The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.

BACKGROUND: Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. METHODS: Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]). RESULTS: Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). CONCLUSIONS: Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.

Increased complication rates of cardiac rhythm management devices in ESRD patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a high incidence of sudden cardiac death and may benefit from implantable cardioverter defibrillators (ICDs). However, ESRD also may predispose patients to device-related complications, potentially offsetting some of the benefits of prophylactic ICD placement. The purpose of this study is to compare the incidence of complications after cardiac rhythm management device (CRMD) implantation in patients with and without ESRD. METHODS: An observational study was performed on 41 patients with ESRD and 123 controls without ESRD who had a CRMD (permanent pacemaker or ICD) implanted at a single institution from 1998 to 2005. Controls were matched for age, sex, type of device, and calendar year of device implantation. Primary and secondary end points were any complication and complications requiring intervention, respectively. RESULTS: 23 complications occurred in 16 of 41 patients with ESRD (39%) versus 13 complications in 13 of 123 matched controls (11%; P < 0.001). Major complications occurred in 29% of patients with ESRD versus 5% of controls (P < 0.001), whereas minor complications occurred in 17% and 6%, respectively (P < 0.03). Hematoma, thrombosis, and device-related complications, including elevated defibrillation thresholds, were more common in patients with ESRD (P < 0.05 for all), and there also was a nonsignificant trend toward greater infection risk (P = 0.1). There were no fatal complications in either group. CONCLUSIONS: Patients with ESRD had greater complication rates after CRMD implantation compared with matched controls, but these complications did not result in death. These results should be considered when evaluating patients with ESRD for prophylactic CRMD implantation, but do not support withholding such therapy.

Synthesis and properties of a novel quarternerized imidazolium [α-PW12O40]3- salt as a recoverable photo-polymerization catalyst.

A recoverable photo-polymerization catalyst based on an imidazolium and a polyoxometalate, viz., (BMIm)2(DMIm)PW12O40 (where, BMIm = 1-butyl-3-methylimidazolium, DMIm = 3,3'-dimethyl-1,1'-diimidazolium) is reported. It catalyzes photo-polymerization of several industrially important monomers like styrene, methyl methacrylate, butyl methacrylate and vinyl acetate. The catalyst is recoverable and hence can be reused. The molecular weight and polydispersity index can be controlled reasonably and a reaction pathway is proposed. The synthesis of this novel catalyst is reported and the catalyst has been characterized using standard techniques such as single crystal X-ray diffraction studies, cyclic voltammetry and various spectroscopic methods such as Fourier transform infrared spectroscopy, (1)H NMR spectroscopy, EPR spectroscopy and UV-Vis spectroscopy. DFT calculations have been used to explain the catalyst's photo-chemical activity.

Use of clopidogrel in the reduction of myocardial damage during percutaneous coronary intervention.

It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI). Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of clopidogrel is considered to be at least 300 mg given 6 to 15 hours prior to PCI but there is considerable evidence to suggest that a loading dose of 600 mg given 2 to 6 hours prior to PCI may be more efficacious in limiting post-coronary intervention events. The benefit obtained from clopidogrel appears independent of and incremental to that of other antiplatelet and antithrombotic agents used during and after coronary intervention.

Clinical outcomes of patients with diabetic nephropathy randomized to clopidogrel plus aspirin versus aspirin alone (a post hoc analysis of the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance [CHARISMA] trial).

No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin. All CHARISMA patients (n = 15,603) were separated into the 3 groups: nondiabetic patients, diabetic patients without nephropathy, and diabetic patients with nephropathy. Within each group, outcomes of patients randomly assigned to clopidogrel were compared with those of patients randomly assigned to placebo. Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status. Patients with nephropathy who received clopidogrel had no difference in bleeding, but experienced significantly increased cardiovascular (CV) and overall mortality compared with those randomly assigned to placebo. There were no differences in bleeding, overall mortality, or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo. In the asymptomatic cohort, patients with nephropathy randomly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo, whereas asymptomatic patients without nephropathy randomly assigned to clopidogrel had no significant mortality difference compared with placebo. In conclusion, this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy. Additional studies are needed to investigate this possible interaction.