Early pain reduction can predict treatment response: results of integrated efficacy analyses of a once-daily gastroretentive formulation of gabapentin in patients with postherpetic neuralgia.

OBJECTIVE: The objectives of this study were to identify and determine the validity of early decision criteria following once-daily gastroretentive gabapentin (G-GR) treatment in patients with postherpetic neuralgia (PHN). DESIGN: In two placebo-controlled studies, 279 patients were randomized to 1,800 mg G-GR and 270 to placebo with the evening meal; patients underwent a 2-week dose titration, followed by 8 weeks of stable dosing, and 1 week of dose tapering. Patients. Adults with PHN for ≥6 months and an average baseline Numerical Pain Rating Scale (NPRS) score of ≥4 were included in the study. OUTCOME MEASURES: Percent change from baseline to week 10 in NPRS scores and the percentage of responders (defined as ≥30% reduction in NPRS scores from baseline to week 10) were determined. METHODS: Patients randomized to G-GR were categorized at each week based on their percent pain reduction up to that week, and for each category, the percentage of week 10 responders was computed. For several early-improvement criteria, the percentage of week 10 responders, odds ratios for achieving week 10 treatment response, sensitivity, and specificity were calculated. RESULTS: There was a significant positive association between early pain reduction and week 10 treatment response. Pain reduction of <10% at week 5 of G-GR treatment was the best early predictor of lack of endpoint response, with only 8% of these patients moving on to become week 10 treatment responders. CONCLUSIONS: Early response was a reliable predictor of final response. This approach holds promise for aiding clinicians in decision making regarding the need for alternative or supplemental treatment during G-GR therapy for PHN.

A multicenter risk index for atrial fibrillation after cardiac surgery.

CONTEXT: Atrial fibrillation is a common, but potentially preventable, complication following coronary artery bypass graft (CABG) surgery. OBJECTIVES: To assess the nature and consequences of atrial fibrillation after CABG surgery and to develop a comprehensive risk index that can better identify patients at risk for atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study of 4657 patients undergoing CABG surgery between November 1996 and June 2000 at 70 centers located within 17 countries, selected using a systematic sampling technique. From a derivation cohort of 3093 patients, associations between predictor variables and postoperative atrial fibrillation were identified to develop a risk model, which was assessed in a validation cohort of 1564 patients. MAIN OUTCOME MEASURE: New-onset atrial fibrillation after CABG surgery. RESULTS: A total of 1503 patients (32.3%) developed atrial fibrillation after CABG surgery. Postoperative atrial fibrillation was associated with subsequent greater resource use as well as with cognitive changes, renal dysfunction, and infection. Among patients in the derivation cohort, risk factors associated with atrial fibrillation were advanced age (odds ratio [OR] for 10-year increase, 1.75; 95% confidence interval [CI], 1.59-1.93); history of atrial fibrillation (OR, 2.11; 95% CI, 1.57-2.85) or chronic obstructive pulmonary disease (OR, 1.43; 95% CI, 1.09-1.87); valve surgery (OR, 1.74; 95% CI, 1.31-2.32); and postoperative withdrawal of a beta-blocker (OR, 1.91; 95% CI, 1.52-2.40) or an angiotensin-converting enzyme (ACE) inhibitor (OR 1.69; 95% CI, 1.38-2.08). Conversely, reduced risk was associated with postoperative administration of beta-blockers (OR, 0.32; 95% CI, 0.22-0.46), ACE inhibitors (OR, 0.62; 95% CI, 0.48-0.79), potassium supplementation (OR, 0.53; 95% CI, 0.42-0.68), and nonsteroidal anti-inflammatory drugs (OR, 0.49; 95% CI, 0.40-0.60). The resulting multivariable risk index had adequate discriminative power with an area under the receiver operating characteristic (ROC) curve of 0.77 in the validation sample. Forty-three percent (640/1503) of patients who had atrial fibrillation after CABG surgery experienced more than 1 episode of atrial fibrillation. Predictors of recurrent atrial fibrillation included older age, history of congestive heart failure, left ventricular hypertrophy, aortic atherosclerosis, bicaval venous cannulation, withdrawal of ACE inhibitor or beta-blocker therapy, and use of amiodarone or digoxin (area under the ROC curve of 0.66). Patients with recurrent atrial fibrillation had longer hospital stays and experienced greater infectious, renal, and neurological complications than those with a single episode. CONCLUSIONS: We have developed and validated models predicting the occurrence of atrial fibrillation after CABG surgery based on an analysis of a large multicenter international cohort. Our findings suggest that treatment with beta-blockers, ACE inhibitors, and/or nonsteroidal anti-inflammatory drugs may offer protection. Atrial fibrillation after CABG surgery is associated with important complications.

Prevalence of risk factors, and not gender per se, determines short- and long-term survival after coronary artery bypass surgery.

OBJECTIVE: Much attention has been directed towards female gender as an independent risk factor for in-hospital mortality after coronary artery bypass grafting surgery; however, the effects of surgery are known to persist for 6 months or more. Studies that have compared postoperative survival in women and men beyond hospital discharge report disparate results with regard to the independent effect of gender per se on ultimate survival. DESIGN: This investigation was a prospective, observational study. SETTING: The study was a multicenter investigation involving 24 US medical centers. PARTICIPANTS: There were 2,048 patients undergoing isolated coronary artery bypass graft surgery enrolled between September 1991 and September 1993 and after discharge. INTERVENTIONS: There were no interventions with this prospective observational study. MEASUREMENTS AND MAIN RESULTS: Preoperative demographic variables, medical history, and angiographic data were collected for each patient at the time of enrollment. Patients' vital status through the National Death Index up to August 31, 1998, were added to assess postoperative long-term survival. For survivorship analysis, the Kaplan-Meier product-limit method was used with Cox regression model. Survivorship analyses were performed separately and in combination on mortality within 30 days and 6 months of coronary artery bypass graft surgery and during the entire postoperative follow-up period. Among women, preoperative disease status, as expected, was more severe than that in men. Women were older (p = 0.0001) and had more comorbidity, such as congestive heart failure (p = 0.0019), diabetes (p = 0.0001), anemia, and hypertension (p = 0.0001). After surgery, unadjusted survival of 6 months and 5 years in women was worse than that in men. However, there were no gender-related differences in short- or long-term survival after adjusting for covariates in the multivariate model. Preoperative conditions, such as congestive heart failure, anemia, diabetes, and advanced age, are indicative of greater risk in both women and men for lower survival after coronary artery bypass graft surgery. CONCLUSIONS: Disease prevalence in women, and not gender per se, affects mid- and long-term survival after cardiac surgery. Attention, therefore, should be focused on efforts to reduce or modify such disease prevalence earlier in women, which may in turn allow longer survival after surgical intervention. Differences in postoperative survival between women and men were related to the gender differences in the distribution of preoperative risk factors.

Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery.

OBJECTIVE: Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients. We prospectively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a randomized clinical trial. METHODS: A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States, Canada, Germany, and the United Kingdom participated in this multicenter, phase III, placebo-controlled, double-blind, randomized, parallel-group trial. Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively. Intravenous study drug (40 mg) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days. Subsequently, oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days. Patient-controlled analgesia with morphine, oral opioids, or acetaminophen was available as required. Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use. Additional efficacy evaluations included daily pain intensity, patient and physician global evaluation of study medication, and pain effect on quality of life. Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period. RESULTS: Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour (P =.009), 24- to 48-hour (P =.017), 72- to 96-hour (P =.002), 96- to 120-hour (P =.004), and 120- to 144-hour (P =.037) periods. Both patients (P <.001) and physicians (P <.001) evaluated the study medication as significantly better than control therapy. The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days. Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19.0%, 59/311 patients) than in control patients (9.9%, 15/151 patients; P =.015). Regarding individual serious adverse events, a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients (10 [3.2%]) versus control patients (0 [0%]) (P =.035). The incidences of other individual serious adverse events, including cerebrovascular complications, myocardial infarction, and renal dysfunction, were proportionally greater but not significantly different between the groups. CONCLUSIONS: In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.