A universal drug delivery catheter for the treatment of infrapopliteal arterial disease using liquid therapy.

OBJECTIVE: The objective of this study was to investigate the safety and feasibility of treating infrapopliteal lesions using a novel drug delivery catheter locally delivering liquid paclitaxel. BACKGROUND: Balloon angioplasty is currently the Gold Standard to treat below-the-knee disease; however, restenosis continues to be a great challenge following these percutaneous revascularization procedures. METHODS: The Occlusion Perfusion Catheter for Optimal Delivery of Paclitaxel for the Prevention of Endovascular Restenosis (COPPER-A) study-Below-the-Knee Cohort was a prospective, nonrandomized, multicenter, feasibility, and safety study that enrolled 35 patients at 11 participating sites. The safety endpoints at 1, 3, and 6 months were freedom from thrombosis, major amputation in the target limb and target limb related death. The efficacy endpoints were primary patency and freedom from clinically driven target lesion revascularization at 6 months. RESULTS: All patients tolerated the procedure well with no reports of adverse procedural events. Thirty-five patients were treated with a mean lesion length of 112 ± 81.2 mm with the lesion length range of 20-286 mm. At 6-month follow-up, primary patency was 89.3% and freedom from clinically driven target lesion revascularization was 96.4%. No patients demonstrated thrombosis, major amputation in the target limb and target limb related death at the 1-, 3- and 6-months follow-up intervals. CONCLUSIONS: The results of this multi-center study demonstrated that infrapopliteal arteries can be safely and effectively treated with liquid paclitaxel using the occlusion perfusion catheter.

Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.

OBJECTIVES: The aim of the study is to evaluate the safety and effectiveness of treating femoropopliteal in-stent restenosis (ISR) with debulking with excimer laser followed by implantation of a VIABAHN endoprosthesis. BACKGROUND: The optimal treatment strategy for femoropopliteal ISR is unclear. METHODS: The SALVAGE study is a multicenter prospective registry involving nine US centers. Patients with femoropopliteal ISR with moderate to severe intermittent claudication or critical limb ischemia (Rutherford categories 2-5) and an ankle-brachial index (ABI) =0.8 were treated with excimer laser and the VIABAHN endoprosthesis. The primary efficacy endpoint is primary patency at 12 months as measured by duplex ultrasonography. The primary safety endpoint is the major adverse event (MAE) rate at 30 days. RESULTS: Twenty-seven patients were enrolled. The mean lesion length was 20.7 ± 10.3 cm. The majority of lesions were TASC (TASC I) C and D (81.4%). All lesions were pretreated with excimer laser and percutaneous transluminal angioplasty (PTA) prior to VIABAHN implantation. Technical success was achieved in 100% of cases. There were no MAE at 30 days. Primary patency at 12 months was 48%. The ankle brachial index increased from 0.58 ± 0.24 at baseline to 0.90 ± 0.17 at 12 months. There was improvement in all quality-of-life parameters. The 12-month TLR rate was 17.4%. CONCLUSIONS: The strategy of excimer laser atherectomy and PTA followed by implantation of a self-expanding stent graft for the treatment of femoropopliteal ISR is safe and associated with high procedural success. Primary patency rate at 12-months was suboptimal; however, the TLR rate was low.

Percutaneous lower-extremity arterial interventions with primary balloon angioplasty versus Silverhawk atherectomy and adjunctive balloon angioplasty: randomized trial.

PURPOSE: Target lesion revascularization (TLR) with primary percutaneous transluminal angioplasty (PTA) versus SilverHawk atherectomy and adjunctive PTA of de novo infrainguinal disease has not been well defined. This study was conducted to compare the two approaches. MATERIALS AND METHODS: In this prospective, two-center randomized trial of PTA versus atherectomy of infrainguinal vessels, the primary endpoint of TLR was evaluated at 1 year. Secondary endpoints included the rate of "bailout" stent placement for suboptimal acute angiographic results and the rate of target vessel revascularization (TVR). RESULTS: Fifty-eight patients were included in the study. Of these, 29 (36 vessels) were randomized to the atherectomy arm and 29 (48 vessels) to the PTA arm. Final acute angiographic success rates were 100% in the PTA arm and 97.2% in the atherectomy arm (P value not significant). There was no statistical difference in TLR (16.7% vs 11.1%) or TVR (21.4% vs 11.1%) between the PTA and atherectomy groups, respectively. Bailout stent placement was performed in 18 of 29 patients (62.1%) in the PTA arm and eight of 29 patients (27.6%) in the atherectomy arm (P = .017). Major adverse events were similar between the PTA and atherectomy arms. Finally, when embolic filter protection was used, distal macroembolization occurred in 11 of 17 patients (64.7%) treated with atherectomy versus none of 10 in the PTA group (P < .001). CONCLUSIONS: TLR and TVR at 1 year were statistically similar in atherectomy and primary PTA. Atherectomy reduced the need for bailout stent placement compared with primary PTA.

Carotid artery stenting in high surgical risk patients using the FiberNet embolic protection system: the EPIC trial results.

OBJECTIVE: The multicenter EPIC (FiberNet Embolic Protection System in Carotid Artery Stenting Trial) single-arm trial evaluated the 30-day outcomes of a new design concept for embolic protection during carotid artery stenting (CAS). BACKGROUND: Embolic protection filters available for use during CAS include fixed and over-the-wire systems that rely on embolic material capture within a "basket" structure. The FiberNet Embolic Protection System (EPS), which features a very low crossing profile, consists of a three-dimensional fiber-based filter distally mounted on a 0.014 inch guidewire with integrated aspiration during filter retrieval. METHODS: The trial enrolled 237 patients from 26 centers. Demographics, clinical and lesion characteristics, as well as adverse events through a 30-day follow-up were recorded. The mean age of the patients was 74 years, 64% were male and 20% had symptomatic carotid artery disease. RESULTS: The combined major adverse event (MAE) rate at 30 days for all death, stroke, and myocardial infarction was 3.0%. There were three major strokes (two ischemic and one hemorrhagic) and two minor strokes (both ischemic) for a 2.1% 30-day stroke rate. The procedural technical success rate was 97.5% and macroscopic evidence of debris was reported in 90.9% of the procedures. CONCLUSIONS: The FiberNet EPS, used with commercially available stents, produced low stroke rates following CAS in high surgical risk patients presenting with carotid artery disease. The unique filter design including aspiration during retrieval may have contributed to the low 30-day stroke rate reported during CAS in patients considered at high risk for complications following carotid endarterectomy (CEA).

In-hospital safety and effectiveness of bivalirudin in percutaneous peripheral interventions: data from a real-world registry.

PURPOSE: To present real-world data to evaluate the safety and effectiveness of bivalirudin, a direct thrombin inhibitor, in an unselected group of patients undergoing percutaneous peripheral interventions (PPI). METHODS: Data were extracted from a prospectively collected peripheral vascular registry developed for quality assurance measures at 2 centers. Of 398 consecutive patients (195 men; mean age 69.4+/-11.3 years) who underwent PPI in a 2-year period, 369 (92.7%) received bivalirudin (0.75 mg/kg bolus followed by a 1.75 mg/kg/h infusion) and 29 (7.3%) received unfractionated heparin (UFH). In the bivalirudin sample, critical limb ischemia was present in 28.0% of patients, TASC D lesion in 29.5%, and angiographic thrombus in 7.8% of vessels. Demographic, clinical, procedural, and angiographic variables and in-hospital complications were analyzed. All in-hospital adverse events were independently adjudicated. RESULTS: Procedural success (<30% residual narrowing) was achieved in 359 (97.3%) patients receiving bivalirudin. Adverse events included stroke (1, 0.3%), acute renal failure (1, 0.3%), major bleeding (3, 0.8%), distal embolization (11, 3.0%), vascular access complications (2, 0.5%), and minor amputation (2, 0.5%). CONCLUSION: Bivalirudin had an excellent safety profile in a real-life cohort of patients undergoing PPI, including high-risk patients with critical limb ischemia and TASC D lesions. In-hospital major bleeding and other adverse events were infrequent. A randomized trial of bivalirudin versus UFH is needed to verify these results and establish bivalirudin as a standard anticoagulant in PPI.

Embolic protection and platelet inhibition during renal artery stenting.

BACKGROUND: Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown. METHODS AND RESULTS: One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2x2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease-derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined (P<0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2x2 design (P<0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0+/-27% versus -10+/-20%; P<0.05), embolic protection was not (-1+/-28% versus -10+/-20%; P=0.08). An interaction was observed between abciximab and embolic protection (P<0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (P<0.01). CONCLUSIONS: Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone.

Excimer laser recanalization of femoropopliteal lesions and 1-year patency: results of the CELLO registry.

PURPOSE: To evaluate the safety and efficacy of a modified laser catheter designed for the endovascular treatment of peripheral artery disease (PAD) affecting the superficial femoral artery (SFA) and proximal popliteal artery. METHODS: The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) study was a single-arm, prospective registry conducted at 17 investigational sites in the United States. The primary endpoint was the reduction in index lesion percent diameter stenosis (% DS) measured by Doppler ultrasound following laser ablation prior to any adjunctive therapy. The primary safety endpoint was major adverse events at 6 months. Sixty-five patients (39 men; mean age 68.3+/-10.1 years) with intermittent claudication, stenotic lesions >70% by visual assessment, a reference vessel diameter >or=4.0 and or=1.0 and

Clinical Conference Proceedings: 15th Biennial International Andreas Gruentzig Society Meeting.

The International Andreas Gruentzig Society is an educational society of physicians and scientists interested in cardiovascular and related fields. Members cooperate in the advancement of knowledge and education through research, publication, study, and teaching in the fields of cardiovascular disease. This summary reflects the proceedings from the recent scientific meeting to assess current clinical problems and propose future directions and possible solutions.

Dethrombosis of the lower extremity arteries using the power-pulse spray technique in patients with recent onset thrombotic occlusions: results of the DETHROMBOSIS Registry.

PURPOSE: To assess the presence of thrombus using intravascular ultrasound (IVUS) and evaluate the feasibility of combined thrombolysis [power-pulse spray (P-PS)] and rheolytic thrombectomy (RT) in patients with recent-onset limb ischemia (<6 months) due to total occlusion of at least 1 infrainguinal vessel. METHODS: Seventeen patients (12 women; mean age 68.3+/-10.7 years) enrolled in a prospective registry underwent IVUS imaging at baseline, after treatment with P-PS using tissue plasminogen activator and RT (AngioJet), and prior to definitive treatment of the vessel. The primary safety endpoints were major bleeding, distal embolization, vascular access complications, and renal failure. Effectiveness outcomes were (1) procedural success with a residual stenosis <30%, (2) IVUS-documented resolution of the thrombus, and (3) the combined clinical endpoint of procedure-related death, stroke, unplanned amputation, and unplanned urgent revascularization of the treated limb. RESULTS: At baseline, the majority of patients (16, 94.1%) had a definite thrombus identified by IVUS; in the remaining patient (6.3%), thrombus was likely to be present according to the IVUS scan. By angiography, 2 (11.8%) patients had a definite grade 3 thrombus and 5 (29.4%) patients had a grade 1 thrombus (modified TIMI scale) at baseline. IVUS data were available pre and post P-PS/RT in 16 (94.1%) patients. In 10 (62.5%), the thrombus was partially resolved; in 5 (31.25%), there was no apparent change. The thrombus appeared to have completely resolved in only 1 (6.3%) patient. Embolization occurred in 3 (17.6%) patients with no adverse clinical sequelae. The combined clinical endpoint was met in 1 (5.9%) of 17 patients. After final definitive treatment of the vessel, acute procedural success was 100%, with no angiographic filling defects seen. CONCLUSION: Thrombus is present in most if not all patients with a recent history of limb ischemia who are found to have an occluded culprit vessel. The application of the P-PS/RT led to partial or complete thrombus resolution in about two thirds of the patients treated. The overall safety outcome was favorable, but large studies are needed to test the effectiveness of the P-PS/RT technique prior to routine use.

Elevated levels of homocysteine predict cardiovascular death, nonfatal myocardial infarction, and symptomatic bypass graft disease at 2-year follow-up following coronary artery bypass surgery.

Severe graft disease occurs in patients at a rate of approximately 15% within the first year of coronary artery bypass grafting (CABG). In this study, the authors examined predictors of the combined end point of death, nonfatal myocardial infarction (MI), and bypass graft disease at 2-year follow-up after CABG. One hundred twenty-one consecutive patients were included in this study after informed consent was obtained. In univariate analysis, there was a significantly (P<.05) higher homocysteine level (11.0 ng/mol vs 9.7 ng/mol, P=.04) in patients who met the combined end point vs those who did not. There were no statistically significant differences in the following: low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and lipoprotein(a) values; age; body mass index; smoking and diabetes status; statin or aspirin use; creatinine level; hematologic markers; left ventricular ejection fraction; number of bypass grafts; and distribution of coronary artery disease. Logistic regression analysis modeling for low-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, and homocysteine showed that homocysteine value (P=.016) was an independent predictor of the primary combined end point.

Gender differences in adhering to national guidelines in a community lipid clinic.

The aggressive treatment of hypercholesterolemia improves morbidity and mortality in patients with a history of cardiovascular disease irrespective of gender. Electronically tracked data on 4324 patients enrolled in a community lipid clinic were analyzed for gender differences in lipid values and adherence to national guidelines in lipid management. Women were older, more likely to be diabetic and/or hypertensive, and have a family history of coronary heart disease. Women also had higher initial total cholesterol, low-density lipoprotein, and triglyceride levels and were more likely to be at goal at entry for high-density lipoprotein. Men were more likely to have coronary heart disease and lower high-density lipoprotein and were more likely to be at goal at entry for triglyceride level. There were no gender differences in low-density lipoprotein at goal at entry or rate of current smoking. All lipid parameters appeared better with age, irrespective of gender. More men than women reached goal for their low-density lipoprotein (61.5% vs 51.7%) and triglyceride (36.9% vs 25.1%) levels, whereas more women than men reached goal for their high-density lipoprotein (33.1% vs 22.2%). The authors conclude that there are significant gender differences in lipid values at entry to a community lipid clinic and in achieving National Cholesterol Education Program targets following the initiation of therapy. A possible gender-independent survivorship effect exists for low-density lipoprotein and high-density lipoprotein.

A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study.

OBJECTIVES: The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND: In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS: We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS: The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS: Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.

Routine visualization of the left internal mammary artery before bypass surgery: is it necessary?

The left internal mammary (LIMA) is an ideal conduit for bypassing the left anterior descending artery (LAD) during coronary artery bypass surgery (CABG). In this study, we evaluate the frequency of significant disease in the LIMA prior to CABG and describe associated significant lateral costal branches (> 1.5 mm), subclavian disease and vertebral disease. In 115 consecutive patients referred to CABG, 101 patients met the inclusion criteria. All patients who underwent routine visualization of the LIMA vessels were reviewed and quantitatively analyzed by an independent reader. Disease in the LIMA, left subclavian and vertebral arteries were graded and considered significant if lesions were > 50%. Lateral costal branches of the LIMA were also noted for their presence and size. Of the 101 patients, 87.1% of the LIMAs prior to surgery were without any disease. One LIMA had a 25-50% narrowing and the remaining LIMAs showed 0-25% disease. Of the LIMAs, 48.5% had lateral costal branches with diameters > 1.5 mm. The incidence of significant left vertebral disease and proximal subclavian disease was 37.6% and 5%, respectively. Cardiolite stress imaging post-CABG (n = 75) showed that when ischemia persisted in the anterior wall in patients with a LIMA to the LAD, this was not associated with the presence of significant LIMA disease, lateral costal branches, or subclavian disease identified pre-operatively. We conclude that the LIMA rarely shows significant disease on routine visualization prior to CABG. Asymptomatic subclavian artery disease and the presence of lateral costal branches pre-operatively did not correlate with post-CABG ischemia in the LAD territory.

Multidisciplinary approach to the diagnosis and management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is frequently diagnosed after permanent damage has occurred, resulting in a high rate of morbidity, amputation, and loss of life. Early and ongoing diagnosis and treatment is required for this progressive disease. Lifestyle modifications can prevent or delay disease progression and improve symptoms. Limb-sparing endovascular interventions can restore circulation based on appropriate diagnostic testing to pinpoint vascular targets, and intervention must occur as early as possible to ensure optimal clinical outcomes. An algorithm for the diagnosis and management of PAD was developed to enable a collaborative approach between the family practice and primary care physician or internist and various specialists that may include a diabetologist, endocrinologist, smoking cessation expert, hypertension and lipid specialist, endovascular interventionalist, vascular surgeon, orthopedist, neurologist, nurse practitioner, podiatrist, wound healing expert, and/or others. A multidisciplinary team working together has the greatest chance of providing optimal care for the patient with PAD and ensuring ongoing surveillance of the patient's overall health, ultimately resulting in better quality of life and increased longevity for patients with PAD.

Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis).

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of excimer laser atherectomy (ELA) with adjunctive percutaneous transluminal angioplasty (PTA) versus PTA alone for treating patients with chronic peripheral artery disease with femoropopliteal bare nitinol in-stent restenosis (ISR). BACKGROUND: Femoropopliteal stenting has shown superiority to PTA for lifestyle-limiting claudication and critical limb ischemia, although treating post-stenting artery reobstruction, or ISR, remains challenging. METHODS: The multicenter, prospective, randomized, controlled EXCITE ISR (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis) trial was conducted across 40 U.S. centers. Patients with Rutherford Class 1 to 4 and lesions of target lesion length ≥4 cm, vessel diameter 5 to 7 mm were enrolled and randomly divided into ELA + PTA and PTA groups by a 2:1 ratio. The primary efficacy endpoint was target lesion revascularization (TLR) at 6-month follow up. The primary safety endpoint was major adverse event (death, amputation, or TLR) at 30 days post-procedure. RESULTS: Study enrollment was stopped at 250 patients due to early efficacy demonstrated at a prospectively-specified interim analysis. A total of 169 ELA + PTA subjects (62.7% male; mean age 68.5 ± 9.8 years) and 81 PTA patients (61.7% male; mean age 67.8 ± 10.3 years) were enrolled. Mean lesion length was 19.6 ± 12.0 cm versus 19.3 ± 11.9 cm, and 30.5% versus 36.8% of patients exhibited total occlusion. ELA + PTA subjects demonstrated superior procedural success (93.5% vs. 82.7%; p = 0.01) with significantly fewer procedural complications. ELA + PTA and PTA subject 6-month freedom from TLR was 73.5% versus 51.8% (p < 0.005), and 30-day major adverse event rates were 5.8% versus 20.5% (p < 0.001), respectively. ELA + PTA was associated with a 52% reduction in TLR (hazard ratio: 0.48; 95% confidence interval: 0.31 to 0.74). CONCLUSIONS: The EXCITE ISR trial is the first large, prospective, randomized study to demonstrate superiority of ELA + PTA versus PTA alone for treating femoropopliteal ISR. (Randomized Study of Laser and Balloon Angioplasty Versus Balloon Angioplasty to Treat Peripheral In-stent Restenosis [EXCITE ISR]; NCT01330628).

Usefulness of optical coherent reflectometry with guided radiofrequency energy to treat chronic total occlusions in peripheral arteries (the GRIP trial).

Optical coherent reflectometry, a forward-looking, fiberoptic-guided device was used in 72 patients to direct radiofrequency energy across the central intraluminal portion of 75 chronic total occlusions in peripheral arteries (iliac, femoral, and popliteal) that failed attempts with conventional guidewires. The system was successful in crossing 76% of the chronic total occlusions with no clinical perforations or distal embolizations, and complications consisted of a single dissection greater than or equal to grade C.

Practical issues of platelet glycoprotein IIb/IIIa receptor inhibition: saving lives and saving money.

Abciximab is a monoclonal, human chimeric antibody with unique pharmacodynamics, pharmacokinetics, and receptor-specificity that distinguishes it from the small-molecule platelet glycoprotein IIb/IIIa receptor inhibitors. Abciximab has consistent, well-defined dosing and robust clinical results. Pooled data across abciximab trials comprising 9290 patients at maximum duration of follow-up demonstrates a 19% reduction in the relative risk of mortality (P =.003). There is a misperception of the cost of abciximab that focuses solely on the acquisition price of the drug. Cost-effectiveness analysis models compare the incremental improvement in clinical outcomes related to the increase in cost. Abciximab is extremely cost-effective in cost per life-year saved and is very attractive economically compared to alternative spending of health care dollars.

Effectiveness of statin-gemfibrozil combination therapy in patients with mixed hyperlipidemia: experience of a community lipid clinic and safety review from the literature.

This retrospective study was carried out to assess the effectiveness of statin-gemfibrozil combination therapy in a community practice lipid clinic and to review safety data from published literature. Forty-six consecutive patients received a statin and gemfibrozil combination for resistant hyperlipidemia to either agent therapy. Fasting total cholesterol (mg/dL), high-density lipoprotein cholesterol (mg/dL), and triglycerides (mg/dL) were measured. Low-density lipoprotein cholesterol (mg/dL) was calculated using the Friedewald formula if triglycerides were <400 mg/dL. Combination therapy reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides by 11% (p=0.02), 22% (p=0.049), and 39% (p=0.0002), respectively, and raised high-density lipoprotein cholesterol by 5% (p=0.3). A pooled analysis of 838 patients from the literature on statin-gemfibrozil combination therapy revealed an incidence of myositis and severe myopathy of 0.7% and 0.6%, respectively (excluding cerivastatin). We conclude that statin-gemfibrozil combination therapy is effective in significantly reducing total cholesterol, low-density lipoprotein cholesterol, and triglycerides with a trend toward raising high-density lipoprotein cholesterol in patients with hyperlipidemia resistant to either agent alone. Myositis and severe myopathy are infrequent, but not rare side effects which may be statin-specific regarding the incidence of occurrence.

Improving microvascular perfusion with platelet glycoprotein IIb/IIIa receptor inhibition.

The hallmark of acute ST-segment elevation myocardial infarction is complete thrombotic occlusion of the infarct-related artery. Reperfusion strategies over the past 25 years have focused on the early restoration of flow in the epicardial artery. More recently, through enhanced understanding of the microvasculature, the open artery hypothesis has moved downstream to also include the complete and early restoration of microvascular flow. Fibrinolytic monotherapy has a ceiling of efficacy, but is universally available. Improvement of early artery patency can be achieved with the addition of a platelet glycoprotein IIb/IIIa receptor antagonist. Mechanical revascularization, via percutaneous coronary intervention, is superior to pharmacologic therapy, but can have limited accessibility. Perhaps the optimal strategy will involve a combination of pharmacologic and mechanical modalities.

Bivalirudin in peripheral vascular interventions: a single center experience.

Unfractionated heparin is a widely utilized anticoagulant during peripheral angioplasty procedures (PTA). In contrast to heparin, bivalirudin is a direct thrombin inhibitor with predictable anticoagulation, does not activate platelets, and inhibits both soluble and bound thrombin. The experience with bivalirudin during PTA remains limited. In this single-center prospective study, 48 consecutive patients (60.4% males, mean age 70.0 12.1) received bivalirudin as the primary anticoagulant during PTA (0.75 mg/kg bolus, 1.75 mg/kg/h during the procedure). Thirty-four (70.8%) had claudication and 6 (12.5%) had ulceration. Thrombus was angiographically seen in 3 (6.3%) patients. In-hospital serious procedural complications were limited to 2 (4.2%) (exact 95% confidence interval: (0.5%,14.3%]) patients with major bleeding; none (0.0%) of the other following endpoints occurred: death, limb loss, emergent need for revascularization of the same vessel, embolic strokes, and vascular complications (exact 95% confidence intervals: [0.0%,6.1%]). This compared favorably to previously reported data using unfractionated heparin and the same serious procedural complications endpoints from our group at the same institution (9.2%). We conclude that the use of bivalirudin during PTA appears feasible and safe. Large prospective registries are needed to confirm these findings.