Re: Early management of head injury: summary of updated NICE guidance
We have read with interest the summary of updated NICE guidance for early management of head injury.[1] Considering the criteria for computed tomography (CT) scan, Matt Heywood endorsed a letter expressing the concerns about the absence of other anticoagulants, rather than warfarin, as criterion for CT scan.[2]
Putting the things in perspective, the pharmacological effect of all these drugs impair the haemostasis by inhibiting factors from the coagulation cascade and, thereby increase the risk of bleeding.
New oral anticoagulants (NOACs) such as apixaban, dabigatran, edoxaban and rivaroxaban, have overcome some limitations presented by warfarin, and shown to be at least similar in terms of efficacy.
Regarding intracranial haemorrhage (ICH), we performed an electronic literature search to identify phase III randomized controlled trials (RCTs) evaluating the referred NOACs compared to warfarin, with at least 1 ICH event during the trial.
We found 10 RCTs with 96 610 patients (5 trials with 72 793 patients with atrial fibrillation, and 5 trials enrolling 23 817 patients with venous thromboembolism). Overall 54 853 patients were treated with NOACs and the mean follow-up was 2.2 years for atrial fibrillation (AF) and 0.92 years for venous thromboembolism (VTE) trials.
Random effects meta-analysis of these studies showed a significant relative risk reduction of ICH in patients with AF treated with NOACs (Risk Ratio [RR] 0.44; 95% Confidence Interval [95%CI] 0.35 to 0.55), with moderate heterogeneity between studies (I2=49%). Similarly the ICH risk reduction with NOACs was significant in trials with patients with VTE disease (RR 0.31; 95%CI 0.15 to 0.67; I2=0%). There was no difference between the estimates of AF and VTE trials (p=0.40). Figure 1 shows the forest plot with meta-analysis results.
Assuming similarity of relative risk reduction with NOACS across the referred conditions, the overall pooled RR of ICH with NOAC was 0.43 (95%CI 0.36 to 0.51; I2=15%).
It is true that these data do not reflect the risk of patients with head injury, but are somehow informative showing that NOACs consistently halve the risk of global ICH.
Despite the all, the global risk of bleeding including ICH is increased with any anticoagulant, therefore we agree with Heywood’s concerns.
References
1. Hodgkinson S, Pollit V, Sharpin C, Lecky F; on behalf of the Guideline Development Group. Early management of head injury: summary of updated NICE guidance. BMJ 2014;348:g104.
2. Heywood M. Computed tomography after head injury for patients taking any anticoagulant, not just warfarin? BMJ 2014;348:g1431.
Competing interests:
DC and JC do not have any competing interests. FJP had consultant and speaker fees with Astra Zeneca, Bayer and Boehringer Ingelheim. JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme.
16 February 2014
Daniel Caldeira
Assistant of Clinical Pharmacology; Cardiology trainee
João Costa, Fausto J Pinto, Joaquim J Ferreira
Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal
Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Rapid Response:
Re: Early management of head injury: summary of updated NICE guidance
We have read with interest the summary of updated NICE guidance for early management of head injury.[1] Considering the criteria for computed tomography (CT) scan, Matt Heywood endorsed a letter expressing the concerns about the absence of other anticoagulants, rather than warfarin, as criterion for CT scan.[2]
Putting the things in perspective, the pharmacological effect of all these drugs impair the haemostasis by inhibiting factors from the coagulation cascade and, thereby increase the risk of bleeding.
New oral anticoagulants (NOACs) such as apixaban, dabigatran, edoxaban and rivaroxaban, have overcome some limitations presented by warfarin, and shown to be at least similar in terms of efficacy.
Regarding intracranial haemorrhage (ICH), we performed an electronic literature search to identify phase III randomized controlled trials (RCTs) evaluating the referred NOACs compared to warfarin, with at least 1 ICH event during the trial.
We found 10 RCTs with 96 610 patients (5 trials with 72 793 patients with atrial fibrillation, and 5 trials enrolling 23 817 patients with venous thromboembolism). Overall 54 853 patients were treated with NOACs and the mean follow-up was 2.2 years for atrial fibrillation (AF) and 0.92 years for venous thromboembolism (VTE) trials.
Random effects meta-analysis of these studies showed a significant relative risk reduction of ICH in patients with AF treated with NOACs (Risk Ratio [RR] 0.44; 95% Confidence Interval [95%CI] 0.35 to 0.55), with moderate heterogeneity between studies (I2=49%). Similarly the ICH risk reduction with NOACs was significant in trials with patients with VTE disease (RR 0.31; 95%CI 0.15 to 0.67; I2=0%). There was no difference between the estimates of AF and VTE trials (p=0.40). Figure 1 shows the forest plot with meta-analysis results.
Assuming similarity of relative risk reduction with NOACS across the referred conditions, the overall pooled RR of ICH with NOAC was 0.43 (95%CI 0.36 to 0.51; I2=15%).
It is true that these data do not reflect the risk of patients with head injury, but are somehow informative showing that NOACs consistently halve the risk of global ICH.
Despite the all, the global risk of bleeding including ICH is increased with any anticoagulant, therefore we agree with Heywood’s concerns.
References
1. Hodgkinson S, Pollit V, Sharpin C, Lecky F; on behalf of the Guideline Development Group. Early management of head injury: summary of updated NICE guidance. BMJ 2014;348:g104.
2. Heywood M. Computed tomography after head injury for patients taking any anticoagulant, not just warfarin? BMJ 2014;348:g1431.
Competing interests: DC and JC do not have any competing interests. FJP had consultant and speaker fees with Astra Zeneca, Bayer and Boehringer Ingelheim. JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme.