Jaya Chandrasekhar

Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study

BACKGROUND Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. METHODS TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. CONCLUSIONS TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women Undergoing Complex Percutaneous Coronary Artery Revascularization from the WIN-DES Collaborative Patient-Level Pooled Analysis

OBJECTIVES The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex percutaneous coronary intervention (CPCI). BACKGROUND Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown. METHODS We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. RESULTS Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity. CONCLUSIONS Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.

Sex‐related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: Results from the PROMETHEUS Study

Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under‐treatment. We sought to compare the 1‐year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort.

Use of prasugrel vs clopidogrel and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention in contemporary clinical practice: Results from the PROMETHEUS study.

Background and objectives We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. Methods PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90 days, a composite of all‐cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. Results Of 19,914 patients (mean age 64.4 years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel‐treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90 days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50‐0.67, P < .0001) and bleeding (1.9% vs 2.9%, HR 0.65, 95% CI 0.51‐0.83, P < .001). After propensity stratification, associations were attenuated and no longer significant for either outcome. Results remained consistent using different approaches to adjusting for potential confounders. Conclusions In contemporary clinical practice, patients receiving prasugrel tend to have a lower‐risk profile compared with those receiving clopidogrel. The lower ischemic and bleeding events associated with prasugrel use were no longer evident after accounting for these baseline differences.

Patterns and associations between DAPT cessation and 2-year clinical outcomes in left main/proximal LAD versus other PCI: Results from the Patterns of Non-Adherence to Dual Antiplatelet Therapy in Stented Patients (PARIS) registry

OBJECTIVES Percutaneous coronary intervention (PCI) of the left main (LM) or proximal left anterior descending artery (pLAD) is considered high-risk as these segments subtend substantial left ventricular myocardial area. We assessed the patterns and associations between dual antiplatelet therapy (DAPT) cessation and 2-year outcomes in LM/pLAD vs. other PCI from the all-comer PARIS registry. METHODS Two-year major adverse cardiovascular events (MACE) were a composite of cardiac death, myocardial infarction, definite/probable stent thrombosis or target lesion revascularization. DAPT cessation was predefined as physician-guided permanent discontinuation, temporary interruption, or non-recommended disruption due to non-compliance or bleeding. RESULTS Of the study population (n=5018), 25.0% (n=1252) underwent LM/pLAD PCI and 75.0% (n=3766) PCI to other segments. Compared to others, LM/pLAD patients presented with fewer comorbidities, less frequent acute coronary syndromes but more multivessel and bifurcation disease treated with greater stent lengths. Two-year adjusted risk of MACE (11.4% vs. 11.6%; HR 1.10, 95% CI 0.90-1.34, p=0.36) was similar between LM/pLAD vs. other patients. DAPT discontinuation was significantly higher (43.3% vs. 39.4%, p=0.01) in LM/pLAD patients with borderline significance for lower disruption (10.0% vs. 14.7%, p=0.059) compared to other patients. DAPT discontinuation was not associated with higher risk of MACE in LM/pLAD (HR 0.65, 95% CI 0.34-1.25) or other PCI groups (HR 0.67, 95% CI 0.47-0.95). CONCLUSIONS LM/pLAD PCI was not an independent predictor of 2-year MACE. Compared to other PCI, patients undergoing LM/pLAD PCI had higher rates of physician recommended DAPT discontinuation, however, discontinuation did not result in greater adverse events.

The Ideal Anticoagulation Strategy in ST-Elevation Myocardial Infarction

Heparin has been the principal anticoagulant in the management of ST-elevation myocardial infarction (STEMI) but has several limitations. Although glycoprotein IIb/IIIa inhibitors have been major adjuncts in previous years, in the era of novel P2Y12 receptor inhibitors they may have a greater role in bailout. Low molecular weight heparins have been extensively studied in fibrinolysis trials but data in primary percutaneous coronary intervention (PCI) are scarce. The direct thrombin inhibitor bivalirudin overcomes several shortcomings of heparins and has demonstrated a significant reduction in bleeding outcomes and net adverse cardiac events at the cost of increased acute stent thrombosis. This review discusses the pharmacology and clinical trial evidence for different anticoagulant treatment options in STEMI with a proposed selection strategy in contemporary primary PCI.

Radial artery occlusion: Preventing Insult to Injury

Intra‐arterial nitroglycerin prior to transradial sheath removal may reduce the incidence of radial artery occlusion (RAO). Operators must observe careful attention to all aspects of transradial catheterization, particularly patent hemostasis; as well as independently monitor the institutional incidence of RAO to prompt improvements in practice. Future studies on the impact of pre‐puncture ultrasound, novel sheaths, hemostatic devices, and potent oral and intravenous antithrombotic therapy on 30‐day RAO diagnosed by ultrasound may allow further reduction of RAO in a real‐world practice.

Sex‐based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO‐3 randomized trial

Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO‐3) trial of transfemoral TAVR.

Mortality pattern and cause of death in a long-term follow-up of patients with STEMI treated with primary PCI

Objective We aimed to assess the pattern of mortality and cause of death in a cohort of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods Consecutive patients with STEMI treated with primary PCI during 2006–2013 were evaluated with a mean follow-up of 3.5 years (1–8.4 years). We used hospital and general practice records and mortality data from The Australian National Death Index. Results Among 1313 patients (22.5% female) with mean age of 62.3±13.1 years, 181 patients (13.7%) died during long-term follow-up. In the first 7 days, 45 patients (3.4%) died, 76% of these due to cardiogenic shock. Between 7 days and 1 year, another 50 patients died (3.9%), 58% from cardiovascular causes and 22% from cancer. Beyond 1 year, there were 86 deaths with an estimated mean mortality rate of 2.05% per year, 36% of deaths were cardiovascular and 52% non-cardiovascular, including 29% cancer-related deaths. On multivariate analysis, age ≥75 years, history of diabetes, prior PCI, cardiogenic shock, estimated glomerular filtration rate (eGFR) <60 and symptom-to-balloon time >360 min were independent predictors of long-term mortality. In 16 patients who died of sudden cardiac death postdischarge, only 4 (25%) had ejection fraction ≤35% and would have been eligible for an implantable cardioverter defibrillator. Conclusions In the era of routine primary PCI, we found a mortality rate of 7.3% at 1 year, and 2.05% per year thereafter. Cause of death was predominantly cardiovascular in the first year and mainly non-cardiovascular after 1 year. Age, diabetes, prior PCI, cardiogenic shock, eGFR <60 and delayed treatment were independent predictors of mortality.

First Direct Aortic Retrievable Transcatheter Aortic Valve Implantation in Humans

We describe 2 cases in which transcatheter aortic valve implantation was performed with a Portico prosthesis (St Jude Medical, St Paul, MN) through a direct aortic approach. In 1 of the cases, prosthesis retrieval was needed during the procedure and was essential to the successful outcome. This is the first report, to our knowledge, of direct aortic Portico prosthesis implantation, and it highlights the significance of the retrievable nature of this device.