Pramod K. Kuchulakanti

Correlates and Long-Term Outcomes of Angiographically Proven Stent Thrombosis With Sirolimus- and Paclitaxel-Eluting Stents

Background— Stent thrombosis (ST) is a serious complication of drug-eluting stent (DES) implantation regardless of the timing (acute, subacute, or late). The correlates of ST with DES are not yet completely elucidated. Methods and Results— From a total cohort of 2974 consecutive patients treated with DES since April 2003, we identified 38 patients who presented with angiographic evidence of ST (1.27%). The ST occurred acutely in 5 patients, subacutely (≤30 days) in 25 patients, and late (>30 days) in 8 patients. The clinical, angiographic, and procedural variables of these patients were compared with the remaining 2936 consecutive patients who underwent DES implantation and did not experience ST during a follow-up of 12 months. Logistic regression analysis was conducted to determine the correlates of ST. Compared with patients without ST, patients with ST had a higher frequency of diabetes, acute postprocedural renal failure, and chronic renal failure. There were more bifurcation lesions, type C lesions, and a trend for smaller-diameter stents. Discontinuation of clopidogrel was higher in these patients (36.8% versus 10.7%; P<0.0001). The mean duration to ST from the stent implantation was 8.9±8.5 days in subacute and 152.7±100.4 days in late thrombosis cases. Mortality was significantly higher in patients with ST compared with those without ST at 6 months (31% versus 3%; P<0.001). Multivariate analysis detected cessation of clopidogrel therapy, renal failure, bifurcation lesions, and in-stent restenosis as significant correlates of ST (P<0.05). Conclusions— ST continues to be a serious complication of contemporary DES use. Careful management is warranted in patients with renal failure and in those undergoing treatment for in-stent restenosis and bifurcations. Special focus on clopidogrel compliance may minimize the incidence of ST after DES implantation.

Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries

Objective: We aimed to determine the safety and efficacy of biobasorbable magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium stents carry the potential to overcome the limitations posed by permanent metallic stents such as chronic inflammation, late stent thrombosis, prolonged antiplatelet therapy, and artifacts when imaged by multislice‐computed tomography or magnetic resonance imaging. Methods: Magnesium alloy stents or stainless steel stents were randomly deployed in coronary arteries of domestic or minipigs. Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3 months. Results: At 3 days, magnesium alloy stents were intact, but started to show signs of degradation by 28 days. There was no evidence of stent particle embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days and 3 months, neointimal area was significantly less in magnesium alloy stent segments (2.44 ± 0.88 mm2 and 1.16 ± 0.19 mm2) as compared with the stainless steel stent segments (5.03 ± 1.5 mm2 and 1.72 ± 0.68 mm2, P < 0.001 and 0.02). Quantitative coronary analysis indicates that percentage area stenosis and percentage diameter stenosis in magnesium alloy stent segments improved significantly at 3 months as compared to 28 days. Despite decreased neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not improve significantly. Conclusion: Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.

Sirolimus-eluting stents and calcified coronary lesions: clinical outcomes of patients treated with and without rotational atherectomy.

This study examined the outcomes of patients who underwent sirolimus‐eluting stent (SES) implantation for the treatment of heavily calcified coronary lesions (HCCL) with and without the use of rotational atherectomy (rotablator). We investigated 150 consecutive patients with angiographic evidence of HCCL who underwent SES implantation. Sixty‐nine patients underwent SES implantation without the need of rotablator (SES), and 81 patients required rotational atherectomy to modify the plaque and facilitate the delivery of the stent (SES + rotational atherectomy). Clinical success was equivalent in both groups (>98%) and there were no in‐hospital outcome differences. At 6 months, the target lesion revascularization rate was 4.9% in SES vs. 4.2% in SES + rotational atherectomy groups, respectively (P = NS). Mortality at 6 months was 7.9% in the SES group vs. 6.8% in the SES + rotational atherectomy group (P = NS). SES performs well in patients with complex HCCL, with a relative low event rate. Lesions requiring rotational atherectomy to facilitate dilation and stenting had similar outcomes after SES implantation to those that could be stented without the need for rotablator.

Percutaneous coronary intervention with drug‐eluting stents in octogenarians: Characteristics, clinical presentation, and outcomes

Objectives: We aimed to compare clinical outcomes of octogenarians ≥80 years of age after coronary drug‐eluting stent (DES) implantation. Background: Although octogenarians constitute a fast‐growing portion of cardiovascular patients, they are not adequately represented in current clinical revascularization trials. Methods: We analyzed the data of 3,166 consecutive patients who underwent percutaneous coronary intervention (PCI) and DES implantation since March 2003. Periprocedural events, 1‐ and 6‐month clinical outcomes were compared between octogenarians (n = 339) and patients <80 years of age (n = 2,827). Results: Baseline characteristics revealed a higher prevalence of females (P < 0.001), Caucasians (P = 0.004), chronic renal failure (P < 0.001), heart failure (P < 0.001), number of diseased vessels (P = 0.009), and lower ejection fraction (P = 0.03) in octogenarians. Patients <80 years showed more positive family history (P < 0.001), hyperlipidemia (P = 0.006), smoking (P < 0.001), and obesity (P < 0.001). Clinical presentation and procedural success were similar in both groups as were death, myocardial infarction (MI), and repeat revascularization in‐hospital. At 6 months, restenosis rates were low and comparable. In the subgroup of octogenarians who presented with acute coronary syndrome, mortality (15% vs. 3%, P < 0.001) and Q‐wave MI occurred more often. Multivariate analysis revealed age >80 (P = 0.008), cardiogenic shock (P < 0.001), Q‐wave MI at presentation (P = 0.003), and length of hospital stay (P = 0.003) to be independent predictors of mortality. Conclusions: PCI with DES in octogenarians results in a similar reduction of restenosis rates when compared to patients <80 years. Yet in octogenarians who presented with acute coronary syndrome, incidence of mortality and Q‐wave MI at 6 months was higher as compared to younger patients.

Impact of sirolimus‐eluting stents on outcomes of patients treated for acute myocardial infarction by primary angioplasty

Sirolimus‐eluting stents (SESs) are currently being used in patients undergoing percutaneous coronary intervention (PCI). SESs have not been evaluated in the treatment of acute myocardial infarction by primary angioplasty. We report our initial experience with SESs implanted during primary angioplasty. One hundred and three patients were treated within 12 hr after onset of acute myocardial infarction (AMI) with primary angioplasty and SES implantation. Those patients were compared to 504 patients treated with bare metal stents (BMSs). Angiographic success (TIMI flow grade 3 and residual stenosis < 50%) was completed in 98% of patients with SESs and no subacute stent thrombosis was reported. In‐hospital outcomes were similar in the SES and BMS groups. At 6 months, major cardiac events were less frequent in the SES group than in the BMS group (9% vs. 24%, respectively; P < 0.001), driven by a lesser need for repeat revascularization with SESs (1% vs. 10.3% with BMSs; P = 0.014). Mortality at 6 months was 7% with SESs and 11% with BMSs (P = 0.14). SESs are safe and effective for the treatment of AMI by primary angioplasty. As compared to BMSs, SESs improve long‐term outcome after AMI, mainly by reducing the need for repeat revascularization.

Impact of overlapping drug-eluting stents in patients undergoing percutaneous coronary intervention

Background: Sirolimus‐eluting stent (SES) implantation for the treatment of single coronary lesions is proven to be effective and durable. However, the safety and efficacy of overlapping SES for the treatment of long lesions have not been well established. Objectives: We conducted a retrospective analysis to compare the clinical outcomes of overlapping versus nonoverlapping SES. Methods: Fifty‐five patients who received overlapping SES were compared with 39 patients who received nonoverlapping SES. Results: The baseline clinical and angiographic characteristics were balanced between the two study groups. The in‐hospital complications were similar between groups, except that non‐Q‐wave myocardial infarction was significantly higher in the Overlapping SES group when compared with the Nonoverlapping SES group (23.6% vs. 7.7%, P = 0.04). This higher rate of myonecrosis is due to periprocedural side branch compromises, including side branch narrowing, occlusion, and flow reduction. At 30 days and 6 months follow‐up, all clinical outcomes were similar between the study groups. In addition, the event‐free survival rate was similar between groups (P = 0.87). Conclusions: The implantation of overlapping SES for the treatment of long, native coronary lesions is feasible and effective but is associated with an increased rate of periprocedural myonecrosis. This phenomenon is caused primarily by side branch compromises, but does not have any adverse impact on late clinical events.

Therapeutic potential of oral antiproliferative agents in the prevention of coronary restenosis

The treatment of coronary artery disease has reached many milestones — from balloon angioplasty to drug-eluting stents. The last decade witnessed the revolution of bare metal stents with new designs, alloys and strut thicknesses. Yet restenosis, the aphorismic ‘Achilles heel’, remains to be conquered. The restenosis rates with balloon angioplasty alone are 30–40% and are reduced to 20–30% with stents. Although intravascular brachytherapy proved to be a durable and safely used technique to treat in-stent restenosis, clinical event rates were not reduced to single digits.Drug-eluting stents are showing positive results in this direction, but it is too early to predict their efficacy in various subsets of lesions. With the increased usage of these stents, there are reports of problems such as late stent malapposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. Furthermore, when multivessel stenting is considered, the cost of drug-eluting stents is a significant problem given the fact that these are no longer ‘zero restenosis’ devices.There is a definite need for a simple, safe and durable solution to restenosis. Oral agents are an alternative delivery strategy that can target multiple coronary lesions, which are targets for catheter-based revascularisation with any approved metal stent and with potentially lower cost. Although oral agents have been an interesting option to treat restenosis and several agents have been tested in trials since the 1980s, the results were disappointing.The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, and the focus on pathophysiological mechanisms, which centred mainly on platelets, growth factors and lipids, has changed to inflammation, endothelium and smooth muscle cell proliferation.Accordingly, the targets of pharmaceutical agents have shifted from platelets to cell cycle inhibition, smooth muscle cell proliferation and migration, synthesis of extra cellular matrix, and inflammatory mediators. Initial encouraging results with oral drugs such as cilostazol, sirolimus (rapamycin) and thiazolidinediones indicate a definite place for this strategy to reduce restenosis. A desirable oral agent would be anti-inflammatory, inhibit smooth muscle cell migration and proliferation, promote endothelial growth, and be well tolerated and free from significant adverse effects. It may be useful to start with a high loading dose before stent implantation and then follow with a short-term lower maintenance dose. Future trials should be aimed at finding an ideal agent, effective loading dose, maintenance dose and optimum duration of therapy.

Vascular complications following coronary intervention correlate with long-term cardiac events

We aimed to study the consequences and late outcomes of patients who experienced peripheral vascular complications (PVCs) following percutaneous coronary interventions (PCI). A retrospective analysis of the medical records of 10,669 patients who underwent PCI and experienced PVC between 1995 and 2002 was conducted. One thousand ninety‐six patients (10.27% of the study cohort) had PVC post‐PCI. After PCI, patients with PVC had higher rates of in‐hospital complications (P < 0.001) when compared to patients without PVC, including Q‐wave myocardial infarction (MI; 1.2% vs. 0.3%), coronary artery bypass grafting (CABG; 3.8% vs. 0.6%), and death (4.0% vs. 1.0%). At 1‐year follow‐up, late complications of MI (37.4% vs. 25.4%), non‐Q‐wave MI (34.9% vs. 22.7%), death (12.9% vs. 5.9%), and CABG (5.7% vs. 4.5%) were higher (< 0.001) in patients with PVC compared to those without. Multivariate analysis identified PVC as a significant predictor of 1‐year mortality (P = 0.045). This study underscores the need to make diligent efforts to minimize PVC and follow up these patients for future coronary events. Cardiovasc Interv 2004;62:181–185.

Bivalirudin‐associated intracoronary thrombosis during γ‐brachytherapy and its experimental validation in acute swine model

Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with β‐radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with γ‐radiation when bivalirudin is used. Catheter Cardiovasc Interv 2004;62:209–213.

Impact of three or more sirolimus-eluting stents versus paclitaxel-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention

The purpose of this study was to examine the clinical outcomes of patients who underwent stenting with ≥3 sirolimus‐eluting stents (SES) when compared with those treated with ≥3 paclitaxel‐eluting stents (PES).