Optimal long-term antithrombotic treatment of patients with stable coronary artery disease and atrial fibrillation: "OLTAT registry".

BACKGROUND: The optimal long-term antithrombotic treatment of patients with stable coronary artery disease (CAD) and atrial fibrillation (AF) is a challenge in daily practice. We sought to determine the prevalence of hemorrhagic complications and ischaemic events depending on antithrombotic strategy in patients with stable CAD and AF. METHODS: The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of cardiovascular mortality, myocardial infarction and ischaemic stroke. The subsequent risks of MACCE and clinically significant bleedings requiring hospitalisation (major safety outcome) were analyzed in a propensity score-matched analysis by adjusted Cox regression models. RESULTS: Six hundred and six patients with high thrombotic and bleeding risks (mean age 73.4 ±â€¯9.8 years, 25.2% female, CHA2DS2-VASc score:4.7 ±â€¯1.5, and HAS-BLED score:3.1 ±â€¯1.0) were included, and 127 propensity-matched pairs were analyzed. At inclusion, 172 patients (28.4%) were on oral anticoagulation (OAC) alone (75.6% on VKA and 24.4% on DOAC) and 434 patients (71.6%) on OAC + single antiplatelet therapy (SAPT) (71.9% on VKA and 28.1% on DOAC). At 5-year follow-up, MACCE rate did not significantly differ in both groups (30.9% in OAC + SAPT vs. 26.8% in OAC alone; adjusted HR 1.1 [0.8-1.5], p = 0.58), but clinically significant bleedings (28.3% vs. 18.5%; adjusted HR 1.8 [1.2-2.8], p = 0.005) and total deaths (29.5% vs. 20.8%; adjusted HR 1.4 [95% CI 1.0-2.2], p = 0.049) were higher in patients with OAC + SAPT than in patients with OAC alone. CONCLUSIONS: In patients with stable CAD and AF, the addition of antiplatelet therapy to VKA or DOAC therapy was independently associated with a higher risk of bleeding and overall mortality, without significant reduction in cardiac and cerebral ischaemic events.

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: the DIABHYCAR prospective study.

AIM: Vitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients. METHODS: A cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI). RESULTS: In the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05-1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02-1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03-1.73; P = 0.03). CONCLUSION: The haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.

A randomized study comparing isotope and echocardiography stress testing in the screening of silent myocardial ischaemia in type 2 diabetic patients.

AIMS: This study aimed to compare the positive predictive value (PPV) of stress myocardial scintigraphy (SPECT) and of dobutamine echocardiography (DE) in the diagnosis of significant coronary artery stenosis (CAD) in asymptomatic type 2 diabetic patients, and to assess long-term clinical outcomes according to silent myocardial ischaemia (SMI) screening. METHODS: A total of 204 asymptomatic type 2 diabetic patients at high cardiovascular (CV) risk were prospectively randomized to undergo either SPECT (n=104) or DE (n=100). Coronary angiography was proposed in cases of SMI, with revascularization of suitable lesions. Intensive treatment of CV risk factors was prescribed for all patients. Death and myocardial infarction (MI) were recorded during the 3-year follow-up. RESULTS: Clinical characteristics were similar in the two testing groups. The prevalence of SMI and significant CAD were 13% and 4%, respectively, in the SPECT group vs 11% and 5%, respectively, in the DE group (not significant [NS]). The PPV for the detection of significant CAD was 29% for SPECT and 45% for DE (NS). Seven patients (3%) underwent initial revascularization. The 3-year rate of CV death and MI was 2.5%, and similar in both groups. CONCLUSION: Rates of SMI and significant CAD in asymptomatic high-risk type 2 diabetic patients receiving intensive care of risk factors are low, and SPECT and DE are similar in the detection of SMI and CAD. Coronary revascularization and intensive CV risk-factor therapy are associated with a low rate of adverse CV events at 3 years, whichever stress test was used.

Characteristics and prognosis of patients with angiographic stent thrombosis: comparison between drug-eluting and bare-metal stents.

INTRODUCTION: Conflicting data exist on the risk of stent thrombosis with drug-eluting stents (DES) versus bare-metal stents (BMS). Little is known about the potential different characteristics and outcomes of DES versus BMS thrombosis. OBJECTIVE: To compare the characteristics, timing and outcomes of patients with angiographic stent thrombosis according to type of stent implanted. METHODS: The population comprised consecutive patients who underwent BMS or DES implantation (January 2003-April 2007) at Pitié-Salpêtrière Hospital. Data from patients with and without a stent thrombosis were compared to identify predictors of thrombosis. Timing of thrombosis (acute,<24 hours; subacute,<30 days; late,>30 days; very late,>1 year), clinical, angiographic and procedural characteristics, and outcomes were compared between patients with a BMS or DES thrombosis. RESULTS: A total of 3579 patients received a BMS (2815 lesions, 2318 patients) or a DES (1536 lesions, 1261 patients). Documented angiographic stent thrombosis occurred in 52 (1.4%) patients, 16 (1.3%) with a DES and 36 (1.6%) with a BMS. Rates of acute (0.1% versus 0.2%), subacute (1% versus 0.7%), late (both 0.2%) and very late (both 0.2%) thrombosis were similar in patients with BMS and DES thrombosis. Factors predictive of stent thrombosis were similar, including left ventricular failure (P<0.0001), initial percutaneous coronary intervention (PCI) for acute myocardial infarction (P<0.0001), multivessel PCI (P<0.0001), and balloon dilatation before stenting (P<0.04). Eleven (21%) cases of BMS (n=8, 22%) or DES (n=3, 19%) thrombosis arose soon after stopping antiplatelet therapy. Thirteen of 52 (25%) patients died a few hours after the event. Twenty-seven (52%) major adverse cardiac events occurred at 18 months, 7 in patients with a DES and 20 in those with a BMS (44% versus 55%, P=NS). These included 16 deaths (31%), 7 repeat PCIs and 4 myocardial infarctions. There were no independent predictive factors of death after stent thrombosis. CONCLUSIONS: BMS and DES thrombosis are similar in terms of timing of thrombosis, characteristics and outcomes, and share the same risk of late thrombosis after interruption of antiplatelet therapy.

Medium-term survival after primary angioplasty for myocardial infarction complicated by cardiogenic shock after the age of 75 years.

AIMS OF THE STUDY: To assess mortality in people > or =75 years of age 6 months after myocardial infarction complicated by cardiogenic shock and treated by angioplasty with complete revascularisation and optimal anti-thrombotic treatment; to compare results to those of younger patients with or without shock and to analyse predictive factors for death. MATERIALS AND METHODS: The study is based on 1011 consecutive patients with myocardial infarction admitted for primary angioplasty, subdivided into four groups by age and the presence or absence of cardiogenic shock: group 1 (<75 years of age without shock, n=733), group 2 (<75 years of age with shock, n=49), group 3 (> or =75 years of age without shock, n=208) and group 4 (> or =75 years of age with shock, n=20). These four patient groups were compared for mortality rates and predictive factors for in-hospital and 6 month mortality. RESULTS: In-hospital mortality in groups 1 to 4 was 1.7%, 30.6%, 9.1%, and 70% (p<0.0001) respectively and 6-month mortality was 3.1%, 40%, 16% and 78% (P<0.0001). By univariate analysis renal failure was a predictive factor for death at 6 months in patients without cardiogenic shock (groups 1 and 3), and left ventricular function in patients in group 2. No predictive factors were found in group 4 patients. The independent predictive factors for death at 6 months were: age >75 years of age (P<0.0003), cardiogenic shock (P<0.0001), triple vessel lesions (P<0.01) and creatinine clearance (P=0.004). CONCLUSION: Mortality after angioplasty remains high in people > or =75 years with cardiogenic shock despite all the advances in the management of myocardial infarction. These disappointing results should encourage us to assess the role of surgical revascularisation and circulatory assistance.

[The value of active stents for coronary angioplasty in patients with chronic renal failure]. / Intérêt du stent actif dans l'angioplastie coronaire chez l'insuffisant rénal chronique.

UNLABELLED: The risk of intra-stent restenosis has diminished considerably with the advent of endoprostheses which actively release sirolimus or paclitaxel. Patients with chronic renal failure constitute a high cardiovascular risk population, in whom the incidence of coronary heart disease is particularly high, representing one of the principal causes of death. The aim of this study, which included 152 patients, was to quantify the value of active stents for coronary angioplasty in patients with chronic renal failure. Thirty eight patients with chronic renal failure who underwent angioplasty with active stents were matched for age, sex and the presence of diabetes with 3 other groups of patients: one group with active stents but without renal failure, one group with inactive stents and no renal failure, and one group with inactive stents and chronic renal failure. The average follow up was 16 +/- 5 months. The acute stent thrombosis rate (2%) was not elevated in cases of renal failure nor after active stent implantation. Chronic renal failure significantly increased the mortality rate 16 months after angioplasty, whichever type of stent was used: 8 versus 2% deaths in patients with an inactive stent (p = 0.001). In renal failure, the risk of death was lower with an active stent (8 vs 26% with an inactive stent, p<0.05). Similarly, there was a non-significant trend towards a lower risk of death and/or infarction in renal failure after active stents (8 vs 21% with an inactive stent, NS). CONCLUSIONS: In this study, coronary angioplasty with an active stent in patients with chronic renal failure was associated with a lower mortality rate compared with inactive stents, with no increase in the risk of acute thrombosis.

Active stents in diabetic patients.

In the treatment of coronary stenosis, evolution after PTCA is not as good in diabetic patients compared to non diabetic ones, whatever the treatment used. We now have data of large clinical studies which show good results of drug loaded stents in diabetic patients, especially with either a cytostatic drug (sirolimus) or a cytotoxic one (paclitaxol). In the RAVEL study, among the 44 diabetic patients, 19 had sirolimus stenting with a restenosis rate of 0% vs a restenosis rate of 40% for the 25 patients with standard stents. In the 279 diabetic patient group of the SIRIUS study, the restenosis rate (50% or more stenosis rate) was 17.6% when sirolimus stenting was used vs 50.5% for the patients with standard stenting and at 9 months and target lesion revascularisation was from 22.3% with bare metal stents, compared to 6.9% with sirolimus eluting stents. In the TAXUS IV study, the advantage was evident in diabetic patients with a restenosis rate 80% lower in patients treated with oral anti diabetic therapy and 82% in patients treated with insulin. In the TAXUS VI study, the target lesion revascularisation rate of diabetic patients was 2.6% when taxus MR (modified release) was used, vs 22.6% with standard stents. The event which until now made PTCA different from surgery was restenosis, especially in diabetic patients. The analysis of use of recent active stenting registries has shown that diabetic patients have now much better long term results than previously reported.

Cumulative adverse effects of diabetes mellitus and hypertension on coronary flow velocity reserve.

BACKGROUND: this study aimed to assess the hypothesis that essential hypertension (EH) may increase coronary microcirculation dysfunction in patients with type 2 diabetes mellitus (DM). Microvascular dysfunction has been reported in patients with DM or EH. Discordant results have been reported on cumulative adverse effects of the simultaneous presence of DM and EH on coronary flow velocity reserve (CFR). METHODS: CFR were compared in 13 hypertensive diabetics (group 1), 12 normotensive diabetics (group 2), 11 hypertensive non diabetics (group 3) and 29 normotensive non diabetic patients (group 4). CFR was calculated using an intracoronary Doppler-tipped flow wire. RESULTS: CFR was significantly lower in patients with both DM and EH (2.2 +/- 0.4 in group 1 vs 2.8 +/- 0.5, 2.8 +/- 0.6 and 2.9 +/- 0.7 in groups 2, 3 and 4 respectively, p<0.01). The presence of hypertension reduced CFR in diabetic patients with angiographically abnormal but unobstructed coronary arteries (2.1 +/- 0.3 in hypertensive vs 3.1 +/- 0.2 in normotensive diabetic patients, p<0.02). No cumulative adverse effect was observed in diabetics with angiographically normal coronary arteries (2.3 +/- 0.6 in hypertensive vs 2.6 +/- 0.5 in normotensive diabetic patients, NS). Multivariate analysis revealed that combination of DM and EH (p<0.007) was independently related to CFR. CONCLUSIONS: the presence of hypertension appears to worsen coronary microangiopathy in diabetic patients with unobstructed coronary artery disease. The cumulative effect of EH and DM on CFR impairment has consequences for decision-making during coronary angioplasty and could identify patients at risk for cardiomyopathy.

[Heart, diabetes and glitazones]. / Coeur, Diabète et Glitazones.

Beneficial metabolic effects of rosiglitazone are now well established and its adverse events, generally minor or mild well known too. Following a brief review of these metabolic effects and main adverse events, we mainly describe fluid retention (and edema) and the heart failure risk, their risk factors, clinical and diagnosis characteristics, possible pathophysiological mechanisms and the main preventive measures are reviewed. Numerous experimental data and/or preliminary studies in type 2 diabetic patients, including effects on cardiovascular risk factors or markers, justify to conduct a large prospective long term clinical program to assess rosiglitazone effects on cardiovascular morbidity and mortality in type 2 diabetic patients at high cardiovascular risk, these studies are briefly described.

[Thrombosis caused by active rapamycin stents]. / Thrombose de stents actifs à la rapamycine.

We report the case history of a patient aged 68 years presenting with a recurrence of anterior myocardial infarction complicated by cardiogenic shock with a thrombosis of an active rapamycin stent 77 days following the angioplasty procedure. This was provoked by stopping platelet anti-aggregant treatment, a diabetic background and in the context of scheduled surgery for cancer recurrence. Recent data in the literature combined with our observations prompt the continuation of anti-aggregant bi therapy for at least 9 months after endoprosthesis insertion even if an active stent is used. In the case where surgery is envisaged, it is necessary to wait at least 6 months after the rapamycin stent revascularisation procedure. If an extra-cardiac procedure is envisaged during the angioplasty, it would be preferable to not use an active stent.

[Specificity of the management of atheromatous disease in diabetic renal failure]. / Spécificité de la prise en charge des localisations athéromateuses chez le diabétique insuffisant rénal.

Atheromatous disease is particularly common and severe in diabetics with renal failure. The prognosis depends on specific therapeutic measures: in this article, the authors will limit the discussion to the management of coronary artery disease. The cardiovascular risk factors must be treated intensively and corrected. The outlook of these patients also depends on the diagnosis of silent ischaemia with a stress test every two years and the prevention of acute renal failure after coronary angiography. Myocardial revascularisation improves the prognosis of high risk coronary patients. The choice of mode of revascularisation depends on the anatomy of the coronary lesions, the surgical risk and the presence of associated valve disease. The results of coronary angioplasty have been improved by the optimisation of anti-thrombotic treatment and the use of active stents. Despite revascularisation, short and medium-term mortality remains much higher than that of non-diabetics with normal renal function. Non-invasive investigations for residual ischaemia are justified 6 months after angioplasty for diagnosing restenosis and, thereafter, every year to detect progression of the atherosclerosis.

[Non cardiac surgery in patient with coronary stenting: think sirolimus now!]. / Chirurgie générale et endoprothèse coronaire: pensez au sirolimus!

We describe a severe preoperative cardiogenic shock in a patient scheduled for a breast surgery. The cardiogenic shock was in relation with thrombosis of two sirolimus-eluting stents received 3 months ago. A percutaneous transluminal coronary angioplasty was successfully performed. The patient recovered well after a 1-day treatment including intraaortic balloon counter pulsation and dobutamine infusion. We discuss about the ideal timing to plan surgery and how to manage the shift of antiplatelet agents.

[Clopidogrel and thrombopenia. A case report]. / Clopidogrel et thrombopénie. A propos d'un cas.

We report our experience with a case of isolated profound thrombocytopenia after clopidogrel (thienopyridine) administration. No adverse event such as bleeding or thrombotic event had occurred, although clopidogrel has been discontinued two weeks after the coronary artery stenting. Despite the safety of clopidogrel, this case demonstrates that clopidogrel can be associated not only with thrombotic thrombocytopenic purpura but also with isolated thrombocytopenia.

Myocardial viability, coronary flow reserve, and in-hospital predictors of late recovery of contractility following successful primary stenting for acute myocardial infarction.

OBJECTIVE: To assess the relation between myocardial viability, coronary flow reserve, and recovery of myocardial contractility after stenting for acute myocardial infarction. DESIGN: Consecutive sample prospective study. SETTING: University hospital. PATIENTS: 41 patients with single vessel disease and successful primary stenting for a first acute myocardial infarction. INTERVENTIONS: (201)Tl single photon emission computed tomography, contrast ventriculography, and intracoronary Doppler performed 7 (1) days after primary stenting. MAIN OUTCOME MEASURES: Regional contractility recovery assessed by contrast ventriculography at 6 (1) months' follow up. RESULTS: On univariate analysis, contractility recovery was correlated to prereperfusion anterograde and collateral flow grades (r = 0.41, p = 0.03 and r = 0.55, p = 0.0004), viability index (r = 0.55, p = 0.04), peak creatine kinase concentrations (r = -0.55, p = 0.0005), left ventricular ejection fraction (r = 0.45, p = 0.005), end diastolic pressure (r = -0.62, p < 0.0001), end systolic volume index (r = -0.47, p = 0.01), and the extent of hypokinetic area (r = -0.48, p = 0.003), but not the coronary flow reserve. On multivariate analysis, independent predictors of late contractility recovery were prereperfusion anterograde and collateral flow grades and viability index. Relative coronary flow reserve, reflecting the culprit vessel's microvascular function, was correlated only to the extent of the infarct risk area (r = -0.45, p = 0.003). CONCLUSIONS: Independent predictors of contractility recovery between the seventh day and the sixth month after successful stenting for acute myocardial infarction are prereperfusion anterograde and collateral flows and myocardial viability. The culprit vessel's microvascular dysfunction is independent of myocardial viability and contractility and correlated to the extent of "jeopardised microvasculature".

[Absence of nephro-protective effect of acetylcysteine in patients with chronic renal failure investigated by coronary angiography]. / Absence d'effet néphroprotecteur de l'acetylcystéine chez les patients avec insuffisance rénale chronique explorés par coronarographie.

Recent studies have suggested that an oral dose of acetylcysteine could play a prophylactic role in the prevention of nephrotoxicity from iodine contrast media in patients affected by chronic renal failure. Between June 2001 and September 2002 we selected 120 patients with a basal plasma creatinine level greater than 1.36 mg/dl investigated by coronary angiography. The treatment group included 60 patients who received 600 mg of acetylcysteine in the morning and evening before the day of the examination together with intravenous saline hydration. The control group patients received hydration alone. The clinical characteristics of the groups were comparable as well as the basal plasma creatinine level: 2.01+/-1.1 mg/dl in the acetylcysteine group and 1.81+/-0.69 in the control group. The plasma creatinine level was measured 24 and 48 hours after coronary angiography. The respective changes in plasma creatinine level at 24 and 48 hours were 0.12+/-0.29 and 0.02+/-0.29 mg/dl in the acetylcysteine group and 0.06+/-0.29 and 0.07+/-0.43 mg/dl in the control group (NS). Acute renal failure caused by the contrast medium, defined by an increase of 25% in the plasma creatinine level compared to the basal value, occurred in 3 patients from the acetylcysteine group and 2 patients from the control group. The only predictive factor for acute renal failure was the quantity of contrast medium (316+/-141 vs 173+/-115 ml, p<0.05). In conclusion, acute renal failure caused by contrast medium is rare in sufficiently hydrated patients with moderate chronic renal failure when a low dose of contrast medium is used. Our study does not confirm a prophylactic effect of acetylcysteine in the prevention of nephrotoxicity from contrast media following coronary angiography in patients with moderate chronic renal failure.

[Value of combined coronary angioplasty and coronary angiography]. / Intérêt de l'angioplastie coronaire dans le même temps que la coronarographie.

Combined coronary angioplasty and coronary angiography is performed in most catheter laboratories and has become a routine procedure. The aim of this study was to assess its clinical results and economic value. This was a retrospective monocenter study performed over an 11 year period (1990-2000) which included 2,727 patients requiring coronary angioplasty after coronary angiography. The angioplasty procedure was performed at the same time as angiography (combined, n = 1,809) or after angiography (deferred, n = 631). Patients admitted for acute coronary syndromes not stabilised by pharmacological interventions were excluded from the study. The comparison of these two modes of angioplasty was based on primary success rates, complications, duration of hospital stay and hospital costs. The combined procedure was used progressively more frequently over the study period, increasing from 54% to 88% in 2000. The hospital clinical results (Success and complication rates) were comparable in the two groups. The predictive factors of failure were the year of the angioplasty procedure and occlusive lesions on multivariate analysis. The combined procedure was associated with a shorter hospital stay than deferred angioplasty (8.2 +/- 6.1 days versus 15.0 +/- 8.0 days, p = 0.0001) and with lower costs. The authors conclude that combined coronary angiography-angioplasty is as effective and as safe as deferred angioplasty. It is associated with a shorter hospital stay and lower hospital costs.

[Mediastinal tumor revealed by myocardial infarction]. / Tumeur médiastinale révélée par un infarctus du myocarde.

We report the case of a patient with a past history of coronary atherosclerosis treated with primary angioplasty 5 hours following an inferior myocardial infarction. Echocardiography performed during the procedure revealed a mediastinal tumour invading the tricuspid, responsible for the occlusion of the right coronary. Infarction due to tumour compression is a rare presentation of mediastinal tumour. Diagnosis relies on echocardiographic, CT or magnetic resonance imaging. The prognosis is linked to the tumour pathology.