Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial

Introduction

Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC).

Methods

The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH).

Results

The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6–4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44–1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31–0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34–1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18–1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups.

Conclusion

During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.     

Anti-ulcer activity of crude alcoholic extract of Toona ciliata Roemer (heart wood)

The ethanol extract of Toona ciliata Roemer (heart wood) was evaluated for its anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer (antisecretory), HCl-ethanol induced ulcer (cytoprotective) and water immersion stress induced ulcer in rats. We found that Toona ciliata extract at a dose of 300mg/kg p.o. markedly decrease the incidence of ulcers in all the three models. Ethanol extract of Toona ciliata showed significant reduction in gastric volume, free acidity, total acidity and ulcer index. The plant extract also showed gastro protective activity (52.94%), whereas standard drug sucralfate showed 94.85%. Toona ciliata extract showed protection index 43.0% in water immersion stress induced ulcer, whereas standard drug omeprazole showed protection index 100%.     

Nonsteroidal anti-inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD

The objective of this study was to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and the development of breast cancer, and to assess whether this association differed by estrogen receptor (ER) subtype. Data were analyzed from 15,651 women participating in CLUE II, a cohort study initiated in 1989 in Washington County, MD. Medication data were collected at baseline in 1989 and in 1996. Incident cases of invasive breast cancer occurring from baseline to March 27, 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryland State Cancer Registry. Cox proportional hazards modeling was used to calculate the risk ratios (RR) and 95% confidence intervals (95% CI) for breast cancer associated with medication use. Among women in the CLUE II cohort, 418 invasive breast cancer cases were identified during the follow-up period. The results showed that self-reported use of NSAIDs in both 1989 and in 1996 was associated with a 50% reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 (RR = 0.50; 95% CI 0.28, 0.91). The protective association between NSAID use and the risk of developing breast cancer was consistent among ER-positive and ER-negative breast cancers, although only the RR for ER-positive breast cancer was statistically significant. Overall, findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER-positive and ER-negative tumors.     

Puerperal tetanus.

Fifty cases of puerperal tetanus were studied. It constituted 6.66% of total cases of tetanus with overall mortality of 52% which was higher in cases with incubation period of 14 days or less, period of onset 48 hours or less, higher grades, cases with temperature more than 37.7 degrees C and patients with respiratory complications. Significantly higher mortality rate after 48 hours signifies the need of effective local control of infection to improve prognosis. Prevention, early detection and prompt treatment of respiratory complications which is the main cause of death may further reduce mortality rate in these patients.     

Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

Reflux esophagitis (RE) and Barrett’s esophagus (BE) belong to the most common esophageal complications of gastroesophageal reflux disease. Glutathione S-transferase (GST) enzymes play an important role in cellular protection against oxidative stress and toxic foreign chemicals. Therefore, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes could influence susceptibility to RE and BE. GSTM1, GSTT1 and GSTP1 loci were analyzed by PCR-based methods in 64 patients with RE (and an additional group of 22 subjects with BE as the fourth grade of esophagitis) and 173 unrelated controls. There were no significant differences in the distributions of GSTM1 and GSTT1 genotypes between the controls and patients with RE or BE. Similarly, frequencies of GSTP1 alleles were non-significantly different between the control and RE groups. However, GSTP1 B allele carriers were more frequent among the patients with BE compared to those in the reflux esophagitis group (P = 0.04, OR = 2.10, 95% CI 0.99–4.44) and most significantly when compared to the controls (P = 0.0067, P _corr < 0.05, OR = 2.56, 95%CI 1.30–5.05). Although the GSTM1 and GSTT1 genes did not show any relationship with reflux disease, the GSTP1 gene might be one of the risk factors associated with susceptibility to RE, especially to BE.