Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation.

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.

Impact of Valve Size on Prosthesis-Patient Mismatch and Aortic Valve Gradient After Transcatheter versus Surgical Aortic Valve Replacement.

OBJECTIVE: Limited data is available about the effect of implanted valve size on prosthesis-patient mismatch (PPM) incidence and aortic gradient (AG) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). We compared PPM incidence and postprocedural AG between TAVR and SAVR patients considering the impact of implanted valve size. METHODS: From March 20, 2012, to September 30, 2015, 563 consecutive patients underwent TAVR (n = 419) or isolated SAVR (n = 144). Postprocedural transthoracic echocardiography was obtained within 30 days; AG, effective orifice area (EOA), and EOA index were calculated. RESULTS: A total of 381 patients in TAVR group and 82 patients in SAVR group were included. Mean preoperative AG and mean aortic valve area were not significantly different between the 2 groups. Postprocedural AG was significantly lower in TAVR than SAVR group, 7.74 ± 5.39 versus 14.27 ± 8.16 (P < 0.001). Between patients who had TAVR and SAVR with a valve size ≤23 mm, SAVR patients were 3 times more likely to have greater than mild AG after the procedure, OR: 3.1 (95% CI, 1.1 to 8.9) (P < 0.001). PPM incidence was significantly higher in SAVR group than TAVR group, 44 (53.7%) versus 112 (29.4%), OR = 2.8 (95% CI, 1.7 to 4.5) (P < 0.001). The PPM incidence was also higher in SAVR group than TAVR group among those who had the procedures with a valve size ≤23 mm, 35 (64.8%) versus 56 (47.9%), OR = 2 (95% CI, 1.1 to 3.9) (P = 0.048). Postprocedural outcomes were comparable between the 2 groups. CONCLUSIONS: In comparison to SAVR, TAVR is associated with less PPM and lower AG, especially in patients receiving a valve size ≤23 mm.

Drug-Eluting Balloons Versus Everolimus-Eluting Stents for In-Stent Restenosis: A Meta-Analysis of Randomized Trials.

OBJECTIVES: Individual randomized trials comparing drug-eluting balloons (DEB) versus everolimus-eluting stents (EES) for in-stent restenosis (ISR) were underpowered for clinical end-points. The objective of this study was to compare the clinical outcomes of DEB versus EES for any ISR. MATERIALS & METHODS: Electronic databases were searched for randomized trials which compared DEB versus EES for any ISR (i.e., drug eluting or bare metal stents). Summary estimate risk ratios (RRs) were constructed using a DerSimonian and Laird random effects model. RESULTS: Five trials with 962 patients were included. In-segment minimum lumen diameter (MLD) was lower with DEB (standardized mean difference -0.24, 95% confidence interval [CI] -0.46 - -0.01) on angiographic follow-up at a mean of 8.6 months. There was no statistically significant difference in the risk of target vessel revascularization (TVR) at 1 year (RR 1.15, 95% CI 0.60-2.19), but TVR was increased with DEB at 3 years (RR 1.87, 95% CI 1.15-3.03). The risk of target lesion revascularization (TLR) was statistically increased with DEB (RR 2.17, 95% CI 1.13-4.19) at a mean of 24.4 months. There was no difference in the risk of MI, stent thrombosis, cardiac mortality and all-cause mortality between both groups. CONCLUSION: In patients with any type of ISR, DEB was associated a similar risk of TVR at 1-year, but increased risk of TVR and TLR at longer follow-up, as compared with EES. The quality of evidence was moderate, suggesting the need for further randomized trials with longer follow-up to confirm the role of DEB in the management of ISR.

Safety and efficacy of second-generation drug-eluting stents compared with bare-metal stents: An updated meta-analysis and regression of 9 randomized clinical trials.

The efficacy of second-generation drug-eluting stents (DES; eg, everolimus and zotarolimus) compared with bare-metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second-generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second-generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second-generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69-0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48-0.95), target-lesion revascularization (RR: 0.47, 95% CI: 0.42-0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41-0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38-0.80). The incidence of all-cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79-1.10). Meta-regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P < 0.0001, respectively). Compared with BMS, second-generation DES appear to be associated with a lower incidence of MACE, mainly driven by lower rates of target-lesion revascularization, MI, and stent thrombosis. However, all-cause mortality appears similar between groups.

Percutaneous coronary intervention or coronary artery bypass grafting for unprotected left main coronary artery disease.

BACKGROUND: Recent trials comparing PCI with CABG for unprotected left main disease yielded discrepant evidence. OBJECTIVES: To perform an updated meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease. METHODS: Randomized trials comparing PCI versus CABG for patients with unprotected left main coronary artery disease were included. Summary estimates risk ratios (RRs) were performed with a DerSimonian and Laird model at short-term, intermediate and long-term follow-up periods (i.e., 30-days, 1-year, and >1-year). Outcomes evaluated were major adverse cardiac and cerebrovascular events (MACCE), all-cause mortality, myocardial infarction, stroke, revascularization and stent thrombosis or symptomatic graft occlusion. RESULTS: Six trials with 4,700 patients and a mean SYNTAX score of 23 were included. At short-term follow-up, the risk of MACCE was lower with PCI (RR 0.55, 95% confidence interval [CI] 0.39-0.76) driven by the lower risk of myocardial infarction (RR 0.67, 95% CI 0.46-0.99), and stroke (RR 0.38, 95% CI 0.16-0.90). The risk of MACCE was similar at the intermediate follow-up (RR 1.21, 95% CI 0.97-1.51). At long-term follow-up, PCI was associated with a higher risk of MACCE (RR 1.19, 95% CI 1.01-1.41), due to a higher risk of revascularization (RR 1.62, 95% CI 1.34-1.94), while the risk of all-cause mortality, myocardial infarction, and stroke were similar. CONCLUSIONS: In patients with unprotected left main coronary disease and low to intermediate SYNTAX score, PCI might be an acceptable alternative to CABG. © 2017 Wiley Periodicals, Inc.

The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.

OBJECTIVE: To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients. BACKGROUND: Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions. METHODS: The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo. RESULTS: Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V02 max favored ADRCs (+45.4 ± 222 vs. -9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (-21.6 + 13.9 vs. -5.5 + 23.8, P = 0.038). CONCLUSIONS: A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.