Philippe Commeau

Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation

We carried out a prospective evaluation of a new vasodilator‐stimulated phosphoprotein (VASP) phosphorylation assay in order to detect patients with high‐risk coronary subacute stent thrombosis (SAT) despite thienopyridine regimen. Twenty healthy donors (group 1) without any medication were compared to 16 stented patients (group 2) treated by ticlopidin or clopidogrel initiated 2 days before stenting and aspirin (250 mg/day). No difference in platelet reactivity was noted between group 1 and group 2 treated only with aspirin (72.00% ± 4.17% vs. 69.73% ± 5.62%, respectively; P = NS). Significant differences were found between patients of group 2 treated with aspirin alone (69.73% ± 5.62%), after 2.0 days (60.14% ± 9.60%; P < 0.05), and after 4.8 ± 1.3 days (48.37% ± 11.19%; P < 0.05) with thienopyridine‐aspirin. Among 1,684 consecutive stented patients, 16 patients who presented an SAT (group 3) were compared with 30 other stented patients free of SAT (group 4). We found a significant difference between group 3 (63.28% ± 9.56%) and group 4 (39.80% ± 10.9%; P < 0.0001). VASP phosphorylation analysis may be useful for the detection of coronary SAT. Cathet Cardiovasc Intervent 2003;59:295–302.

Effect of Pravastatin on Angiographic Restenosis After Coronary Balloon Angioplasty

OBJECTIVES This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty. BACKGROUND Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. METHODS In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable, > 50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization). RESULTS At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence > 50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups. CONCLUSIONS Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.

Four-Year Follow-Up of TYPHOON (Trial to Assess the Use of the CYPHer Sirolimus-Eluting Coronary Stent in Acute Myocardial Infarction Treated With BallOON Angioplasty)

OBJECTIVES The aim of this study was to assess the long-term safety and efficacy of the CYPHER (Cordis, Johnson and Johnson, Bridgewater, New Jersey) sirolimus-eluting coronary stent (SES) in percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND Concern over the safety of drug-eluting stents implanted during PCI for STEMI remains, and long-term follow-up from randomized trials are necessary. TYPHOON (Trial to assess the use of the cYPHer sirolimus-eluting stent in acute myocardial infarction treated with ballOON angioplasty) randomized 712 patients with STEMI treated by primary PCI to receive either SES (n = 355) or bare-metal stents (BMS) (n = 357). The primary end point, target vessel failure at 1 year, was significantly lower in the SES group than in the BMS group (7.3% vs. 14.3%, p = 0.004) with no increase in adverse events. METHODS A 4-year follow-up was performed. Complete data were available in 501 patients (70%), and the survival status is known in 580 patients (81%). RESULTS Freedom from target lesion revascularization (TLR) at 4 years was significantly better in the SES group (92.4% vs. 85.1%; p = 0.002); there were no significant differences in freedom from cardiac death (97.6% and 95.9%; p = 0.37) or freedom from repeat myocardial infarction (94.8% and 95.6%; p = 0.85) between the SES and BMS groups. No difference in definite/probable stent thrombosis was noted at 4 years (SES: 4.4%, BMS: 4.8%, p = 0.83). In the 580 patients with known survival status at 4 years, the all-cause death rate was 5.8% in the SES and 7.0% in the BMS group (p = 0.61). CONCLUSIONS In the 70% of patients with complete follow-up at 4 years, SES demonstrated sustained efficacy to reduce TLR with no difference in death, repeat myocardial infarction or stent thrombosis. (The Study to Assess AMI Treated With Balloon Angioplasty [TYPHOON]; NCT00232830).

Sirolimus for below the knee lesions: Mid‐term results of SiroBTK study

Objectives: To assess the safety and efficacy of sirolimus‐eluting stents (SESs) in the treatment of severe intermittent claudication and critical limb ischaemia with “below‐the‐knee” lesions, unsuitable for surgery. Background: Limited published evidence suggests that drug‐eluting stents may offer significant improvements in the treatment of infrapopliteal lesions. Methods: Thirty consecutive patients with either severe intermittent claudication or critical limb ischemia (CLI), category 3–6 of Rutherford classification, and multivessel disease of infrapopliteal arteries (≥2 vessels) were treated with SES. Sixty‐two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of patients were male and 36% diabetic. The primary endpoint was clinical improvement and healing of ulcers at short term (1 month) and mid term (7.7 months). The secondary endpoint was primary vessel patency rate (angiographic or duplex assessment). All patients received clopidogrel (75 mg daily) or ticlopidine (150 mg daily) for 2 months or longer. Results: Angiographic and procedural success was achieved in all patients. At 7 months (7.7 ± 5.8), it was necessary to amputate 1 toe in one patient and 1 mid‐foot in another. Limb salvage was obtained in 100% of patients. Other events were: two cardiac deaths unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome, one contralateral CLI, and three recurrent homolateral claudication cases. All surviving patients had a mid‐term clinical improvement with 97% of primary patency (56 patent arteries on 58 arteries). Conclusion: Treatment of “below‐the‐knee” lesions with SES may provide an alternative treatment for patients with CLI.

Systematic primary aspiration in acute myocardial percutaneous intervention: a multicentre randomised controlled trial of the export aspiration catheter.

AIMS It is unclear whether primary aspiration can prevent distal embolisation and thereby improve myocardial perfusion in patients presenting with acute myocardial infarction (AMI) within 12 hours after onset. METHODS AND RESULTS At 24 centres in Europe and India, 249 AMI patients were randomised to primary aspiration with the Export aspiration catheter (Medtronic Vascular, Santa Rosa, CA, U.S.A.) followed by stenting (N=120) or to conventional stenting without primary aspiration (N=129). There were no significant differences between the 2 groups in baseline characteristics or target lesion TIMI scores. Procedure time was 36.7 +/- 18.0 minutes for primary aspiration followed by stenting versus 34.5 +/- 21.5 minutes for conventional stenting (P=0.08). Debris was obtained by primary aspiration from 85.3% of the arteries. The use of a bailout technique was significantly lower for primary aspiration than for conventional stenting (5.8% vs. 14.7%, P=0.02). For the primary endpoint of the combined rate of myocardial blush grade 3 and/or ST-segment resolution >50% to assess myocardial perfusion, primary aspiration followed by stenting was superior to conventional stenting (85.0% vs. 71.9%, P=0.025). Immediately postprocedure, the rate of myocardial blush grade 3 was 35.8% for primary aspiration followed by stenting versus 25.4% for conventional stenting (P=0.094). At 60 minutes post procedure, the rate of ST-segment resolution >50% was 73.5% for primary aspiration followed by stenting versus 64.8% for conventional stenting (P=0.218). Primary aspiration was also associated with a significantly higher postprocedure corrected TIMI frame count than conventional stenting (20 +/- 14.9 vs. 22.8 +/- 14, P=0.02). At 30 days, there were no differences between the treatments in the rate of major adverse cardiac and cerebral events. CONCLUSIONS Compared with conventional stenting, primary aspiration with the Export aspiration catheter followed by stenting improved myocardial reperfusion in AMI patients presenting with TIMI flow grade 0 to 1. Further study of primary aspiration involving larger numbers of patients is warranted to assess its effect on longer-term clinical outcome.

The French Randomized Optimal Stenting Trial: A Prospective Evaluation of Provisional Stenting Guided by Coronary Velocity Reserve and Quantitative Coronary Angiography

OBJECTIVES We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Randomised comparison of coronary stenting with and without balloon predilatation in selected patients

BACKGROUND The SWIBAP (stent without balloon predilatation) prospective randomised trial was designed to compare direct coronary stenting with stenting preceded by lesion predilatation with an angioplasty balloon. OBJECTIVE To determine the feasibility and safety of direct stenting in non-complex coronary lesions in a prospective study. PATIENTS AND DESIGN All patients < 76 years of age scheduled to undergo angioplasty of a non-complex, non-calcified lesion in a coronary artery of > 3.0 mm, who granted their informed consent, were randomised into the trial. In group I, the stent was placed without balloon predilatation, while in group II stent implantation was preceded by balloon predilatation. The primary end point was the angiographic result according to procedure assigned by randomisation. An intravascular ultrasound substudy was performed in 60 patients. RESULTS Stent implantation was successful without predilatation in 192 of the 197 group I patients (97.5%), and with predilatation in 197 of the 199 group II patients (99%) (NS). No in-hospital stent thrombosis or death occurred. Overall procedural times, fluoroscopy times, and volumes of contrast agent given (mean (SD)) in group I v group II were 23.50 (13.54) min v 27.96 (15.23) min (p = 0.002), 6.04 (4.13) min v 6.67 (3.65) min (NS), and 135 (65) ml v 157 (62) ml (p < 0.001), respectively. No major adverse cardiovascular events had occurred by 30 days. CONCLUSIONS The feasibility and safety of direct stenting of selected and non-complex coronary lesions is confirmed. This technique was as successful as the conventional approach and was associated with a minor reduction in fluoroscopic exposure and procedure time and the administration of less contrast agent.

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.

Assessment of the trackability, flexibility, and conformability of coronary stents: A comparative analysis

The efficacy and safety of coronary stent implantation depend on the mechanical features of these devices when deployed in atheromatous lesions of various morphologies. We evaluated the trackability, flexibility, and conformability of 17 coronary stents using specific mechanical bench tests. The quantifications used a dynamometer for assessment of trackability (maximal strength) and flexibility (stiffness) and a 3D optical gauging machine for assessment of conformability (distance between stent and arterial wall in a curvature). The maximal strength (measuring the trackability) ranged respectively from 0.24 ± 0.06 and 0.38 ± 0.03 N (Seaquest) to 1.31 ± 0.42 and 1.34 ± 0.35 N (Carbostent), concerning respectively curvatures of 90° (P < 0.0001) and 135° (P < 0.0001). The stiffness (measuring the flexibility) ranged from 0.53 ± 0.16 (Seaquest) to 1.28 ± 0.10 N/mm (NIR Royal; P < 0.0001). The mean distance between stent and external curvature (external conformability) ranged from 0.15 ± 0.06 mm (S7) to 0.57 ± 0.4 mm (NIR Royal; P < 0.0001). The mean distance between stent and internal curve (internal conformability) ranged from 0.26 ± 0.13 (S7) to 0.44 ± 0.12 mm (S670; P < 0.0001). These results may influence the choice of a particular stent adapted to a specific coronary anatomy. Cathet Cardiovasc Intervent 2003;59:496–503.

Intravascular Ultrasound–Guided Balloon Angioplasty Compared With Stent Immediate and 6-Month Results of the Multicenter, Randomized Balloon Equivalent to Stent Study (BEST)

Background—Balloon angioplasty guided by intravascular ultrasound (IVUS) makes it possible to choose the balloon size according to the true vessel diameter and to detect suboptimal results requiring subsequent stent implantation. The Balloon Equivalent to STent (BEST) study aimed to assess whether this strategy would give the same results as systematic stenting. Methods and Results—A total of 132 of 254 patients were randomized to IVUS-guided percutaneous transluminal coronary angioplasty (aggressive PTCA), and 122 were randomized to stenting (stent group). We hypothesized that a difference of <8% in the 6-month angiographic restenosis rate (primary end point) could be considered noninferior. The aggressive PTCA procedure was longer and had a greater use of contrast medium than stenting. In the aggressive PTCA group, crossover to stent was needed in 58 patients (44%). At 6 months, 20 of 119 patients (16.8±6.7%) in the aggressive PTCA group and 21 of 116 patients (18.1±7.0%) in the stent group had restenosis. The difference was −1.3%, with an upper limit of 95% confidence interval of 7.1% (ie, less than the noninferiority boundary). The in-stent restenosis rate was higher in the stent group (15.5% versus 5%;P =0.02). The differences in minimum lumen diameter, lumen cross-section area, and 1-year event rate were not significant. Conclusions—A strategy of IVUS-guided angioplasty with provisional stenting is feasible and safe. At the cost of a more complex procedure, it reduces the stent rate by half, with similar 6-month angiographic IVUS and clinical outcome compared with stent implantation.