Peter Ruygrok

Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II)

BACKGROUND The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. METHODS 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. FINDINGS Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US

Sirolimus in De Novo Heart Transplant Recipients Reduces Acute Rejection and Prevents Coronary Artery Disease at 2 Years A Randomized Clinical Trial

1020) per patient. INTERPRETATION Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Clinical and Angiographic Predictors of Restenosis After Stent Deployment in Diabetic Patients

Background—Sirolimus reduces acute rejection in renal transplant recipients and prevents vasculopathy in nonhuman primates and in-stent restenosis in humans. Its effects on rejection and transplant vasculopathy in human heart transplant recipients are unknown. Methods and Results—In a randomized, open-label study, sirolimus was compared with azathioprine in combination with cyclosporine and steroids administered from the time of cardiac transplantation. We report 6-month rejection rates (primary end point), 12-month safety and efficacy data, and 6- and 24-month graft vasculopathy data in 136 cardiac allograft recipients randomly assigned (2:1) to sirolimus (n=92) or azathioprine (n=44). At 6 months, the proportion of patients with grade 3a or greater acute rejection was 32.4% for sirolimus 3 mg/d (P=0.027), 32.8% for sirolimus 5 mg/d (P=0.013), and 56.8% for azathioprine. Patient survival at 12 months was comparable among groups. Intracoronary ultrasound at 6 weeks, 6 months, and 2 years demonstrated highly significant progression of transplant vasculopathy in azathioprine-treated patients. At 6 months, a highly significant absence of progression in intimal plus medial proliferation and significant protection against luminal encroachment was evident in sirolimus-treated patients, and these effects were sustained at 2 years. Conclusions—Sirolimus use from the time of transplantation approximately halved the number of patients experiencing acute rejection. The measurable development of transplant vasculopathy at 6 months and 2 years in patients receiving azathioprine was not observed in patients receiving sirolimus.

Drug-eluting stents for coronary bifurcations: Bench testing of provisional side-branch strategies

Background—Restenosis and consequent adverse cardiac events are increased in diabetics undergoing percutaneous coronary intervention. Use of intracoronary stents may ameliorate such risks; however, factors influencing the likelihood of restenosis after stent deployment in this high-risk patient subgroup are unknown. Methods and Results—We retrospectively analyzed all stented diabetic patients in 16 studies of percutaneous coronary intervention, all of which underwent core angiographic analysis at Cardialysis, Rotterdam. Univariate and multivariate analyses, with 37 clinical and angiographic variables, compared those with and without restenosis and predicted restenosis rates calculated through the use of reference charts derived from angiographic data. Within the studies, 418 of 3090 (14%) stented patients with 6-month angiographic follow-up had diabetes. Restenosis (≥50% diameter stenosis at follow-up) occurred in 550 of 2672 (20.6%) nondiabetic and 130 of 418 (31.1%) diabetic patients (P <0.001). Univariate predictors of restenosis in diabetics were smaller vessel reference diameter (RD) (P <0.001), smaller minimal luminal diameter before stenting (P =0.01), smaller minimal luminal diameter and percent diameter stenosis after stenting (P <0.001, P =0.04), greater stented length of vessel (P <0.001), and reduced body mass index (BMI) (P =0.04). With the use of multivariate analysis, only smaller RD (P =0.003), greater stented length of vessel (P =0.04), and reduced BMI (P =0.04) were associated with restenosis. Reference charts demonstrated an incremental risk of restenosis that appears solely dependent on vessel RD. Conclusions—Restenosis after stent deployment is significantly increased in diabetic patients. Vessel caliber, stented length of vessel, and lower BMI are predictors of in-stent restenosis in patients with diabetes. Furthermore, vessel caliber affected the predicted risk of restenosis incrementally.

Does angiography six months after coronary intervention influence management and outcome

The objective of this study was to bench‐test provisional bifurcation stenting strategies to provide insights on how best to perform these with drug‐eluting stents (DESs). Bifurcation stenting with DESs reduces restenosis compared with bare metal stents (BMSs). Outcomes with a single DES are better than with two DESs but if the main branch is stented, there needs to be a reliable strategy for provisionally stenting the side‐branch with full ostial scaffolding and drug application. Stents were photographed in a phantom after deployment with different strategies. With provisional T‐stenting, placement of the side‐branch stent without gaps is difficult. The internal (or reverse) crush strategy fully scaffolds the side‐branch ostium but is experimental. The culotte technique providing excellent side‐branch ostial coverage is easier to perform with open‐cell or large‐cell stent design. In general, kissing balloon postdilatation improves stent expansion, especially at the ostium, and corrects distortion. However, a main‐branch kissing balloon of smaller diameter than the deploying balloon causes distortion. Final main‐branch postdilatation or sequential postdilatation prevents distortion after the internal crush strategy.

The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response: An Analysis From the PRINC (Plavix Response in Coronary Intervention) Trial

OBJECTIVES This study was performed to assess whether angiography six months after coronary balloon angioplasty or stent implantation has an influence on clinical management and one-year outcome. BACKGROUND The Benestent II study randomized 827 patients to balloon angioplasty or stent implantation. A subrandomization was undertaken allocating patients to six-month clinical follow-up (CF) or clinical and angiographic follow-up (AF). METHODS Seven hundred and six patients (349 CF and 357 AF) had no intercurrent angiography, so that restenosis and disease progression elsewhere remained unknown until the time of six-month follow-up. These two groups, which were well matched at enrolment, were compared with respect to symptoms, medication and major cardiac events defined as death, myocardial infarction and need for revascularization at six and 12 months. RESULTS At six-month follow-up, 53 (15%) of the CF and 76 (21%) of the AF patients had stable angina (p = 0.041), while 5 (1%) and 4 (1%) had symptoms of unstable angina. At 12-month follow-up, 44 (13%) patients in both groups had stable angina, and only 1 patient in the CF group had unstable angina. Seventy-seven patients (27 CF and 50 AF; p < 0.01) had major cardiac events between 6 and 12 months. Of the 349 patients in the CF group, 21 underwent repeat percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery between 6 and 12 months, compared with 44 of the 357 patients in the AF group (relative risk 2.05 [1.24 to 3.37], p = 0.003). CONCLUSIONS Patients who had AF six months after balloon angioplasty or stent implantation experienced more repeat revascularization procedures than those who had CF. They also had significantly more angina at six-month follow-up but this may be due to bias.

Long-term clinical outcome after stent implantation in saphenous vein grafts

OBJECTIVES This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. BACKGROUND Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). METHODS Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. RESULTS CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). CONCLUSIONS Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).

A Prospective, Multicenter Trial of the VentrAssist Left Ventricular Assist Device for Bridge to Transplant : Safety and Efficacy

OBJECTIVES We sought to determine the role of stent implantation in vein grafts by evaluating the long-term clinical outcome and estimated event-free survival at 5 years in 62 patients and by comparing our data with those of other treatment modalities previously reported. BACKGROUND Patients with recurrent angina after coronary artery bypass graft surgery pose a problem. Stent implantation has been advocated in an effort to avoid repeat operation and to address the limitations of balloon angioplasty. METHODS Patients undergoing stenting of a vein graft were entered into a dedicated data base. They were screened for death, infarction, bypass surgery and repeat angioplasty. Procedure-related events were included in the follow-up analysis. Survival and event-free survival curves were constructed by the Kaplan Meier method. RESULTS A total of 93 stents (84 Wallstent and 9 Palmaz-Shatz) were implanted in 62 patients. During the in-hospital period seven patients (11%) sustained a major cardiac event: two deaths (3%), two myocardial infarctions (3%) and three urgent bypass surgeries (5%). The clinical success rate, therefore, was 89%. During the follow-up period (median 2.5 years, range 0 to 5.9), another five patients (8%) died, 14 (23%) sustained a myocardial infarction, 12 (20%) underwent bypass surgery, and 14 (23%) underwent angioplasty. The estimated 5-year survival and event-free survival rates (free from infarction, repeat surgery and repeat angioplasty) were (mean +/- SD) 83 +/- 5% (95% confidence interval [CI] 73% to 93%) and 30 +/- 7% (95% CI 16% to 44%), respectively. CONCLUSIONS The in-hospital outcome of patients who underwent stent implantation in a vein graft is acceptable, but the long-term clinical outcome is poor. It is unlikely that mechanical intervention alone will provide a satisfactory or definite answer for the patient with graft sclerosis over the long term.

Stent longitudinal flexibility : A comparison of 13 stent designs before and after balloon expansion

BACKGROUND The increasing prevalence of chronic heart failure has stimulated the ongoing development of left ventricular assist devices (LVADs) for both bridge-to-transplant (BTT) and destination therapy (DT). The aim of this prospective, multicenter clinical trial was to determine the efficacy and safety of a third-generation LVAD, the VentrAssist, in a BTT cohort. METHODS Patients (n = 33) with end-stage chronic heart failure who required circulatory support as BTT therapy were implanted with a VentrAssist device. The primary outcome was survival until transplant or transplant eligibility with the device in situ at trial end-point (Day 154 after implant). The secondary outcomes were pump flow index and end-organ function. Safety, patient functional status and resource use were also assessed. RESULTS At trial end-point, the success rate was 82% (39.4% transplanted, 42.4% transplant-eligible). The LVAD pump flow index (median >or=2.7 liters/min/m(2)) was sufficient to maintain an adequate circulation and significantly improve end-organ function. Of the 77 protocol-defined serious adverse events, most occurred within 30 days of implantation. No patients died as a direct result of pump failure or malfunction. After implantation, patient functional status improved, with 70% of patients achieving hospital discharge, and resource use was reduced. CONCLUSIONS This trial demonstrated a favorable efficacy and safety profile for use of the VentrAssist LVAD in BTT patients.

Relationships between vascular calcification, calcium metabolism, bone density, and fractures†

Longitudinal flexibility is an important property of coronary stents, facilitating delivery and allowing the expanded stent to conform to vessel contour. Subjective descriptions of flexibility abound, but there are few independent quantitative data to aid stent selection. A three‐point bend test was employed to measure stiffness, the reciprocal of flexibility, for 13 stent designs in the unexpanded (bare) state, then after expansion with a 3.5‐mm balloon. For eight of the designs, stiffness of the proprietary stent/balloon delivery system was also measured. In the unexpanded state, there was a wide spread of stiffness, which ranged from 0.5 ± 0.2 to 91.5 ± 10.0 g force/mm, depending on design. Stiffness was least for the coil (Wiktor and Crossflex) and hybrid (AVE GFX and Bard XT) designs. The MultiLink was the most flexible and the Crown the stiffest of the slotted tube designs. All stents became stiffer upon expansion. For most manufacturer‐mounted stents, the delivery balloon was the main determinant of stent/balloon delivery system stiffness. Manufacturer‐mounted stent profile ranged from 1.15 ± 0.11 mm for the Jostent to 1.53 ± 0.05 mm for the MultiLink system. Independent quantitative assessment of characteristics such as flexibility and profile should aid rational comparison of stent designs. Cathet. Cardiovasc. Intervent. 50:120–124, 2000.