major bleeds enrolled in five phase III trials comparing dabigatran with warfarin in 27,419 patients treated for 6 to 36 months. There were 627 of 16,755 patients on dabigatran who had major bleeds. These patients were older, had lower creatinine clearances, and more frequently used aspirin or nonsteroid anti-inflammatory agents than those on warfarin with major bleeds (n ¼ 407 of 10,002). Thirty-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P ¼ .057). With adjustments for sex, age, weight, renal function and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran vs warfarin was 0.66 (95% confidence interval, 0.144-1.00; P ¼ .051). In dabigatran patients with major bleeds, the bleeding was more frequently treated with blood transfusions (61%) than bleeds in warfarin patients (42%; P < .001). Patients with major bleeds treated with dabigatran were less frequently treated with plasma compared to warfarin patients with major bleeds (19.8% vs 30.2%; P < .001). Patients with major bleeds had shorter stays in intensive care units if they had previously received dabigatran (mean,1.6 nights) compared with those who had received warfarin (mean, 2.7 nights; P ¼ .01).Comment: There is obviously no ideal anticoagulant agent. Despite the fact there is no reversal agent for dabigatran, outcomes of major bleeding on this drug appear no worse and are perhaps slightly better than outcomes for patients with major bleeding on warfarin. It does not appear overall resources needed to manage major bleeding on dabigatran are greater than to manage such bleeding on warfarin. It also does not appear that the prognosis after major bleeding is worse with dabigatran than with warfarin despite the lack of a reversal agent for dabigatran. Dabigatran is an alternative to warfarin with similar or superior efficacy and overall lower risk of major bleeding. Bleeding episodes can be managed satisfactorily with relatively simple measures such as drug discontinuation and transfusion of red cells. Thus, the overall safety profile of dabigatran compared to warfarin remains favorable. Nevertheless, it is still desirable to develop a specific antidote to dabigatran.

No abstract

When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12610000590066.).

This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n=79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine (n=84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P=.081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P=.021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.

Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.