Platelet inhibition with cangrelor in patients undergoing PCI.

BACKGROUND: Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition. METHODS: We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. RESULTS: We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14). CONCLUSIONS: Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)

Effect of Metoprolol CR/XL on pulmonary artery pressure in chronic heart failure patients assessed by an implanted ultrasonic device with special emphasis on diurnal variation and exercise capacity.

OBJECTIVE: We evaluated the impact of Metoprolol CR/XL on the diurnal and exercise induced variation on Pulmonary Artery Pressure (PAP) in patients with Chronic Heart Failure (CHF) by implanted ultrasonic device. BACKGROUND: Metoprolol produces haemodynamic and clinical benefits in patients with chronic heart failure and improves survival rate. There is limited information about their effect on PAP, its diurnal and exercise induced variation in heart failure. This study evaluates the diurnal variation and effects of exercise capacity on PAP and impact of Metoprolol CR/XL (XL) on these variations on PAP in CHF patients. METHODS: In this first-in-man study, ten NYHA class III/IV patients were implanted with an ultrasonic pressure-monitoring device, followed a month later by loading with MXL 25 mg/day and uptitrated every two weeks to 200 mg/day. PAP was measured at each follow up. Diurnal variation was evaluated at baseline (no MXL), 100, and 200 mg/day MXL. Treadmill Test (TMT) was performed before and at each uptitration. Echocardiography was performed at one year. RESULTS: Uptitrating MXL caused a slight initial rise in PAP, followed by a subsequent decrease on reaching 200 mg/day dose. One patient showed repeated symptomatic rise in PAP indicating MXL intolerance and was discontinued from the uptitration. The nocturnal rise in PAP at baseline was reduced on reaching 200 mg/day MXL dose. Uptitrating MXL to 200mg7divide;day improved exercise time and metabolic equivalent tasks (METS) with no significant change in post TMT PAP. Ejection fraction also improved at one-year follow-up. CONCLUSIONS: PAP increases post exercise and diurnally in CHF patients. Slow and careful uptitration of MXL with simultaneous non-invasive monitoring of PAP may benefit in nocturnal rise and exercise capacity in CHF patients.

Efficacy of PercuSurge in acute myocardial infarction patients undergoing revascularization with a special emphasis on procedural time.

AIM: To evaluate the efficacy of the PercuSurge Guardwire(R) Plus Temporary Occlusion and Aspiration System, the actual procedural time involved and long-term follow-up in acute MI patients undergoing primary/rescue percutaneous coronary intervention (PCI). METHODS & RESULTS: It was a single centred, prospective study in 67 prospective AMI patients undergoing PCI. They were divided randomly into two groups depending on whether PercuSurge was used (n=30) or not used (control n=37) during PCI. Final TIMI flow, TMP grade and the time involved in or necessary for various steps of the PCI were recorded. PercuSurge showed significantly greater achievement of TIMI III flow and TMP III grade (p<0.01). Its use was associated with less total procedural time (p<0.05). The time required from guidewire crossing to stent placement; from guidewire crossing to TIMI III flow and from predilatation/stent placement to optimal TIMI flow was significantly reduced with its use (p<0.05 for all). Slow/no-reflow was significantly reduced (p<0.001), thus reducing intracoronary vasodilators and GP IIb/IIIa antagonists requirements. A 2 years' follow-up revealed four deaths in control and one death in PercuSurge group. CONCLUSION: PercuSurge reduced the total procedural time with better and faster optimal TIMI flow and TMP grade in primary/rescue PCI and was associated with less long term events.

Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions.

OBJECTIVE: To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors, especially plasma fibrinogen, in patients with acute coronary syndrome (ACS) requiring percutaneous coronary interventions. METHODS: A randomized, non-blinded, prospective study with parallel group design. One hundred two ACS patients who underwent angioplasty were randomly assigned to atorvastatin (20 mg/day, n=25), simvastatin (40 mg/day, n=27), atorvastatin-fenofibrate (10 mg/day-200 mg/day) combination (n=25) or simvastatin-fenofibrate (20 mg/day-200 mg/day) combination (n=25). The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments. RESULTS: All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines. The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels, and caused an increase in high-density lipoprotein levels. All the treatment groups showed a significant decrease in the plasma fibrinogen levels. Plasma fibrinogen did not correlate with study parameters such as age, body weight, hemo-dynamic characteristics and lipoprotein levels. Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels. CONCLUSIONS: The addition of fenofibrate to statins seems to be beneficial in patients with ACS. Statins decreased plasma fibrinogen significantly, contrary to results from various reports, and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen.

Quantification of the effect of clopidogrel on enzymatic infarct size related to a percutaneous coronary intervention in patients with acute coronary syndromes: insights from the CHAMPION percutaneous coronary intervention trial.

OBJECTIVES: Using data from the CHAMPION percutaneous coronary intervention (PCI), we determined the relationship between clopidogrel started at least 5 days before PCI (maintenance of clopidogrel) and PCI-related enzymatic infarct size. BACKGROUND: Clopidogrel is recommended in patients with acute coronary syndrome (ACS) managed with PCI, but its effect on PCI-related myonecrosis in contemporary patients has not been quantified. PATIENTS AND METHODS: Patients with ACS (with or without ST-segment elevation) who underwent PCI and had at least three creatine kinase-MB (CK-MB) samples after PCI were included. Enzymatic infarct size was defined as the peak CK-MB concentration indexed by its upper limit of normal. Associations between maintenance clopidogrel and enzymatic infarct size were explored using multivariable linear regression (with and without missing data imputation) and propensity score analysis using inverse probability weighting. RESULTS: Of 8877 patients randomized, 6327 (71.3%) were included (median age 61 years, 73% male, 13% ACS with ST-segment elevation). Of these 6327 patients, 2015 (31.8%) were on maintenance clopidogrel. After multivariable adjustment, maintenance clopidogrel was associated with a reduction in enzymatic infarct size {ß=-0.63; 47% decrease in peak CK-MB [95% confidence interval (CI) 35, 56%]}. Multivariable linear regression with multiple imputations and inverse probability weighting propensity score analysis yielded similar results, with maintenance clopidogrel associated with 44% (95% CI 33, 53%) and 29% (95% CI 24, 33%) infarct size reductions. CONCLUSION: In this subgroup analysis of modern ACS patients, clopidogrel maintenance was independently associated with smaller enzymatic infarct size after PCI. These results are consistent with previous observations suggesting a benefit of clopidogrel on the procedural outcome and quantify this benefit.

Ovalum CiTop Expander: a novel guidewire for crossing coronary chronic total occlusions--first-in-man (FIM) experience.

AIMS: To evaluate the safety and efficacy of the CiTop Expander guidewire in attempting to cross through chronic total occlusion in CAD patients with various coronary dimensions and morphology. Although chronic total occlusions are encountered frequently in patients with coronary artery disease, an effective strategy to deal with them has yet to be devised. Various new guidewires have been designed in an attempt to negotiate chronic occlusions successfully. The aim of the CiTop Expander guidewire is to improve the success rate of chronic total occlusion (CTO) recanalisation. METHODS AND RESULTS: Ten consecutive male or female patients between 21 and 80 years of age, with no significant comorbidities and with angiographic documented chronic total occlusion (> 1 month) showing distal TIMI flow 0, or a prior failed guidewire attempted CTO were included in the study. The endpoints analysed were technical success (crossing of CTO by placement of CiTop Expander distal to occlusion with no device related major complications), angiographic success (<20% residual stenosis and TIMI flow grade 3), and clinical success. The basic features of the novel guidewire and its assessment of compatibility with other cathlab equipments were also recorded. The mean (+/- SD) age of the all male patient group was 53.6+/-9 years. The mean (+/-SD) lesion diameter and length was 3.1+/-0.4 mm and 20.4+/-7.9 mm, respectively, while the mean (+/-SD) age of occlusion was 25.5+/-26.8 months. Technical and angiographic successes were obtained in seven patients (70%). No events were recorded within seven days and 30-days follow-up after discharge. CONCLUSIONS: The CiTop Expander guidewire was found to be efficacious and safe for use in recanalisation of chronically occluded coronary arteries in this initial experience.

Wireless acoustic communication with a miniature pressure sensor in the pulmonary artery for disease surveillance and therapy of patients with congestive heart failure.

OBJECTIVES: The purpose of this study was to examine the feasibility of repeated pulmonary artery (PA) pressure determinations using a newly developed acoustic wireless implanted communication system. BACKGROUND: Congestive heart failure management strategies based on monitored intracardiac hemodynamics in patients receiving the best-available therapy may improve outcome. Although electromagnetic communication requires a large antenna for sufficient energy transfer, acoustic energy readily penetrates deep into the body, uses little energy, and uses small internal transducers for bidirectional operation. METHODS: A miniature device was developed and implanted using right heart catheterization. The ability to obtain PA pressure from the implant using wireless acoustic communication was examined in 8 pigs and 10 patients with congestive heart failure. Macroscopic and histopathologic examinations were performed at 6 months after implantation. The accuracy of PA pressure measurement was determined by comparison with simultaneous pressures from a Millar catheter. RESULTS: The device was successfully implanted in the PA using right heart catheterization. There were no implantation or later device-related complications. Pulmonary artery pressure tracings were repeatedly obtained from all implants. Normal reactions to intravascular implant were observed macroscopically and in histologic sections. Standard deviations of the difference between implant and Millar PA diastolic pressure were 1.45 and 1.2 mm Hg (animals and humans, respectively). Data were useful for patient management. CONCLUSIONS: This pilot study demonstrates, for the first time, that acoustic wireless communication with a miniature implanted sensor is feasible and provides repeated PA pressure measurement. This feat makes possible multiple novel applications for monitoring and therapeutic interventions based on measurements from deeply implanted devices.

Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study.

OBJECTIVES: This study sought to evaluate the safety of the Coronary Sinus Reducer (Neovasc Medical, Inc., Or Yehuda, Israel) as a potential alternate therapy for patients with refractory angina who are not candidates for conventional revascularization procedures. BACKGROUND: Increased coronary sinus (CS) pressure can reduce myocardial ischemia by redistribution of blood from nonischemic to ischemic territories. The Coronary Sinus Reducer is a percutaneous implantable device designed to establish CS narrowing and to elevate CS pressure. In preclinical experiments, implantation of the Reducer was safe and was associated with improved ischemic parameters. In the present study, the safety and feasibility of the Coronary Sinus Reducer was evaluated in patients with refractory angina who were not candidates for revascularization. METHODS: Fifteen coronary artery disease patients with severe angina and reversible ischemia were electively treated with the Reducer. Clinical evaluation, dobutamine echocardiography, thallium single-photon emission computed tomography, and administration of an angina questionnaire were performed before and 6 months after implantation. Cardiac computed tomography was performed 2 days and 6 months after implantation. RESULTS: All procedures were completed successfully. No procedure-related adverse events occurred during the periprocedural and the follow-up periods. Angina score improved in 12 of 14 patients. Average Canadian Cardiovascular Society score was 3.07 at baseline and 1.64 at follow-up (n = 14, p < 0.0001). Stress-induced ST-segment depression was reduced in 6 of 9 patients and was eliminated in 2 of these 6 (p = 0.047). The extent and severity of myocardial ischemia by dobutamine echocardiography and by thallium single-photon emission computed tomography was reduced (p = 0.004 [n = 13] and p = 0.042 [n = 10], respectively). CONCLUSIONS: Implantation of the Coronary Sinus Reducer is feasible and safe. These findings, along with the clinical improvement observed, support further evaluation of the Reducer as an alternative treatment for patients with chronic refractory angina who are not candidates for coronary revascularization.

Intracoronary boluses of adenosine and sodium nitroprusside in combination reverses slow/no-reflow during angioplasty: a clinical scenario of ischemic preconditioning.

No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 microg/bolus) or the combination of adenosine (12 microg/bolus) and sodium nitroprusside (50 microg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persistent in 70% patients receiving saline solution, 31% patients receiving adenosine, and 4% patient receiving the combination. IC injection with saline solution did not produce improvement in TIMI flow or TMP grade. IC injection with combination resulted in greater improvement of TIMI flow and TMP grade. The crossover of patients with no-reflow in saline solution group or adenosine with combination treatment was associated with reestablishment of TIMI II in 4 and TIMI III in 20 patients. Our data suggest that combination therapy of adenosine and nitroprusside is safe and provides better improvement in coronary flow and MACE as compared with IC adenosine alone in cases of impaired flow during coronary interventions.