Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation

Ezekowitz, Michael D.; Eikelboom, John W.; Oldgren, Jonas; Reilly, Paul; Brueckmann, Martina; Kent, Anthony P.; Pogue, Janice; Spahr, Judith; Clemens, Andreas; Noack, Herbert; Diener, Hans‐Christoph; Wallentin, Lars; Yusuf, Salim; Connolly, Stuart J.

doi:10.1093/europace/euv312

Cited by 21 publications

(11 citation statements)

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“…Nel caso del paziente descritto, a elevato rischio sia trombotico sia emorragico, la scelta di dabigatran si è rivelata vincente anche nel lungo periodo. Come dimostrato infatti dal trial RELY-ABLE, il profilo di efficacia e sicurezza di dabigatran si mantiene sostanzialmente invariato anche a lungo termine, garantendo un'adeguata protezione dalla recidiva di eventi ischemici (Figura 2) e dallo sviluppo di eventi emorragici (Figura 3), più marcata rispettivamente con il dosaggio di 150 e 110 mg [2]. Per quanto riguarda le possibili precauzioni richieste dalla presenza di IRC di grado moderato, una sotto-analisi dello studio RE-LY ha confermato l'efficacia e la sicurezza di entrambe le dosi di dabigatran anche nei pazienti con diversi gradi di compromissione della funzionalità renale (Figura 4) [1].…”

Section: Discussioneunclassified

“…I pazienti che hanno completato lo studio RE-LY nei due bracci di trattamento con dabigatran hanno avuto accesso allo studio RELY-ABLE, che ha permesso di valutare il rischio cumulativo dopo un periodo mediano di trattamento di 4,6 anni fino a un massimo di 6,7 anni (follow-up RE-LY+RELY-ABLE). I risultati dello studio RELY-ABLE hanno dimostrato che i tassi annualizzati di tutti gli endpoint sono rimasti costanti senza problemi aggiuntivi in termini di sicurezza del trattamento nel lungo periodo [2]. I risultati di efficacia del trattamento con dabigatran sono stati confermati in varie tipologie di pazienti da numerose sotto-analisi della popolazione dello studio RE-LY (per es.…”

Section: Introduzioneunclassified

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Atrial fibrillation in patient with high thrombotic risk: which therapy?

Dell’Era

2018

abtpn

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IntroduzioneLo studio RE-LY costituisce una pietra miliare nello sviluppo clinico di dabigatran. Lo studio, randomizzato, ha confrontato, per un periodo complessivo di 2 anni, l'efficacia di warfarin e due dosi di dabigatran (150 e 110 mg) in più di 18.000 pazienti con fibrillazione atriale (FA) pregressa a rischio di ictus, dimostrando la non inferiorità rispetto a warfarin di entrambe le dosi di dabigatran in termini di incidenza di ictus o embolismo sistemico (endpoint primario). Nello specifico, nel braccio di pazienti in trattamento con dabigatran 150 mg si è avuta una riduzione statisticamente significativa di ictus ed embolia sistemica, sanguinamenti intracranici e pericolosi per la vita rispetto al braccio dei pazienti in trattamento con warfarin; simili i tassi di emorragia maggiore.Nel braccio di pazienti in trattamento con dabigatran 110 mg è risultato un tasso simile di ictus ed embolia sistemica rispetto al braccio di pazienti in trattamento con warfarin, e una riduzione significativa dei sanguinamenti maggiori, pericolosi per la vita e intracranici [1]. I pazienti che hanno completato lo studio RE-LY nei due bracci di trattamento con dabigatran hanno avuto accesso allo studio RELY-ABLE, che ha permesso di valutare il rischio cumulativo dopo un periodo mediano di trattamento di 4,6 anni fino a un massimo di 6,7 anni (follow-up RE-LY+RELY-ABLE). I risultati dello studio RELY-ABLE hanno dimostrato che i tassi annualizzati di tutti gli endpoint sono rimasti costanti senza problemi aggiuntivi in termini di sicurezza del trattamento nel lungo periodo [2]. I risultati di efficacia del trattamento con dabigatran sono stati confermati in varie tipologie di pazienti da numerose sotto-analisi della popolazione dello studio RE-LY (per es. sotto-analisi basate sui punteggi CHADS 2 e CHA 2 DS 2 -VASc, pazienti naïve o no al trattamento con antagonisti della vitamina K, tipo di FA, presenza di comorbilità quali diabete, ipertensione, anemia, ictus pregresso, condizioni diverse di funzionalità renale ecc.). I risultati di queste sotto-analisi supportano l'utilizzo di dabigatran in un'ampia varietà di situazioni cliniche, caratterizzate da diversi gradi di rischio trombotico

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Section: Discussioneunclassified

Section: Introduzioneunclassified

Atrial fibrillation in patient with high thrombotic risk: which therapy?

Dell’Era

2018

abtpn

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“…However, a 150 mg dosage was more effective, while a 110 mg dosage was associated with lower major bleeding [14]. Moreover, intracerebral hemorrhage was lower in both groups.…”

Section: Discussionmentioning

confidence: 99%

Bleeding events associated with a low dose (110 mg) versus a high dose (150 mg) of dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis

Bundhun

Chaudhary

2017

BMC Cardiovasc Disord

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BackgroundThe newer oral anticoagulant dabigatran is considered to be more beneficial in patients with non-valvular Atrial Fibrillation (AF) when compared to warfarin. However, because bleeding events which are associated with a low dose (110 mg) versus a high dose (150 mg) of dabigatran have seldom been compared, we aimed to systematically solve this important issue through this meta-analysis.MethodsEnglish publications comparing 110 mg with 150 mg dabigatran in patients who were treated for AF were electronically searched through medical databases. Bleeding outcomes were the major clinical endpoints to be assessed. Odds Ratios (OR) and 95% Confidence Intervals (CIs) for each subgroup were calculated and the main analysis was carried out by the latest version of the RevMan 5.3 software.ResultsTwenty-nine thousand two hundred and sixty-four (29,264) patients were included in this meta-analysis. Fifteen thousand eight hundred and forty-eight (15,848) patients were treated with 110 mg dabigatran whereas 13,416 patients were treated with 150 mg dabigatran. 110 mg dabigatran was associated with a significantly lower rate of minor bleeding (OR: 1.19, 95% CI: 1.10–1.27; P < 0.00001). A similar rate of fatal and major bleeding was observed with both dosages (OR: 1.12, 95% CI: 0.69–1.82; P = 0.65) and (OR: 1.09, 95% CI: 0.86–1.37; P = 0.49) respectively. However, ischemic stroke insignificantly favored a higher dose of dabigatran, (OR: 0.77, 95% CI: 0.51–1.16; P = 0.21). In addition, this analysis showed mortality to significantly favor 150 mg of dabigatran (OR: 0.41, 95% CI: 0.34–0.50; P < 0.00001).ConclusionNo significant differences in major and fatal bleedings were observed with 110 mg versus 150 mg dabigatran. However, 110 mg dabigatran was associated with a significantly lower risk of minor bleeding. These results should further be confirmed in future trials.

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“…During the 6.7 years of follow-up to RE-LY in the RELY-ABLE trial, dyspepsia symptoms were reported in 602 (10.0%) and 569 (9.4%) patients receiving DE 110-mg and DE 150-mg, respectively [12]. As part of this long-term follow-up trial, the patients also completed a questionnaire designed to identify strategies employed to relieve their dyspepsia symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…As part of this long-term follow-up trial, the patients also completed a questionnaire designed to identify strategies employed to relieve their dyspepsia symptoms. Use of a proton pump inhibitor or taking dabigatran with meals were the strategies most commonly used, leading to symptomatic improvement in more than 85% of patients who reported these symptoms [12]. …”

Section: Discussionmentioning

confidence: 99%

A Prospective, Randomized, Open-Label Study to Evaluate Two Management Strategies for Gastrointestinal Symptoms in Patients Newly on Treatment with Dabigatran

2016

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IntroductionIn the pivotal RE-LY trial, dabigatran etexilate (DE) at the dose of 150-mg twice daily (BID), significantly reduced total stroke and ischemic stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF), while the 110-mg BID dose had efficacy equivalent to warfarin, and major bleeds were significantly reduced. Both DE regimens were generally well tolerated; however, approximately 4% of the patients discontinued treatment with DE due to gastrointestinal (GI) discomfort.MethodsClinical trial NCT01493557 was a multicenter, randomized, active control, open-label study to assess the efficacy of two simple GI symptom (GIS) management strategies in DE-treated patients who developed GIS: (1) concurrent treatment with the proton pump inhibitor pantoprazole (DE-P), or (2) ingestion of DE after a meal (DE-M). Patients were initially randomized to either GIS management strategy. If the first did not resolve their GIS, patients had the option to “add on” the alternative strategy.ResultsA total of 1067 patients with NVAF received DE therapy BID for 3 months (United States, 150-mg or 75-mg; Canada, 150-mg or 110-mg). Of these, 117 (11%) patients reported GIS and were randomized to one of two GIS management strategies. At 4 weeks, a significantly higher rate of complete or partial effectiveness was observed in patients on DE-P than in those receiving DE-M, [50/58 (86.2%) versus 40/59 (67.8%), respectively; p = 0.0273]. Patients with ongoing GIS were asked to “add on” the alternate strategy for an additional 4 weeks. Overall, 92/117 (78.6%) of randomized patients experienced complete or partial effectiveness using either the initial strategy or a combination of the two strategies: DE-P, 47 (81.0%); and DE-M, 45 (76.3%, no significant difference) (by initial strategy).ConclusionThe majority of patients enrolled either did not experience GIS at all, or their GIS resolved using either one individually, or a combination of the two strategies described.Trial registration http://www.ClinicalTrials.gov identifier: NCT01493557.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-016-0071-5) contains supplementary material, which is available to authorized users.

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Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation

Abstract: Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.

Cited by 21 publications

References 14 publications

Atrial fibrillation in patient with high thrombotic risk: which therapy?

Atrial fibrillation in patient with high thrombotic risk: which therapy?

Bleeding events associated with a low dose (110 mg) versus a high dose (150 mg) of dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis

A Prospective, Randomized, Open-Label Study to Evaluate Two Management Strategies for Gastrointestinal Symptoms in Patients Newly on Treatment with Dabigatran

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