SAQ) scores were compared among the 3 groups.ResultsIn terms of MACCE and SAQ, HCR performed similarly to off-pump CABG but significantly outperformed PCI (P < 0.001). In the low-to-medium EuroSCORE II and medium-to-high SYNTAX score tertiles, MACCE rates in the HCR group were significantly lower than those in the PCI (EuroSCORE II: low, 30.7% vs 41.2%; P = 0.006; medium, 31.3% vs 41.7%; P = 0.013; SYNTAX score: medium, 27.6% vs 41.2%; P = 0.018; high, 32.4% vs 52.7%; P = 0.011) but were similar to those in the CABG group. In the high EuroSCORE II stratum, HCR had a lower MACCE rate than CABG (31.9% vs 47.0%; P = 0.041) and PCI (31.9% vs 53.7%; P = 0.015).ConclusionsCompared with conventional strategies, HCR provided satisfactory long-term outcomes in MACCE and functional status for multivessel disease.     

Randomized Controlled Trial of Acotec Drug-Eluting Balloon Versus Plain Balloon for Below-the-Knee Angioplasty

ObjectivesThe aim of this study was to investigate the efficacy and safety of the Litos drug-coated balloon (DCB) versus plain old balloon angioplasty (POBA) for reduction of late lumen loss (LLL) in patients with critical limb ischemia undergoing below-the-knee (BTK) intervention.BackgroundRestenosis after balloon angioplasty of BTK arteries approximates 70%. Previous studies of DCBs in BTK arteries produced conflicting results.MethodsACOART-BTK (Evaluation of the Use of ACOTEC Drug-Eluting Balloon Litos® in Below-the-Knee Arteries to Treat Critical Limb Ischemia) is a randomized controlled single-center study. Inclusion criteria were critical limb ischemia (Rutherford class ≥4) and significant stenosis or occlusion >40 mm of at least 1 BTK vessel with distal runoff successfully treated with angioplasty. Six-month angiographic LLL was the primary endpoint. Occlusive restenosis at 6 months and clinically driven target lesion revascularization at 12 months were secondary endpoints.ResultsFrom January 2016 through January 2019, 105 patients with 129 BTK lesions were enrolled in the study. Mean lesion length was 168 ± 109 mm in the DCB group and 187 ± 113 mm in the POBA group (p = 0.30). Almost 70% of lesions were occluded at baseline in both groups. On 6-month angiography, mean LLL was 0.51 ± 0.60 mm in the DCB group and 1.31 ± 0.72 mm in the POBA group (p < 0.001); rates of occlusive restenosis were 8.6% and 48.4%, respectively (p < 0.001). Twelve-month clinically driven target lesion revascularization occurred in 6 of 62 DCB-treated lesions (10%) versus 27 of 66 POBA-treated lesions (41%) (p < 0.001). Complete healing at 12 months was observed in 42 of 47 DCB-treated limbs (89.4) versus 35 of 47 POBA-treated limbs (74.5%) (p = 0.05); no major amputations occurred.ConclusionsLitos DCBs strikingly reduced LLL, vessel reocclusion, and clinically driven target lesion revascularization compared with POBA in BTK angioplasty.     

Effect of Calcium-Channel Blocker Therapy on Radial Artery Grafts After Coronary Bypass Surgery

BackgroundFew studies have evaluated the effect of chronic calcium-channel blocker therapy (CCB) on the angiographic and clinical outcome of radial artery (RA) grafts used for coronary bypass surgery.ObjectivesThe purpose of this study was to evaluate if CCB influences midterm clinical and angiographic outcomes of RA grafts.MethodsPatient-level data of 6 angiographic randomized trials evaluating RA graft status at midterm follow-up were joined in this observational analysis. Cox regression and propensity score methods were used to evaluate the effect of CCB on the incidence of a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and repeat revascularization) and graft occlusion.ResultsThe study population included 732 patients (502 on CCB). The median clinical follow-up was 60 months. The cumulative incidence of MACE at 36, 72, and 108 months was 3.7% vs. 9.3%, 13.4% vs. 17.6%, and 16.8% vs. 20.5% in the CCB and no CCB groups, respectively (log-rank p = 0.003). Protocol-driven angiographic follow-up was available in 243 patients in the CCB group and 200 in the no CCB group. The median angiographic follow-up was 55 months. The cumulative incidence of RA occlusion at 36, 72, and 108 months was 0.9% vs. 8.6%, 9.6% vs. 21.4%, and 14.3% vs. 38.9% in the CCB and no CCB groups, respectively (log-rank p < 0.001). After controlling for known confounding, CCB therapy was found to be consistently associated with a significantly lower risk of MACE (multivariate Cox hazard ratio: 0.52; 95% confidence interval: 0.31 to 0.89; p = 0.02) and RA graft occlusion (multivariate Cox hazard ratio: 0.20; 95% confidence interval: 0.08 to 0.49; p < 0.001).ConclusionsIn patients with RA grafts CCB is associated with significantly better midterm clinical and angiographic RA outcomes.     

Impact of Pulmonary Artery Dilatation on Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to evaluate the clinical impact of computed tomography (CT)–derived pulmonary artery dilatation (PAD) in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundSeveral studies have reported an association between pulmonary hypertension and cardiovascular events, but the prognostic value of PAD in patients undergoing TAVR remains unclear.MethodsThe preprocedural computed tomographic studies of patients who underwent TAVR at Cedars-Sinai Medical Center between November 2013 and December 2017 were analyzed. Patients were divided into 2 groups according to the presence of PAD assessed on CT (pulmonary artery [PA] diameter ≥29 mm). The primary endpoint was all-cause mortality at 2 years.ResultsA total of 895 patients were included (mean age 81.3 ± 8.5 years), with a mean Society of Thoracic Surgeons score of 4.8%. The median PA diameter was 28.0 mm, and PAD was observed in 369 patients (41.2%). Compared with the no-PAD group, the PAD group had higher Society of Thoracic Surgeons scores and higher rates of atrial fibrillation, chronic kidney disease, and chronic obstructive pulmonary disease. The PAD group had higher 2-year all-cause mortality than the no-PAD group (28.9% vs 12.8%; P < 0.001), and PAD was independently associated with mortality (adjusted HR: 2.21; 95% CI: 1.44-3.39; P < 0.001). Furthermore, PAD had strong prognostic power in the subgroup analysis, stratified according to PA pressure (>36 mm Hg).ConclusionsCT-derived PAD is a significant prognostic factor in patients undergoing TAVR.     

The Natural History of Nonculprit Lesions in STEMI: An FFR Substudy of the Compare-Acute Trial

ObjectivesThe aim of this study was to determine the prognostic value of fractional flow reserve (FFR) in non-infarct-related arteries (IRAs) in ST-segment elevation myocardial infarction (MI).BackgroundPatients with ST-segment elevation MI often present with multivessel disease. The treatment of non-IRAs is debated. The applicability of FFR has not been widely proved.MethodsOutcomes were analyzed in all patients in the Compare-Acute (Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD) trial in whom, after successful primary percutaneous coronary intervention, non-IRAs were interrogated using FFR and treated medically. The treating cardiologist was blinded to the FFR value. The primary endpoint was the composite of cardiovascular mortality, target vessel–related (non-IRA with FFR measurement at primary percutaneous coronary intervention) nonfatal MI, and target vessel revascularization: major adverse cardiac events (MACE) at 24 months.ResultsA total of 751 patients (963 vessels) were included. Target non-IRAs with MACE had lower FFR compared with those without (0.78 vs. 0.84, respectively; p < 0.001). The median FFR of non-IRAs with TVR was lower than that of those without (0.79 vs. 0.85, respectively; p < 0.001). The difference was significant in all vessels. The median FFR of target non-IRAs with MI was lower than that of those without (0.79 vs. 0.84, respectively; p = 0.016). The MACE rate was significantly (p < 0.001) higher in the lowest of FFR tertiles (<0.80) compared with the others (0.80 to 0.87 and ≥0.88).ConclusionsIn patients with ST-segment elevation MI with multivessel disease, FFR measured in the medically treated non-IRA immediately after successful primary percutaneous coronary intervention shows a nonlinear and inverse risk continuum of MACE. Importantly, worsening prognosis is demonstrated around the cutoff of 0.80.     

Dual Antiplatelet Therapy Discontinuation,Platelet Reactivity,and Adverse Outcomes After Successful Percutaneous Coronary Intervention

ObjectivesThe purpose of this study was to assess the extent to which the association between premature dual antiplatelet therapy (DAPT) discontinuation and excess risk of thrombotic events varies according to the reason and timing of DAPT discontinuation and whether high on-treatment platelet reactivity (HPR) influences the risk of thrombotic events after premature DAPT discontinuation.BackgroundDAPT after percutaneous coronary intervention (PCI) suppresses platelet reactivity, and HPR on clopidogrel after PCI is associated with an increased risk of thrombotic events.MethodsADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients successfully treated with coronary drug-eluting stents that assessed HPR on clopidogrel. For patients who discontinued aspirin or clopidogrel at any time during the study, the reasons for discontinuation were systematically categorized.ResultsPlanned DAPT discontinuation occurred within 2 years in 3,203 (37.3%) patients. One thousand four hundred eighteen (16.5%) patients discontinued DAPT for unplanned reasons, including surgery or trauma (n = 768 [8.9%]), patient nonadherence (n = 321 [3.7%]), bleeding complications (n = 264 [3.1%]), and drug allergy or hypersensitivity (n = 113 [1.3%]). Unplanned but not planned DAPT discontinuation was associated with an increased risk of a major adverse cardiac event (MACE, defined as the composite of cardiac death, myocardial infarction, or stent thrombosis); with highest risk within 3 months after PCI (adjusted HR: 7.65, 95% CI: 2.77-21.10 vs adjusted HR: 2.47, 95% CI: 1.70-3.58 for unplanned DAPT discontinuation ≥3 months after PCI). MACE risk after DAPT discontinuation was not moderated by HPR (P_interaction = 0.91).ConclusionsIn this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)     

Impact of Mediterranean diet on metabolic and inflammatory status of patients with polyvascular atherosclerotic disease

Background and aimsThe Mediterranean Diet (MD) represents a key player in cardiovascular disease prevention. Therefore, we aimed to assess the relationship between adherence to the MD and inflammatory, lipid and glycemic profile in patients affected by polyvascular atherosclerotic disease (PAD). We also investigated the incidence of long-term major adverse cardiovascular events (MACEs) according to MD adherence.Methods and resultsWe enrolled 107 patients with PAD, defined as the simultaneous involvement of at least two vascular districts. Adherence to the MD was estimated through a 9-item simplified form of the Mediterranean Diet Score. Improved fasting glycemic and LDL-cholesterol levels were reported in the high-adherence group compared with the low-adherence group (p < 0.001 and p = 0.0049, respectively). Both C-reactive protein and platelet-to-lymphocyte ratio were significantly lower in high-adherence patients than those with poor adherence to the MD (p = 0.0045 and p = 0.008, respectively). During follow-up (mean 34 ± 11 months), fatal events happened exclusively in the low-adherence group (58%), with an event-free survival of 37% compared with 87% in the moderate-adherence group and 70% in the high-adherence group (log-rank p-value < 0.001). Low adherence to the MD was associated with a higher incidence of MACEs in the Cox regression model adjusted for atherosclerotic risk factors (HR 12.23, 95% CI 4.00–37.39).ConclusionsHigh adherence to Mediterranean dietary pattern seems to be associated with improving inflammatory and metabolic status in patients suffering from PAD, potentially translating into better long-term cardiovascular outcomes. These findings provide evidence regarding the relevance of MD as a secondary preventive tool in this high-risk population.     

Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario,Canada

BackgroundRandomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG.ObjectivesThe purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease.MethodsClinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model.ResultsAfter exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG.ConclusionsCABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG.     

Impact of Periprocedural Adverse Events After PCI and CABG on 5-Year Mortality: The EXCEL Trial

BackgroundThe relative risks for different periprocedural major adverse events (MAE) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on subsequent mortality have not been described.ObjectivesThe aim of this study was to assess the association between periprocedural MAE occurring within 30 days postprocedure and early and late mortality after left main coronary artery revascularization by PCI and CABG.MethodsIn the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, patients with left main disease were randomized to PCI vs CABG. The associations between 12 prespecified nonfatal MAE and subsequent 5-year all-cause and cardiovascular death in 1,858 patients were examined using logistic regression.ResultsOne or more nonfatal MAE occurred in 111 of 935 patients (11.9%) after PCI and 419 of 923 patients (45.4%) after CABG (P < 0.0001). Patients with MAE were older and had more baseline comorbidities. Within 5 years, all-cause death occurred in 117 and 87 patients after PCI and CABG, respectively. Experiencing an MAE was a strong independent predictor of 5-year mortality after both PCI (adjusted OR: 4.61; 95% CI: 2.71-7.82) and CABG (adjusted OR: 3.25; 95% CI: 1.95-5.41). These associations were present within the first 30 days and between 30 days and 5 years postprocedure. Major or minor bleeding with blood transfusion ≥2 U was an independent predictor of 5-year mortality after both procedures. Stroke, unplanned revascularization for ischemia, and renal failure were significantly associated with mortality only after CABG.ConclusionsIn the EXCEL trial, nonfatal periprocedural MAE were strongly associated with early and late mortality after both PCI and CABG for left main disease.