Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.     

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.     

Robot-Assisted Radical Prostatectomy After Previous Prostate Surgery

Background and Objectives:

Our objective is to clarify the effect of previous transurethral resection of the prostate (TURP) or open prostatectomy (OP) on surgical, oncological, and functional outcomes after robot-assisted radical prostatectomy (RARP).

Methods:

Between August 1, 2009, and March 31, 2013, 380 patients underwent RARP. Of these, 25 patients had undergone surgery for primary bladder outlet obstruction (TURP, 20 patients; OP, 5 patents) (group 1). A match-paired analysis was performed to identify 36 patients without a history of prostate surgery with equivalent clinicopathologic characteristics to serve as a control group (group 2). Patients followed up for 12 months were assessed.

Results:

Both groups were similar with respect to preoperative characteristics, as mean age, body mass index, median prostate-specific antigen, prostate volume, clinical stage, the biopsy Gleason score, D''Amico risk, the American Society of Anesthesiologists (ASA) classification score, the International Prostate Symptom Score, continence, and potency status. RARP resulted in longer console and anastomotic time, as well as higher blood loss compared with surgery-naive patients. We noted a greater rate of urinary leakage (pelvic drainage, >4 d) in group 1 (12% vs 2,8%). The anastomotic stricture rate was significantly higher in group 1 (16% vs 2.8%). No difference was found in the pathologic stage, positive surgical margin, and nerve-sparing procedure between the groups. Biochemical recurrence was observed in 12% (group 1) and 11.1% (group 2) of patients, respectively. No significant difference was found in the continence and potency rates.

Conclusions:

RARP after TURP or OP is a challenging but oncologically promising procedure with a longer console and anastomosis time, as well as higher blood loss and higher anastomotic stricture rate.     

Laparoscopic Radical Prostatectomy Alone or With Laparoscopic Herniorrhaphy

Background and Objectives:

Prostate cancer and inguinal hernia are common health issues in men aged more than 50 years. Recently, more data are accumulating that laparoscopic radical prostatectomy (LRP) and laparoscopic inguinal hernia repair (LIHR) can be performed in the same operation. The purpose of this study was to compare patients who underwent simultaneous extraperitoneal LRP (E-LRP) and LIHR with control patients who underwent only E-LRP in a matched-pairs design.

Methods:

Medical records of 215 patients were evaluated, and 20 patients who underwent E-LRP+LIHR were compared with 40 patients who underwent only E-LRP in a matched-pairs analysis. Preoperative clinical parameters (age, body mass index, prostate-specific antigen, clinical stage, Gleason score of the prostate biopsy, and prostate volume) and operative data (operation time, duration of catheterization, length of hospital stay, estimated blood loss, time to perform the anastomosis and its quality, and the percentage of patients with bilateral lymphadenectomy) were evaluated, as well as postoperative parameters (pathological stage, Gleason score, specimen weight, follow-up duration, biochemical recurrence, complication rates, and duration of postoperative analgesic treatment).

Results:

No statistically significant differences were found in the preoperative and operative parameters between the 2 study groups. Pathological parameters and the follow-up period and complication rates were similar between the 2 groups.

Conclusion:

Performing LIHR and E-LRP during the same operation is safe and feasible in the treatment of patients with prostate cancer and inguinal hernia.