Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey.

BACKGROUND: Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. METHODS: The data for all consecutive patients hospitalized in 2012-2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0-2) (n = 234) after matching for age, sex, and diabetes (1:2). RESULTS: Although LDL-cholesterol was high (208 [174-239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090-3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014-1.057, P = 0.001). CONCLUSIONS: FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial.

BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI. METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290. FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070). INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI. FUNDING: ACTION Study Group and AstraZeneca.

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study.

BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Prevalence, risk factor burden, and severity of coronary artery disease in patients with heterozygous familial hypercholesterolemia hospitalized for an acute myocardial infarction: Data from the French RICO survey.

BACKGROUND: Individuals with heterozygous familial hypercholesterolemia (FH) are at high risk of early myocardial infarction (MI). However, coronary artery disease (CAD) burden of FH remains not well described, especially for French patients. OBJECTIVE: The objective of this study was to assess the prevalence of FH and severity of CAD from a large database of a French regional registry of acute MI. METHODS: All consecutive patients hospitalized for an acute MI in a multicenter database from 2001 to 2017 were considered. FH was diagnosed using an algorithm adapted from the Dutch Lipid Clinic Network criteria. The prevalence and clinical features of FH and the severity of CAD were assessed. RESULTS: Among the 11,624 patients included in the study, the proportion of "probable/definite", "possible", and "unlikely" FH in patients with MI was 2.1% (n = 249), 20.7% (n = 2405), and 77.2% (n = 8970), respectively. When compared with patients with "unlikely" FH, patients with "probable/definite" FH were 20 years younger (51 vs 71, P < .001), with a lower rate of diabetes (17% vs 25%, P = .007) and a higher prevalence of personal and familial history of CAD. Chronic statin treatment was only used in 48% of FH patients and ezetimibe in 8%. After adjustment for age, sex, and diabetes, patients with FH were characterized by increased extent of CAD (SYNTAX score 11 vs 7, P < .001) and multivessel disease (55% vs 40%, P < .001). CONCLUSIONS: In this large cohort of French individuals, FH was common in patients with MI, associated with markedly early age of MI and severity of CAD burden and limited use of preventive lipid-lowering therapy.

N-Terminal Fragment of Pro B-type Natriuretic Peptide as a Marker of Contrast-Induced Nephropathy After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is frequent and associated with long-term renal impairment and mortality. Early markers of CIN are needed to improve risk stratification. We aimed to assess whether N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) could be associated with CIN. From the French regional RICO survey, all the consecutive patients who underwent primary PCI for STEMI, from January 1, 2001, to December 3, 2013, were included. Nt-proBNP circulating levels were assessed on admission. CIN was defined as an increase in serum creatinine >26.5 µmol/L or >50% within 48 to 72 hours after PCI (KDIGO criteria). Of the 1,243 patients included, CIN occurred in 130 patients (10.4%). Nt-proBNP levels were 5 times greater in patients who developed CIN than without CIN (1,275 [435 to 4,022] vs 247 [79 to 986] pg/mL, p <0.001). Hospital mortality rate was markedly higher in patients with CIN (6.9% vs 1.1%, p <0.001). Nt-proBNP levels were univariate predictors for CIN as were age, hypertension, diabetes, smoking, previous stroke, heart rate, impaired left ventricular ejection fraction C-reactive protein, history of renal failure, anemia, and estimated glomerular filtration rate <30 ml/min/1.73 m(2) at baseline. Nt-proBNP levels remained strongly associated with the occurrence of CIN even after adjustment for risk factors, treatments, clinical and biological variables (odds ratio 1.99, 95% confidence interval 1.49 to 2.66). Net reclassification improvement was achieved by the addition of Nt-proBNP to the risk model (p = 0.003). In conclusion, from this large contemporary prospective study in nonselected population, our work suggests that Nt-proBNP levels at admission could help to identify patients at risk of CIN beyond traditional risk factors.

The Log book for the secondary prevention of coronary artery disease: A pilot study.

INTRODUCTION: In secondary prevention (SP) of coronary artery disease (CAD), in particular after an acute myocardial infarction (MI), a better knowledge and self-management by the patient may have various supports. The Log book (LB) for CAD patients in Côte d'Or, was created in 2010 by a multidisciplinary team of healthcare professionals of Côte d'Or, from a regional care network. This pilot study evaluated LB as novel support for SP after acute MI. METHODS: A prospective study on 183 patients hospitalised for an acute MI in the region of Côte d'Or from 1st May to 30th October 2010. Patients were randomized in 91 patients who received an LB at the time of their hospitalisation (LB+ group), and 92 patients who were not given an LB (LB- group). The follow up (FU) was performed at 4 months and 1 year. RESULTS: Baseline characteristics were similar in the 2 groups, except for smoking, which was more frequent in the LB-group than in the LB+ group. At FU, LB was usually well accepted by both patients and their general practitioners (GP). At 4 months FU, the patients LB+ were more prone to see their general practitioners than patients LB- (100% vs 85% in the LB- group, P=0.007). Moreover, in LB+ group, there was a trend towards a more frequent physical activity, including exercise bike (P=0.009) and an increase in HDL-cholesterol (HDL-c) (P=0.165). At 1 year FU, body mass index from LB+ was more reduced than in patients LB- (P=0.029). Finally, there was a trend towards lower morbi-mortality (hospitalisation for cardiovascular cause or death) in the LB+ group than in the LB- group (11 vs 22%, P=0.083). CONCLUSION: This pilot study showed the feasibility of LB as a support for SP and its interest in post MI management in a local care network setting. In addition, our study provides encouraging data on the potential benefits of this pioneer tool for SP.

Initial and follow-up results of the European Seaquence coronary stent registry.

The primary objective of the present study was to assess the feasibility and the safety of the Seaquence stent (CathNet-Science) deployment for the treatment of coronary artery disease and the event-free survival of patients treated with this coronary stent. The study was conducted as a multicenter, prospective, observational registry. Patients with stable or unstable angina pectoris who were candidates for percutaneous coronary intervention with elective stenting of one single de novo lesion in a native coronary artery > or =3 mm in diameter were included in the study. Clinical follow-up was performed at 1 month and 9 months. Major adverse coronary events (MACE), that is, cardiac death, myocardial infarction, and target vessel revascularization (re-PTCA or CABG), were recorded over a period of 9 months. Using this stent, a 99% in-hospital success rate was achieved. A total of 17 patients presented MACE (8.7%) during the whole follow-up period and target lesion revascularization was needed for 14 (7.1%) patients. Using multivariate analysis only some clinical parameters (patients treated for unstable angina, with a history of CABG or of female gender) were found as independent predictors of MACE after coronary stenting. Procedural related factors, angiographic characteristics, or reference diameter were not found to influence clinical outcome. Because the study was performed in patients with a high proportion of complex lesions (relative high-risk nonselected population with nearly one third calcified lesions, many long and type B2 and C lesions) we can conclude that the coronary Seaquence stent can be considered as a stent of reference in routine practice.