Safety and Efficacy of Ticagrelor Monotherapy in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Individual Patient Data Meta-Analysis of TWILIGHT and TICO Randomized Trials.

BACKGROUND: Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. METHODS: We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. RESULTS: The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24-0.56]; P<0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68-1.21]; P=0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. CONCLUSIONS: Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Prognostic impact of in-stent restenosis in normal weight, overweight, and obese patients undergoing percutaneous coronary intervention.

BACKGROUND: Among patients undergoing percutaneous coronary intervention (PCI), in-stent restenosis (ISR) is related with a worse prognosis, while higher body mass index (BMI) values are associated with better outcomes. It is unclear whether the prognostic impact of ISR varies in function of BMI. METHODS: Patients undergoing PCI at a large center from 2012 to 2019 not presenting with an acute myocardial infarction (MI) were included. Subjects with BMI < 18.5 kg/m2 or treated with bare metal stents were excluded. Patients were stratified according to type of lesion treated (ISR vs. no-ISR) and into four BMI categories: normal weight (BMI 18.5-25 kg/m2 ), overweight (25.0-29.9 kg/m2 ), class I obesity (30.0-34.9 kg/m2 ), class II-III obesity (≥35.0 kg/m2 ). The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, MI, and target vessel revascularization (TVR) at 1 year. RESULTS: Out of 16,234 patients, 3694 (23%) underwent PCI for ISR. ISR as compared to no-ISR was associated with a consistent increased risk of MACE within the normal weight (18.8% vs. 7.8%, adj. hazard ratio (HR): 1.99, 95% confidence interval [CI]: 1.51-2.64), overweight (19.1% vs. 6.4%, adj. HR: 2.35, 95% CI: 1.91-2.88), class I obesity (18.3% vs. 6.8%, adj. HR: 1.95, 95% CI: 1.47-2.57), and class II-III obesity (16.4% vs. 7.4%, adj. HR: 1.61, 95% CI: 1.09-2.37) groups (interaction p-value: 0.192). The ISR-related risks were mostly driven by an excess of TVR. CONCLUSIONS: At 1 year, ISR was associated with an increased risk of MACE irrespective of BMI, mostly due to an excess of TVR after ISR.

Prevalence and prognostic impact of complex percutaneous coronary intervention among octogenarians.

BACKGROUND: The number of octogenarians referred to percutaneous coronary interventions (PCI) is rising steadily. The prevalence and prognostic impact of complex PCI (CPCI) in this vulnerable population has not been fully evaluated. METHODS: Patients ≥80 years old who underwent PCI between 2012 and 2019 at Mount Sinai Hospital were included. Patients were categorized based on PCI complexity, defined as the presence of at least one of the following criteria: use of atherectomy, total stent length ≥60 mm, ≥3 stents implanted, bifurcation treated with at least 2 stents, PCI involving ≥3 vessels, ≥3 lesions, left main, saphenous vein graft or chronic total occlusion. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), or target-vessel revascularization (TVR), within 1 year after PCI. Secondary outcomes included major bleeding. RESULTS: Among 2657 octogenarians, 1387 (52%) underwent CPCI and were more likely to be men and to have cardiovascular risk factors or comorbidities. CPCI as compared with no-CPCI was associated with a higher 1-year risk of MACE (16.6% vs. 11.1%, adjusted HR 1.3, 95% CI 1.06-1.77, p value 0.017), due to an excess of MI and TVR, and major bleeding (10% vs. 5.8%, adjusted HR 1.64, 95% CI 1.20-2.55, p value 0.002). CONCLUSIONS: Among octogenarians, CPCI was associated with a significantly higher 1-year risk of MACE, due to higher rates of MI and TVR but not of all-cause death, and of major bleeding. Strategies to reduce complications should be implemented in octogenarians undergoing CPCI.

Prognostic impact of peripheral artery disease in patients with and without high bleeding risk undergoing percutaneous coronary intervention.

BACKGROUND: Peripheral artery disease (PAD) is associated with worse outcomes after percutaneous coronary intervention (PCI). The aim of this study was to assess the prognostic impact of PAD according to high bleeding risk (HBR) status. METHODS: Consecutive patients undergoing PCI with drug-eluting stent implantation at a tertiary-care center (Mount Sinai Hospital) between 2012 and 2019 were stratified according to HBR and PAD status. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and stroke 1 year after PCI. Secondary outcomes included major bleeding. RESULTS: Out of 16,750 patients, 43% were HBR and 57% were no-HBR. Within the two groups, PAD patients were 14% and 6%, respectively, and were more likely to have comorbidities and to undergo complex PCI than no-PAD patients. Within the HBR group, PAD was associated with an increased risk of MACE (11.4% vs. 7.3%, hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.27-1.99, p < 0.001) and a numerical nonsignificant increase of major bleeding (8.5% vs. 6.9%, HR: 1.25, 95% CI: 0.98-1.59, p = 0.066) as compared with no-PAD. Among no-HBR patients, rates of MACE and major bleeding were numerically but not significantly higher in the PAD group. After multivariable adjustment, PAD was no longer a predictor of adverse outcomes, irrespective of HBR status. CONCLUSIONS: At 1-year after PCI, PAD was associated with increased 1-year risks of MACE in HBR patients. After adjustment for cardiovascular risk factors and comorbidities, the effect of PAD on adverse events was largely attenuated.

Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: Insights from a large PCI registry.

BACKGROUND: The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3-month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population. METHODS: Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. Patients were stratified into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI. RESULTS: Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients. CONCLUSION: Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and MI and a moderately elevated risk of bleeding.

Impact of complex percutaneous coronary intervention features on clinical outcomes in patients with or without chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at higher risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). Complex PCI (CPCI) is associated with higher rates of ischemic complications. Whether CPCI confers an additive risk of adverse events in CKD patients is unclear. METHODS: Patients who underwent PCI at a single tertiary-care-center between 2012 and 2019 were stratified by CKD status and CPCI. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1-year follow-up. Secondary outcomes included the individual components of the primary outcome and major bleeding. RESULTS: Out of 15,071 patients, 4537 (30.1%) had CKD and 10,534 (69.9%) had no CKD. Patients undergoing CPCI were 1151 (25.4%) and 2983 (28.3%) in the two cohorts, respectively. At one year, CPCI compared with no CPCI was associated with higher risk of MACE in both CKD (Adj. HR 1.72, 95% confidence interval [CI] 1.45-2.06, p < 0.001) and no-CKD patients (Adj. hazard ratios [HR] 2.19, 95% CI 1.91-2.51, p < 0.001; p of interaction 0.057), determined by an excess of death, MI and TVR in CKD patients and of TVR and MI only in no-CKD. CPCI was related with a consistent increase of major bleeding in the CKD (Adj. HR 1.49, 95% CI 1.18-1.87, p < 0.001) and no-CKD group (Adj. HR 1.23, 95% CI 0.98-1.54, p = 0.071, p of interaction 0.206). CONCLUSION: At 1-year follow-up, CPCI was associated with higher risk of MACE and major bleeding irrespective of concomitant CKD. CPCI predicted mortality in CKD patients only.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials.

AIMS: The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. METHODS AND RESULTS: We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin-kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74-0.86; I  2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67-0.89; I  2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78-0.89; I  2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). CONCLUSION: Proprotein convertase subtilisin-kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.

A contemporary simple risk score for prediction of contrast-associated acute kidney injury after percutaneous coronary intervention: derivation and validation from an observational registry.

BACKGROUND: Contrast-associated acute kidney injury can occur after percutaneous coronary intervention (PCI). Prediction of the contrast-associated acute kidney injury risk is important for a tailored prevention and mitigation strategy. We sought to develop a simple risk score to estimate contrast-associated acute kidney injury risk based on a large contemporary PCI cohort. METHODS: Consecutive patients undergoing PCI at a large tertiary care centre between Jan 1, 2012, and Dec 31, 2020, with available creatinine measurements both before and within 48 h after the procedure, were included; only patients on chronic dialysis were excluded. Patients treated between 2012 and 2017 comprised the derivation cohort and those treated between 2018 and 2020 formed the validation cohort. The primary endpoint was contrast-associated acute kidney injury, defined according to the Acute Kidney Injury Network. Independent predictors of contrast-associated acute kidney injury were derived from multivariate logistic regression analysis. Model 1 included only pre-procedural variables, whereas Model 2 also included procedural variables. A weighted integer score based on the effect estimate of each independent variable was used to calculate the final risk score for each patient. The impact of contrast-associated acute kidney injury on 1-year deaths was also evaluated. FINDINGS: 32 378 PCI procedures were performed and screened for inclusion in the present analysis. After the exclusion of patients without paired creatinine measurements, patients on chronic dialysis, and multiple procedures, 14 616 patients were included in the derivation cohort (mean age 66·2 years, 29·2% female) and 5606 were included in the validation cohort (mean age 67·0 years, 26·4% female). Contrast-associated acute kidney injury occurred in 860 (4·3%) patients. Independent predictors of contrast-associated acute kidney injury included in Model 1 were: clinical presentation, estimated glomerular filtration rate, left ventricular ejection fraction, diabetes, haemoglobin, basal glucose, congestive heart failure, and age. Additional independent predictors in Model 2 were: contrast volume, peri-procedural bleeding, no flow or slow flow post procedure, and complex PCI anatomy. The occurrence of contrast-associated acute kidney injury in the derivation cohort increased gradually from the lowest to the highest of the four risk score groups in both models (2·3% to 34·9% in Model 1, and 2·0% to 38·8% in Model 2). Inclusion of procedural variables in the model only slightly improved the discrimination of the risk score (C-statistic in the derivation cohort: 0·72 for Model 1 and 0·74 for model 2; in the validation cohort: 0·84 for Model 1 and 0·86 for Model 2). The risk of 1-year deaths significantly increased in patients with contrast-associated acute kidney injury (10·2% vs 2·5%; adjusted hazard ratio 1·76, 95% CI 1·31-2·36; p=0·0002), which was mainly due to excess 30-day deaths. INTERPRETATION: A contemporary simple risk score based on readily available variables from patients undergoing PCI can accurately discriminate the risk of contrast-associated acute kidney injury, the occurrence of which is strongly associated with subsequent death. FUNDING: None.

Ticagrelor with or without Aspirin in High-Risk Patients after PCI.

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Diabetes mellitus in transfemoral transcatheter aortic valve implantation: a propensity matched analysis.

BACKGROUND: Diabetes Mellitus (DM) affects a third of patients with symptomatic severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). DM is a well-known risk factor for cardiac surgery, but its prognostic impact in TAVI patients remains controversial. This study aimed to evaluate outcomes in diabetic patients undergoing TAVI. METHODS: This multicentre registry includes data of > 12,000 patients undergoing transfemoral TAVI. We assessed baseline patient characteristics and clinical outcomes in patients with DM and without DM. Clinical outcomes were defined by the second valve academic research consortium. Propensity score matching was applied to minimize potential confounding. RESULTS: Of the 11,440 patients included, 31% (n = 3550) had DM and 69% (n = 7890) did not have DM. Diabetic patients were younger but had an overall worse cardiovascular risk profile than non-diabetic patients. All-cause mortality rates were comparable at 30 days (4.5% vs. 4.9%, RR 0.9, 95%CI 0.8-1.1, p = 0.43) and at one year (17.5% vs. 17.4%, RR 1.0, 95%CI 0.9-1.1, p = 0.86) in the unmatched population. Propensity score matching obtained 3281 patient-pairs. Also in the matched population, mortality rates were comparable at 30 days (4.7% vs. 4.3%, RR 1.1, 95%CI 0.9-1.4, p = 0.38) and one year (17.3% vs. 16.2%, RR 1.1, 95%CI 0.9-1.2, p = 0.37). Other clinical outcomes including stroke, major bleeding, myocardial infarction and permanent pacemaker implantation, were comparable between patients with DM and without DM. Insulin treated diabetics (n = 314) showed a trend to higher mortality compared with non-insulin treated diabetics (n = 701, Hazard Ratio 1.5, 95%CI 0.9-2.3, p = 0.08). EuroSCORE II was the most accurate risk score and underestimated 30-day mortality with an observed-expected ratio of 1.15 in DM patients, STS-PROM overestimated actual mortality with a ratio of 0.77 and Logistic EuroSCORE with 0.35. CONCLUSION: DM was not associated with mortality during the first year after TAVI. DM patients undergoing TAVI had low rates of mortality and other adverse clinical outcomes, comparable to non-DM TAVI patients. Our results underscore the safety of TAVI treatment in DM patients. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT03588247).

Two-year clinical outcomes after successful transcatheter aortic valve implantation with balloon-expandable versus self-expanding valves: A subanalysis of the GALILEO trial.

BACKGROUND: Midterm data comparing clinical outcomes after successful implantation of self-expanding and balloon-expandable transcatheter heart valves (THV) are limited. We aimed to compare 2-year outcomes after successful transcatheter aortic valve implantation (TAVI) with the Edwards balloon-expandable or the Medtronic self-expanding THV. METHODS: Two-year outcomes were analyzed according to the implanted THV in the GALILEO trial. Major adverse cardiac and cerebrovascular events (MACCE) was a composite of all-cause death or thromboembolic events including stroke, myocardial infarction, symptomatic valve thrombosis, systemic embolism, deep-vein thrombosis, or pulmonary embolism. RESULTS: Among 1644 patients recruited in 136 centers across 16 countries between 2015 and 2018, 499 received a self-expanding and 757 patients received a balloon-expandable THV. Patients treated with a self-expanding THV were more likely to be female, and had higher surgical risk, lower hemoglobin levels, and more frequent valve-in-valve procedures than those with a balloon-expandable THV. After multivariable adjustment, there were no significant differences in major clinical outcomes between self-expanding versus balloon-expandable THV: MACCE (17.0% vs. 13.4%, adjusted-hazard ratios [HR] 1.18, 95% confidence intervals [CI]: 0.82-1.69); all-cause death (11.4% vs. 9.3%, adjusted-HR 1.26; 95% CI: 0.78-2.05); cardiovascular death (8.5% vs. 4.0%, adjusted-HR 1.53; 95% CI: 0.82-2.86), any stroke (5.1% vs. 3.7%, adjusted-HR 0.86; 95% CI: 0.43-1.73); major or life-threatening bleeding (5.9% vs. 6.8%, adjusted-HR 0.93; 95% CI: 0.53-1.63). CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. NCT02556203. CONCLUSIONS: Two-year follow-up data from the GALILEO trial indicate that successful TAVI either with self-expanding or balloon-expandable THVs according to physician discretion did not show difference in rates of MACCE.

Performance of the academic research consortium high-bleeding risk criteria in patients undergoing PCI for acute myocardial infarction.

Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are at increased risk for thrombotic and bleeding complications compared to patients with chronic coronary syndrome (CCS). The academic research consortium (ARC) recently suggested a set of criteria to identify patients at high bleeding risk (HBR). We sought to evaluate the performance of the ARC-HBR criteria among patients undergoing PCI according to clinical presentation. We included all consecutive patients undergoing PCI at a tertiary-care center. Patients were deemed at HBR if they fulfilled ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary bleeding endpoint was a composite of in-hospital or post-discharge bleeding at 1-year follow-up. Secondary outcomes included all-cause death and myocardial infarction. Out of 6068 patients, 1391 (22.9 %) presented with AMI and were more often at HBR than those with CCS (46.9 % vs. 43.0 %, p = 0.01). HBR patients had a higher risk for the primary bleeding endpoint than non-HBR, irrespective of the clinical indication for PCI (AMI: 19.5 % vs. 5.5 %; HR 3.86, 95 % CI 2.63-5.69; CCS: 6.8 % vs. 2.6 %; HR 2.65, 95 % CI 1.92-3.68; p-interaction = 0.11). Secondary outcomes followed a similar trend. After multivariable adjustment, AMI presentation remained significantly associated with increased risk for bleeding at 1 year (HR 1.64, 95 % CI 1.13-2.38, p = 0.01). The ARC-HBR criterion associated with the highest bleeding risk was severe/end-stage chronic kidney disease in AMI and moderate/severe anemia in CCS. The ARC-HBR framework successfully identified AMI and CCS patients with increased risk for bleeding complications at 1 year post-PCI. Figure prepared with BioRender.

Perioperative risk and antiplatelet management in patients undergoing non-cardiac surgery within 1 year of PCI.

Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as ≥ 2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.

Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR.

AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD.

AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.

Safety and efficacy of the bioabsorbable polymer everolimus-eluting stent versus durable polymer drug-eluting stents in high-risk patients undergoing PCI: TWILIGHT-SYNERGY.

BACKGROUND: Data examining the safety and efficacy of the bioabsorbable polymer (BP) drug-eluting stent (DES) as compared with durable polymer (DP) DES in high-risk patients undergoing percutaneous coronary intervention (PCI) remain limited. METHODS: We conducted a pre-specified analysis among patients enrolled in the TWILIGHT trial treated with the SYNERGY BP-DES or a DP-DES. Following successful PCI and 3 months of ticagrelor plus aspirin, patients were randomized to aspirin or placebo for 1 year; DES choice was at physician discretion. The primary endpoint was target lesion failure (TLF) [composite of cardiac death, target vessel myocardial infarction (MI), clinically driven target lesion revascularization (TLR) or definite/probable stent thrombosis (ST)]. RESULTS: Among enrolled participants (N = 9,006), 653 were treated exclusively with the SYNERGY BP-DES and 6,404 with a comparator DP-DES. Over 15 months, TLF rates were 6.4 and 6.1% among those receiving a SYNERGY BP-DES and a DP-DES, respectively (adjusted HR 0.93; 95% CI 0.64-1.35; p = .72). The effect of ticagrelor monotherapy on Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding and the composite of all-cause death, MI or stroke was uniform across DES groups (both pint > .10). CONCLUSIONS: The safety and efficacy profile of the SYNERGY BP-DES is comparable to that of contemporary DP-DES in high-risk patients undergoing PCI. Compared to ticagrelor plus aspirin, the effect of ticagrelor monotherapy is consistent among patients receiving SYNERGY BP-DES or DP-DES.

Radial versus femoral access for coronary interventions: An updated systematic review and meta-analysis of randomized trials.

OBJECTIVE: It is still debated if benefits associated with radial versus femoral access for coronary angiography and percutaneous coronary interventions (PCI) are due to the access site selection itself, operator expertise or other underlying mechanisms. METHODS: We searched PubMed, Embase, and meeting abstracts for randomized trials comparing radial versus femoral access site for coronary angiography and PCI. Primary safety endpoint was major bleeding. Coprimary efficacy endpoints were stroke and myocardial infarction (MI). This study is registered with PROSPERO. RESULTS: We identified 31 trials (30,096 patients, PCI performed in 21,225 patients). Radial compared to femoral access was associated with a significant risk reduction in major bleeding (OR 0.53, 95%CI 0.42-0.66, I2  = 3.3%). Findings were consistent regardless of clinical characteristics or whether coronary angiography was performed with or without PCI. The benefit of radial access was significantly increased in studies published before 2010 and in patients with chronic coronary syndrome. Risk for stroke (OR 1.11, 95%CI 0.76-1.64, I2  = 0%) and MI (OR 0.90, 95%CI 0.79-1.04, I2  = 0%) were comparable between the groups. Risk for mortality and vascular complications were significantly lower with radial than femoral access. CONCLUSION: In patients undergoing coronary angiography and PCI, radial access is associated with a significant risk reduction in bleeding, vascular complications, and mortality compared to femoral access. The risk of stroke or MI were comparable in patients with radial or femoral access.

Impact of anemia on short-term outcomes after TAVR: A subgroup analysis from the BRAVO-3 randomized trial.

OBJECTIVES: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown. METHODS: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days. RESULTS: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (pinteraction  = 0.71 for NACE, pinteraction  = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days. CONCLUSIONS: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.