Gérard Helft

Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial.

AIM This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following drug-eluting stent (DES) implantation. METHODS AND RESULTS Patients (N = 1799) who had undergone placement of ≥1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95). CONCLUSIONS Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment. CLINICALTRIALSGOV NUMBER NCT00822536.

Clinical outcome following coronary angioplasty in dialysis patients: a case–control study in the era of coronary stenting

BACKGROUND Balloon coronary angioplasty has been reported to be ineffective in patients treated for end stage renal disease because of a high restenosis rate. OBJECTIVE To compare the clinical outcome following coronary angioplasty with provisional stenting in dialysis versus non-dialysis patients. DESIGN A case–control study. PATIENTS Of 1428 consecutive patients who underwent coronary angioplasty, 100 (7%) were being treated for end stage renal disease. These were compared with 100 control patients matched for age, sex, coronary lesions, presence of diabetes mellitus, and rate of coronary stenting (40%). MAIN OUTCOME MEASURES In-hospital and one year clinical outcome. RESULTS The rates of procedural success (90% v 93%), in-hospital mortality (1% v 0%), stent thrombosis (0%v 0%), and Q wave myocardial infarction (0% v 1%) were similar in dialysis and non-dialysis patients. One year clinical outcome after coronary angioplasty was similar in the two groups in terms of clinical restenosis (31% v 28%) and myocardial infarction (6% v 2%), but cardiac death was more common in dialysed patients (11% v2%, p < 0.03). CONCLUSIONS Dialysis does not increase the risk of clinical restenosis after coronary angioplasty with provisional stenting. Coronary angioplasty is a safe and effective therapeutic procedure in selected dialysis patients with culprit lesions accessible to stenting. However, the one year survival is reduced in this high risk population.

Percutaneous coronary intervention in anticoagulated patients via radial artery access

Objectives: To assess safety and feasibility of using radial artery access for percutaneous coronary intervention (PCI) in patients on oral anticoagulation without interrupting therapy. Background: The radial artery approach for PCI is intuitively attractive for patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) but little data exist concerning feasibility or safety of this approach in this population. The main advantage of this strategy would be to avoid bridging therapy with heparin that increases risk of thrombotic and bleeding events. Methods: In this prospective observational study, 50 consecutive patients referred for coronary angiography underwent PCI without interrupting oral anticoagulant therapy. The main outcome measures were bleeding and thrombotic complications. Results: The indications for permanent oral anticoagulation were as follows: atrial fibrillation in 62%, mechanical prosthesis in 24%, and venous thromboembolism in 14%. Seventy‐two percent were elective cases and 28% presented with acute coronary syndromes. PCI was performed with an INR range of 1.4–3.4 with mean of 2.2 ± 0.6. Seventy‐six percent of the patients were on dual antiplatelet therapy before the procedure. No thrombotic events or excess bleeding were observed at 1 month. Only one patient had a minor hemorrhage 8 days after procedure. Conclusions: This series suggests that for patients treated with VKAs, the use of radial artery access is feasible and safe for PCI on dual antiplatelet therapy without interrupting oral anticoagulant treatment.

Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial

BACKGROUND Elderly patients regularly receive bare-metal stents (BMS) instead of drug-eluting stents (DES) to shorten the duration of double antiplatelet therapy (DAPT). The aim of this study was to compare outcomes between these two types of stents with a short duration of DAPT in such patients. METHODS In this randomised single-blind trial, we recruited patients from 44 centres in nine countries. Patients were eligible if they were aged 75 years or older; had stable angina, silent ischaemia, or an acute coronary syndrome; and had at least one coronary artery with a stenosis of at least 70% (≥50% for the left main stem) deemed eligible for percutaneous coronary intervention (PCI). Exclusion criteria were indication for myocardial revascularisation by coronary artery bypass grafting; inability to tolerate, obtain, or comply with DAPT; requirement for additional surgery; non-cardiac comorbidities with a life expectancy of less than 1 year; previous haemorrhagic stroke; allergy to aspirin or P2Y12 inhibitors; contraindication to P2Y12 inhibitors; and silent ischaemia of less than 10% of the left myocardium with a fractional flow reserve of 0·80 or higher. After the intended duration of DAPT was recorded (1 month for patients with stable presentation and 6 months for those with unstable presentation), patients were randomly allocated (1:1) by a central computer system (blocking used with randomly selected block sizes [two, four, eight, or 16]; stratified by site and antiplatelet agent) to either a DES or similar BMS in a single-blind fashion (ie, patients were masked), but those assessing outcomes were masked. The primary outcome was to compare major adverse cardiac and cerebrovascular events (ie, a composite of all-cause mortality, myocardial infarction, stroke, or ischaemia-driven target lesion revascularisation) between groups at 1 year in the intention-to-treat population, assessed at 30 days, 180 days, and 1 year. This trial is registered with ClinicalTrials.gov, number NCT02099617. FINDINGS Between May 21, 2014, and April 16, 2016, we randomly assigned 1200 patients (596 [50%] to the DES group and 604 [50%] to the BMS group). The primary endpoint occurred in 68 (12%) patients in the DES group and 98 (16%) in the BMS group (relative risk [RR] 0·71 [95% CI 0·52-0·94]; p=0·02). Bleeding complications (26 [5%] in the DES group vs 29 [5%] in the BMS group; RR 0·90 [0·51-1·54]; p=0·68) and stent thrombosis (three [1%] vs eight [1%]; RR 0·38 [0·00-1·48]; p=0·13) at 1 year were infrequent in both groups. INTERPRETATION Among elderly patients who have PCI, a DES and a short duration of DAPT are better than BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischaemia-driven target lesion revascularisation. A strategy of combination of a DES to reduce the risk of subsequent repeat revascularisations with a short BMS-like DAPT regimen to reduce the risk of bleeding event is an attractive option for elderly patients who have PCI. FUNDING Boston Scientific.

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:201Tl 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”.

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.

Safety and efficacy of vorapaxar in secondary prevention of atherosclerotic disease: A meta-analysis of randomized control trials

OBJECTIVE To study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. METHODS A systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction (MI), ischemic stroke and repeat revascularization. The pre-specified safety endpoint was intracranial hemorrhage (ICH) and a composite of TIMI major and minor bleeding. Risk ratios were used as the metric of choice by applying random effects models. RESULTS Five randomized controlled trials with 40,630 patients were included in final analysis. Compared with placebo, vorapaxar led to a statistically non-significant reduction in risk of MI [RR 0.86; 95% CI 0.80-0.93, p=0.427] and ischemic stroke [RR 0.84; 95% CI 0.72-0.97, p=0.920]. No differences were observed between vorapaxar and placebo with respect to all-cause mortality [RR 0.99; 95% CI 0.90-1.08, p=0.620], cardiovascular mortality [RR 0.94; 95% CI 0.83-1.06, p=0.351], repeat revascularization [RR 0.97; 95% CI 0.82-1.15, p=0.236], and TIMI bleeding [RR 1.29; 95% CI 0.98-1.69, p=0.126]. Vorapaxar was associated with a statistically non-significant higher risk of ICH [RR 2.36; 95% CI 1.40-3.96, p=0.137] compared with placebo. CONCLUSION Addition of Vorapaxar to standard medical therapy in in patients with atherosclerotic disease led to a statistically non-significant reduction in the risk of MI and ischemic stroke at the cost of statistically non-significant increase in risk of ICH.

Role of Vorapaxar After Coronary Revascularization

We aim to evaluate the potential benefit and risk of addition of vorapaxar to standard medical therapy in patients who underwent coronary revascularization with either percutaneous coronary revascularization or coronary artery bypass graft surgery. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials, and the clinical trial registry maintained at clinicaltrials.gov for randomized control trials evaluating the safety and efficacy of vorapaxar in patients who underwent coronary revascularization procedures with either percutaneous coronary revascularization or coronary artery bypass graft surgery. Event rates were compared using a Forest plot of relative risk using a random-effects model. The 5 studies (n = 24,025) that met all criteria were included in the final analysis. After coronary revascularization procedures, addition of vorapaxar to standard medical therapy was associated with reduction in the risk of myocardial infarction (MI; risk ratio 0.83 [0.75 to 0.92]) and ischemic stroke (0.011 [0.007 to 0.016]); however, it also resulted in significant increase risk of hemorrhagic stroke (1.57 [1.01 to 2.44]) and Thrombolysis In Myocardial Infarction major and minor bleeds (1.36 [1.07 to 1.70]). There was no significant difference in the risk of cardiovascular mortality (0.90 [0.73 to 1.09]), repeat revascularization (0.78 [0.23 to 2.70]), and stent thrombosis (0.95 [0.62 to 1.45]) in the vorapaxar and control groups. In conclusion, after coronary revascularization procedures, addition of vorapaxar to standard medical therapy was associated with reduction in the risk of MI and ischemic stroke and increase in risk of hemorrhagic stroke and Thrombolysis In Myocardial Infarction major and minor bleeds.

Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction in Nonagenarians: A Multicenter Study

Memantine has a long elimination half-life of approximately 70 hours, which results in little peak-to-trough concentration variations between doses at steady state (after 2 weeks of therapy). The soon-to-be-discontinued memantine tablets have been given once daily, which can promote medication adherence and appears to be well tolerated. Newly marketed memantine XR capsules also offer convenient once-daily dosing, but with the unavailability of standard memantine tablets, patients will have no option but to take XR capsules unless the more-expensive oral solution formulation is prescribed. Forest Laboratories has priced memantine XR at a 5% discount to the wholesale acquisition cost of standard tablets, but the discontinuation of standard tablets has been viewed as a marketing strategy. This analysis suggests that the currently recommended dosing transition may result in a significant increase in steady state peak and trough levels. Based on these pharmacokinetic calculations, practitioners might consider transitioning these patients first to 21 mg XR once daily before escalating to 28 mg. Similarly, this analysis suggests that the recommended dosing transition in individuals with severe renal impairment will also result in significant plasma concentration increases. This analysis was conducted based on population pharmacokinetic parameters, but the data are consistent with the limited data on file from the manufacturer. Pharmacokinetic studies comparing standard tablets with XR formulations are necessary to validate the theoretical construct. Nevertheless, clinicians should monitor patients for adverse drug reactions after the manufacturer-recommended switch from standard tablet to XR because total daily drug dose will be approximately 40% greater. In a 24-week clinical study, memantine XR was well tolerated, with the most common side effects being headache (5.6%) and diarrhea (5.0%). Postmarketing surveillance data are awaited to evaluate the side-effect profile with its longterm use. Whether higher drug exposure will enhance drug effects on cognition remains to be seen but will probably never be elucidated in controlled trials because no comparative studies between 10 mg twice daily and 28 mg XR once daily have been performed.