Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification.

AIMS The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. CONCLUSIONS In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. CLINICALTRIALS.GOV IDENTIFIER NCT02241291

The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study

Aims The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. Methods and results In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (−0.25 mm, 95% CI −0.36 to −0.17 mm) when compared with patients without NA (−0.13 mm, 95% CI −0.17 to −0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. Conclusions In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms. SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT0061708

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

Aims Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with ‘paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. Methods and results Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm2 m−2, stroke volume index ≤35 mL/m2, ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm2 m−2, EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG: 2006 ± 586 vs. LEF-LG: 2216 ± 765 dyne s m−5, P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG: 6.9 ± 1.9 vs. LEF-LG: 7.7 ± 2.5 mmHg mL−1 m−2, P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG: 71.7% vs. LEF-LG: 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). Conclusion TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar exten

Impact of atrial fibrillation on clinical outcomes among patients with coronary artery disease undergoing revascularisation with drug-eluting stents

Coronary artery disease (CAD) and atrial fibrillation (AF) are major determinants of morbidity and mortality. A combined treatment with antiplatelet agents and vitamin K antagonists limits the risk of stent thrombosis and stroke while increasing the rate of bleeding. The objective of this study was to investigate the impact of atrial fibrillation (AF) on long-term clinical outcomes in patients with CAD undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES)

Differences in coronary plaque characteristics between patients with and those without peripheral arterial disease.

INTRODUCTION Cardiovascular mortality of patients with combined peripheral arterial disease (PAD) and coronary artery disease (CAD) is twice as high as that in those with either disease alone. It is known that patients with PAD undergoing percutaneous coronary intervention have a higher incidence of adverse cardiac events such as myocardial infarction or target vessel revascularization. OBJECTIVE In this study, we compared the detailed characteristics of culprit and nonculprit plaques between patients with and those without PAD using optical coherence tomography. PATIENTS AND METHODS We performed propensity score matching using the following variables: (i) age; (ii) sex; (iii) clinical presentation; (iv) diabetes mellitus; (v) hyperlipidemia; (vi) smoking; (vii) hypertension; (viii) BMI; and (ix) coronary lesion location. Finally, we matched 34 culprit lesions and 30 nonculprit lesions in patients with PAD to 68 culprit lesions and 60 nonculprit lesions in patients without PAD (1 : 2 ratio). RESULTS In culprit lesions, PAD patients when compared with those without PAD had a higher prevalence of lipid-rich plaque (73.5 vs. 51.5%; P=0.033), higher lipid index (1744±1110 vs. 1246±656; P=0.043), calcification (79.4 vs. 58.8%; P=0.039), macrophage accumulation (70.6 vs. 48.5%; P=0.034), and cholesterol crystals (32.4 vs. 10.3%; P=0.006). In nonculprit lesions, PAD patients had a higher prevalence of calcification (76.7 vs. 55.0%; P=0.046), macrophage accumulation (63.3 vs. 38.3%; P=0.025), and cholesterol crystals (36.7 vs. 16.7%; P=0.034). CONCLUSION Our study suggests greater coronary plaque vulnerability in both culprit and nonculprit lesions in patients with PAD. This observation underscores the need for more aggressive risk management in patients with combined PAD and coronary artery disease

TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction

Background: Current STEMI guideline recommendations limit the use of prasugrel to clopidogrel-naïve patients. However, in daily clinical practice a considerable proportion of STEMI patients undergoing primary PCI are preloaded with clopidogrel. Whether the use of prasugrel in clopidogrel pretreated STEMI patients is safe remains unknown. Similarly, the efficacy of a combined loading dose regimen has not been evaluated. Methods: Between 1 September 2009 and 15 October 2012, a total of 1,157 STEMI patients were included in the randomized COMFORTABLE AMI trial (NCT 00962416) and 891 STEMI patients in the SPUM ACS registry (NCT 01000701) at 12 centers. Patients were divided into three groups according to type of peri-procedural antiplatelet loading: (1) Clopidogrel and subsequent Prasugrel loading dose [CP], (2) Prasugrel loading dose alone [P] (3) Clopidogrel loading dose alone [C]; 23 patients were excluded because they were not exposed to Clopidogrel and Prasugrel. The primary safety endpoint was the rate of BARC type 3, 4 and 5 bleeding at 30 days. The primary efficacy endpoint was the composite of cardiac death, nonfatal MI and nonfatal stroke at 30 days. Outcomes were analyzed using Cox's Regressions (crude) and multinomial ITPW weighted Cox's Regressions. Results: A total of 2,025 patients were analysed of whom 428 (21.1%) had received CP, 447 (22.1%) patients P alone, and 1,150 (56.8%) patients C alone. The primary safety endpoint was observed among 1.2% of CP, 1.6% of P, and 1.5% of C patients (CP vs C ad. HR 0.99 (0.36-2.72), PC vs P ad. HR 0.73 (0.22-2.41). The primary safety endpoint occurred less frequently among CP (1.9%) compared with C patients (5.0%, adjusted HR 0.47 (0.22-1.00), but with similar frequency among P and C patients (2.9% vs 5.0%, ad. HR 0.68 (0.27-1.73). The net clinical benefit outcome parameter tended to be lower among CP (2.8%) compared with C patients (6.3%, ad. HR 0.56 (0.30-1.05), whereas no significant difference was observed between P and C patients (3.8% vs 6.3%, ad. HR 0.85 (0.39-1.86). Conclusions: Among STEMI patients preloaded with Clopidogrel, the concurrent administration of a Prasugrel loading dose appears safe and potentially more effective than Clopiogrel alone

Effect of Timing of Staged Percutaneous Coronary Intervention on Clinical Outcomes in Patients With Acute Coronary Syndromes.

Background Complete revascularization reduces cardiovascular events in patients with acute coronary syndromes (ACSs) and multivessel disease. The optimal time point of non-target-vessel percutaneous coronary intervention (PCI) remains a matter of debate. The aim of this study was to investigate the impact of early (<4 weeks) versus late (≥4 weeks) staged PCI of non-target-vessels in patients with ACS scheduled for staged PCI after hospital discharge. Methods and Results All patients with ACS undergoing planned staged PCI from 2009 to 2017 at Bern University Hospital, Switzerland, were analyzed. Patients with cardiogenic shock, in-hospital staged PCI, staged cardiac surgery, and multiple staged PCIs were excluded. The primary end point was all-cause death, recurrent myocardial infarction and urgent premature non-target-vessel PCI. Of 8657 patients with ACS, staged revascularization was planned in 1764 patients, of whom 1432 patients fulfilled the eligibility criteria. At 1 year, there were no significant differences in the crude or adjusted rates of the primary end point (7.8% early versus 10.8% late, hazard ratio [HR], 0.72 [95% CI, 0.47-1.10], P=0.129; adjusted HR, 0.80 [95% CI, 0.50-1.28], P=0.346) and its individual components (all-cause death: 1.5% versus 2.9%, HR, 0.52 [95% CI, 0.20-1.33], P=0.170; adjusted HR, 0.62 [95% CI, 0.23-1.67], P=0.343; recurrent myocardial infarction: 4.2% versus 4.4%, HR, 0.97 [95% CI, 0.475-1.10], P=0.924; adjusted HR, 1.03 [95% CI, 0.53-2.01], P=0.935; non-target-vessel PCI, 3.9% versus 5.7%, HR, 0.97 [95% CI, 0.53-1.80], P=0.928; adjusted HR, 1.19 [95% CI, 0.61-2.34], P=0.609). Conclusions In this single-center cohort study of patients with ACS scheduled to undergo staged PCI after hospital discharge, early (<4 weeks) versus late (≥4 weeks) staged PCI was associated with a similar rate of major adverse cardiac events at 1 year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291

Progression of cardiac allograft vasculopathy assessed by serial three-vessel quantitative coronary angiography.

BACKGROUND:The purpose of the present study was to assess the short- and long-term progression of cardiac allograft vasculopathy (CAV) using serial 3-vessel quantitative coronary angiography (QCA). METHODS:CAV progression was assessed using serial 3-vessel QCA analysis at baseline, 1-year and long-term angiographic follow-up (8.5±3.7 years) after heart transplantation. The change in minimal lumen diameter (MLD) and percent diameter stenosis (%DS) was serially assessed within matched segments. Patients were graded according to the ISHLT-CAV classification and grouped as ISHLT-CAV0 and ISHLT-CAV1-3. The primary endpoint was mean change in MLD and %DS. RESULTS:A total of 41 patients and 520 matched segments were available for serial 3-vessel QCA. Overall, MLD decreased non-significantly from baseline to 1-year follow-up and significantly from 1-year to the long-term angiographic follow-up (Δ-0.08mm/year [95%CI -0.11 to -0.05], P<0.001). %DS increased significantly from baseline to 1-year (Δ+0.96%/year [95%CI 0.04 to 1.88], P = 0.041) and from 1-year to long-term angiographic follow-up (Δ+0.61%/year [95%CI 0.33 to 0.88], P<0.001). ISHLT-CAV1-3 at 1 year and at long-term angiographic follow-up was observed in 22% and 61%, respectively. Between baseline and long-term angiographic follow-up, a significant reduction in MLD was observed within both groups without a significant difference in the reduction between the two groups (ISHLT-CAV0: median -0.49mm [IQR -0.54 to -0.43] vs. ISHLT-CAV1-3: median -0.40mm [IQR -0.44 to -0.35], P = 0.4). CONCLUSION:The current data suggest that QCA can't predict CAV beyond 1 year, but, QCA affirmed that CAV progresses to a similar extent in patients who do not develop visual CAV during long-term follow-up

Ten-year clinical outcomes of first-generation drug-eluting stents: the Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) VERY LATE trial.

AIMS Compared with bare metal stents, first-generation drug-eluting stents (DES) are associated with an increased risk of late restenosis and stent thrombosis (ST). Whether this risk continues or attenuates during long-term follow-up remains unknown. METHODS AND RESULTS We extended the follow-up of 1012 patients [sirolimus-eluting stent (SES): N = 503 and paclitaxel-eluting stent (PES): N = 509] included in the all-comers, randomized Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) trial to 10 years. Follow-up was complete in 895 patients (88.4%) at 10 years. At 1, 5, and 10 years of follow-up, rates of ischaemia-driven target lesion revascularization (ID-TLR) were 8.1%, 14.6% and 17.7%, respectively, and rates of ST were 1.9%, 4.5% and 5.6%, respectively. The annual risks of ID-TLR and definite ST were significantly higher between 1 and 5 years as compared with the 5- to 10-year period [ID-TLR: 1.8% vs. 0.7%/year, hazard ratio (HR) 0.36, 95% confidence intervals (95% CI) 0.21-0.62, P < 0.001; definite ST: 0.67% vs. 0.23%/year, HR 0.31, 95% CI 0.13-0.75, P = 0.01]. The attenuation of the risk of ID-TLR and ST beyond 5 years was independent of age. Major adverse events (cardiac death, myocardial infarction, and ID-TLR) occurred in 33.7% of SES- and 33.8% of PES-treated patients (P = 0.72). CONCLUSIONS During long-term follow-up through 10 years, the annual risks of ID-TLR and definite ST significantly decreased beyond 5 years after first-generation DES implantation. These findings may have important implications for secondary prevention after percutaneous coronary intervention with first-generation DES including long-term antiplatelet therapy. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00297661