Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

AIMS We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Good reproducibility of heart rate variability after orthostatic challenge in patients with a history of acute coronary syndrome

BACKGROUND: Several parameters of heart rate variability (HRV) have been shown to predict the risk of sudden cardiac death (SCD) in cardiac patients. There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge. For the first time, we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome. METHODS: Sixty male patients (65+/-8years) with a history of acute coronary syndrome on stable medication were included. HRV was measured in supine (5min) and standing (5min) position on 2 occasions separated by two weeks. For risk assessment relevant time-domain [standard deviation of all R-R intervals (SDNN) and root mean squared standard differences between adjacent R-R intervals (RMSSD)], frequency domain [low-frequency power (LF), high-frequency power (HF) and LF/HF power ratio] and short-term fractal scaling component (DF1) were computed. Absolute reproducibility was assessed with the standard errors of the mean (SEM) and 95% limits of random variation, and relative reproducibility by the intraclass correlation coefficient (ICC). RESULTS: We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test. All ICCs were good to excellent (ICCs between 0.636 and 0.869). CONCLUSIONS: Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position.

Synchronous carotid and coronary bypass surgery using minimal extracorporeal circulation does not increase the risk of in-hospital stroke compared to isolated carotid endarterectomy under general anaesthesia

Gebiet: Chirurgie Abstract: Introduction: Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) could be approached in a combined or a staged fashion. Some crucial studies have shown no significant difference in peri-operative stroke and death rate in combined versus staged CEA/CABG. At present conventional extracorporeal circulation (CECC) is regarded as the gold standard for performing on-pump coronary artery bypass grafting. On contrary, the use of minimized extracorporeal circulation (MECC) for CABG diminishes hemodilution, blood-air contact, foreign surface contact and inflammatory response. At the same time, general anaesthesia (GA) is a potential risk factor for higher perioperative stroke rate after isolated CEA, not only for the ipsilateral but also for the contralateral side especially in case of contralateral high-grade stenosis or occlusion. The aim of the study was to analyze if synchronous CEA/CABG using MECC (CEA/CABG group) allows reducing the perioperative stroke risk to the level of isolated CEA performed under GA (CEA-GA group). – Methods: A retrospective analysis of all patients who underwent CEA at our institution between January 2005 and December 2012 was performed. We compared outcomes between all patients undergoing CEA/CABG to all isolated CEA-GA during the same time period. The CEA/CABG group was additionally compared to a reference group consisting of patients undergoing isolated CEA in local anaesthesia. Primary outcome was in-hospital stroke. – Results: A total of 367 CEAs were performed, from which 46 patients were excluded having either off-pump CABG or other cardiac surgery procedures than CABG combined with CEA. Out of 321 patients, 74 were in the CEA/CABG and 64 in the CEA-GA group. There was a significantly higher rate of symptomatic stenoses among patients in the CEA-GA group (p<0.002). Three (4.1%) strokes in the CEA/CABG group were registered, two ipsilateral (2.7%) and one contralateral (1.4%) to the operated side. In the CEA-GA group 2 ipsilateral strokes (3.1%) occurred. No difference was noticed between the groups (p=1.000). One patient with stroke in each group had a symptomatic stenosis preoperatively. – Conclusions: Outcome with regard to mortality and neurologic injury is very good in both -patients undergoing CEA alone as well as patients undergoing synchronous CEA and CABG using the MECC system. Although the CEA/CABG group showed slightly increased risk of stroke, it can be considered as combined treatment in particular clinical situations.

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction.

AIMS Our aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial. METHODS AND RESULTS The BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis. CONCLUSIONS In this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey

AIMS Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. METHODS AND RESULTS A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. CONCLUSIONS The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

Intracoronary imaging of coronary atherosclerosis: validation for diagnosis, prognosis and treatment.

While coronary atherosclerosis is a leading cause of mortality, evaluation of coronary lesions was previously limited to either indirect angiographic assessment of the lumen silhouette or post mortem investigations. Intracoronary (IC) imaging modalities have been developed that allow for visualization and characterization of coronary atheroma in living patients. Used alone or in combination, these modalities have enhanced our understanding of pathobiological mechanisms of atherosclerosis, identified factors responsible for disease progression, and documented the ability of various medications to reverse the processes of plaque growth and destabilization. These methodologies have established a link between in vivo plaque characteristics and subsequent coronary events, thereby improving individual risk stratification, paving the way for risk-tailored systemic therapies and raising the option for pre-emptive interventions. Moreover, IC imaging is increasingly used during coronary interventions to support therapeutic decision-making in angiographically inconclusive disease, guide and optimize procedural results in selected lesion and patient subsets, and unravel mechanisms underlying stent failure. This review aims to summarize current evidence regarding the role of IC imaging for diagnosis and risk stratification of coronary atherosclerosis, and to describe its clinical role for guiding percutaneous coronary interventions. Future perspectives for in-depth plaque characterization using novel techniques and multimodality imaging approaches are also discussed.

Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Causes of late mortality with dual antiplatelet therapy after coronary stents.

AIMS In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study. METHODS AND RESULTS Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% (P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% (P = 0.01) over the randomized period (Months 12-30). Rates of fatal bleeding were 0.2 vs. 0.1% (P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% (P = 0.36), Months 12-33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% (P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% (P = 0.16). CONCLUSION Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00977938.

Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients.

OBJECTIVES The purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. BACKGROUND New-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD. METHODS Patient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11). RESULTS A total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR pint = 0.059; ST pint = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (pint = 0.042). CONCLUSIONS New-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.