John Cosgrave

Incidence and Predictors of Drug-Eluting Stent Thrombosis During and After Discontinuation of Thienopyridine Treatment

Background— The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents. Methods and Results— A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; P<0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; P=0.92). Conclusions— Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months.

Renal insufficiency following contrast media administration trial (REMEDIAL) : A randomized comparison of 3 preventive strategies

Background— Volume supplementation by saline infusion combined with N-acetylcysteine (NAC) represents an effective strategy to prevent contrast agent–induced nephrotoxicity (CIN). Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN. Methods and Results— Three hundred twenty-six consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n=111), sodium bicarbonate infusion plus NAC (n=108), and 0.9% saline plus ascorbic acid plus NAC (n=107). All enrolled patients had serum creatinine ≥2.0 mg/dL and/or estimated glomerular filtration rate <40 mL · min−1 · 1.73 m−2. Contrast nephropathy risk score was calculated in each patient. In all cases, iodixanol (an iso-osmolar, nonionic contrast agent) was administered. The primary end point was an increase of ≥25% in the creatinine concentration 48 hours after the procedure (CIN). The amount of contrast media administered (179±102, 169±92, and 169±94 mL, respectively; P=0.69) and risk scores (9.1±3.4, 9.5±3.6, and 9.3±3.6; P=0.21) were similar in the 3 groups. CIN occurred in 11 of 111 patients (9.9%) in the saline plus NAC group, in 2 of 108 (1.9%) in the bicarbonate plus NAC group (P=0.019 by Fisher exact test versus saline plus NAC group), and in 11 of 107 (10.3%) in the saline plus ascorbic acid plus NAC group (P=1.00 versus saline plus NAC group). Conclusions— The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.

Percutaneous Treatment With Drug-Eluting Stent Implantation Versus Bypass Surgery for Unprotected Left Main Stenosis A Single-Center Experience

Background— Improvements in results with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may extend their use in patients with left main coronary artery (LMCA) stenosis. Methods and Results— Two hundred forty-nine patients with LMCA stenosis were treated with PCI and DES implantation (n=107) or coronary artery bypass grafting (CABG) (n=142), in a single center, between March 2002 and July 2004. A propensity analysis was performed to adjust for baseline differences between the two cohorts. At 1 year, there was no statistical difference in the occurrence of death in PCI versus CABG both for the unadjusted (OR=0.291; 95% CI=0.054 to 1.085; P=0.0710) and adjusted analyses (OR=0.331; 95% CI=0.055 to 1.404; P=0.1673). PCI was correlated to a lower occurrence of the composite end points of death and myocardial infarction (unadjusted OR=0.235; 95% CI=0.048 to 0.580; P=0.0002; adjusted OR=0.260; 95% CI=0.078 to 0.597; P=0.0005) and death, myocardial infarction, and cerebrovascular events (unadjusted OR=0.300; 95% CI=0.102 to 0.617; P=0.0004; adjusted OR=0.385; 95% CI=0.180 to 0.819; P=0.01). No difference was detected in the occurrence of major adverse cardiac and cerebrovascular event at the unadjusted (OR=0.675; 95% CI=0.371 to 1.189; P=0.1891) and adjusted analyses (OR=0.568; 95% CI=0.229 to 1.344; P=0.2266). Conclusions— At 1 year, in this single-center, retrospective experience, there was no difference in the degree of protection against death, stroke, myocardial infarction, and revascularization between PCI with DES and CABG for LMCA disease.

Treatment of bifurcation lesions with two stents: one year angiographic and clinical follow up of crush versus T stenting

Objectives: To compare long term outcomes of the crush versus the T technique in bifurcation lesions. Design: 182 consecutive patients were identified who underwent percutaneous coronary interventions for bifurcation lesions with drug eluting stents between April 2002 and January 2004. Two techniques were used according to the operator’s discretion: crush (group C, n  =  121) or T (group T, n  =  61). Results: In-hospital outcome differed significantly between the two groups. Angiographic follow up was available for 142 (78%) patients. Groups C and T did not differ significantly regarding late loss (0.42 (0.39) mm v 0.34 (0.35) mm, p  =  0.52) and rate of restenosis (16.2% v 13.0%, p  =  0.80) in both the main and the side branch without final kissing balloon post-dilatation. However, when final kissing balloon post-dilatation was performed, group C had significantly lower late lumen loss (0.23 (0.21) mm v 0.37 (0.33) mm, p  =  0.02) and restenosis rate (8.6% v 26.5%, p  =  0.04) in the side branch. At one year’s clinical follow up, group C compared with group T had lower rates of target lesion revascularisation (14.0% v 31.1%, p  =  0.01) and target vessel revascularisation (16.5% v 32.8%, p  =  0.02). Conclusions: In non-selected bifurcation lesions treated with drug eluting stents, the restenosis rate remains relatively high in the side branch. Compared with the T stenting technique, crush stenting with kissing balloon post-dilatation is associated with a reduced rate of restenosis in the side branch.

Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention

BACKGROUND Drug-eluting stents reduce the risk of restenosis after percutaneous coronary intervention (PCI) but may pose a risk of thrombosis. Cilostazol, an oral antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia, could hold the promise of preventing both restenosis and thrombosis. We systematically reviewed randomized clinical trials (RCTs) on the angiographic and clinical impact of cilostazol after PCI. METHODS We searched RCT in BioMedCentral, CENTRAL, clinicaltrials.gov, EMBASE, and PubMed (November 2007). Coprimary end points were binary angiographic restenosis and repeat revascularization, abstracted and pooled by means of random-effect relative risks (RRs). Small study/publication bias was appraised with multiple methods. RESULTS A total of 23 RCTs were included (5428 patients), with median follow-up of 6 months. Pooled analysis showed that cilostazol was associated with statistically significant reductions in binary angiographic restenosis (RR = 0.60 [0.49-0.73], P < .001) and repeat revascularization (RR = 0.69 [0.55-0.86], P = .001). Cilostazol appeared also safe, with no significant increase in the risk of stent thrombosis (RR = 1.35 [0.71-2.57], P = .36) or bleeding (RR = 0.71 [0.43-1.16], P = .17). However, small study bias was evident for both binary restenosis (P < .001) and repeat revascularization (P < .001), suggesting that at least part of the apparent benefits of cilostazol could be due to this type of confounding effect. CONCLUSIONS Cilostazol appears effective and safe in reducing the risk of restenosis and repeat revascularization after PCI, but available evidence is limited by small study effects. Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients in which drug-eluting stents are contraindicated or when there is a need for neointimal hyperplasia inhibition.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Stent Implantation in Patients Taking Chronic Oral Anticoagulation

OBJECTIVES The purpose of this study was to evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation (AC) with warfarin is recommended. BACKGROUND The optimal antithrombotic strategy after percutaneous coronary intervention (PCI) for patients receiving AC is unclear. METHODS Consecutive patients who underwent stent implantation and were discharged on triple therapy (defined as the combination of aspirin and thienopyridines and AC) were analyzed. RESULTS Of the 127 patients with 224 lesions, 86.6% were men, with a mean age of 69.9 +/- 8.8 years. Drug-eluting stents (DES) were positioned in 71 (55.9%), and bare-metal stents (BMS) were positioned in 56 (44.1%) patients. Atrial fibrillation (AF) was the main indication (59.1%) for AC treatment. The mean triple therapy duration was 5.6 +/- 4.6 months, and clinical follow-up was 21.0 +/- 19.8 months. During the triple therapy period, 6 patients (4.7%) developed major bleeding complications; 67% occurred within the first month. No significant differences between DES and BMS were observed in the incidence of major (5.6% vs. 3.6%, respectively, p = 1.0) and minor (1.4% vs. 3.6%, respectively, p = 0.57) bleeding and mortality (5.6% vs. 1.8%, respectively, p = 0.39). A significant difference was observed in favor of DES in target vessel revascularization (14.1% vs. 26.8%, p = 0.041). CONCLUSIONS While receiving triple therapy, major bleeding occurred in 4.7% of patients; one-half of the events were lethal, and most occurred within the first month.

A novel approach to chronic total occlusions: the crosser system.

Objectives: To evaluate safety and efficacy of the CROSSER CTO Recanalization System (CROSSER). Background: The CROSSER, a novel device dedicated to recanalization of chronic total occlusions (CTO), relies on a monorail catheter delivering vibrational energy to facilitate the crossing of occluded coronary arteries. Methods: We included de novo or restenotic occlusions in native coronary arteries with typically unfavorable characteristics and a prior failed guidewire attempt either performed in a previous procedure or just before the usage of the CROSSER. The end points analyzed were technical success (ability to cross or facilitate a guidewire crossing into the true lumen), angiographic success (<20% residual stenosis and TIMI flow grade 3), and clinical success (angiographic success and freedom from major adverse cardiac events at 30 days). Results: Twenty‐eight patients (30 lesions) were included. The morphology was blunt in 83.3% and the length of the occlusion was >20 mm in 76.6%. The median age of the CTO was 9 months (range 3–60 months). Technical success was obtained in 19 (63%) occlusions and angiographic success in 16 (53%): 26.3% in lesions with prior procedural failure and 73.7% when CROSSER was attempted after initial guidewire failure. Complications were: one guidewire perforation without consequences and one peri‐procedural myocardial infarction (MI). No events occurred within 30‐day follow‐up after discharge. Conclusions: In our experience, the CROSSER System is safe and increases the success of opening CTO refractory to guidewires. This novel device may represent an useful adjunct to the armamentarium of the interventional cardiologist.

Drug-eluting stenting: the case for post-dilation.

In clinical practice, adequate stent deployment has an important effect on immediate and long-term results after percutaneous coronary interventions. In particular, suboptimal or incomplete stent expansion is associated with increased restenosis and target vessel revascularization rates and, especially with drug-eluting stents (DES), might also predispose to stent thrombosis. Notwithstanding the significant improvement in technique and materials in the last decade, adjunctive high-pressure balloon dilation is still necessary to improve the minimum stent area and the uniform volumetric stent expansion in a majority of the cases. Indeed, in the published reports, the incidence of incomplete stent deployment ranges from 20% to 30% of cases, but it is significantly higher in trials in which stent expansion was assessed by intravascular ultrasound. Although there are not enough randomized studies about this topic, data from published reports continue to support the use of proper post-dilation in the majority of patients undergoing both bare-metal stent and DES implantation. This review will summarize the different anatomical, clinical, and device-related variables for increased risk of suboptimal stent delivery, highlighting the importance of adequate high-pressure post-dilation to obtain optimal stent expansion to positively affect stent thrombosis and restenosis.

Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

BackgroundDual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition.MethodsWe studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E1; 2) VerifyNow-P2Y12 test, in which results are reported as absolute P2Y12-Reaction-Units (PRU) or % of inhibition (% inhibition).ResultsThirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E1 was 25.4% (IQR: 21.4–33.1%) and 3.5% (1.7–9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1st quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84–0.98, p < 0.0001) for % inhibition and 0.85 (0.72–0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.ConclusionIn conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y12 test may provide the best accuracy for the identification of patients with LR.

CTO recanalization by intraocclusion injection of contrast: The microchannel technique

Objectives: To assess the utilization of microinjection of contrast for the recanalization of chronic total occlusions (CTO). Background: Microchannels in CTOs have been considered important conduits for CTO crossing, utilizing dedicated guidewires. We postulated that microinjection of contrast immediately distal to the proximal cap of the CTO could identify and enlarge these microvessels, creating a passage for crossing the CTO with a floppy guidewire. Methods: A total of 32 patients with a CTO were treated with this technique. Following few millimetres penetration of the proximal fibrous cap of the occlusion with a dedicated CTO guidewire, the over‐the‐wire balloon was advanced into the proximal portion of the occlusion, and 50–100 μg of nitroglycerine followed by 1 ml of contrast was gently injected into the occluded segment. Technical success of the microchannel technique was defined as the ability to visualize the distal true lumen with microinjection of contrast and thereafter cross the CTO with a floppy guidewire in the absence of any dissection. Results: Overall, technical success of the microchannel technique was obtained in 20 (63%) with angiographic success in 19. In 12 (37%) cases there was a technical failure because of dissection, and we obtained recanalization of the artery in 7 of these 12 cases with another technique. There was only one case of periprocedural myocardial infarction in an unsuccessful procedure and no major adverse cardiac events or subacute stent thromboses were observed. Conclusions: Microinjection of contrast immediately distal to the proximal fibrous cap of a CTO may be an additional technique to facilitate recanalization of CTO.