- Email: [email protected]
Intracerebral haemorrhage, atrial fibrillation, and anticoagulation
Correspondence
The RTS,S/AS01 vaccine might soon be licensed. Before RTS,S/AS01 is introduced as routine vaccination, the vaccine should be shown to have no deleterious effects compared with the placebo. We declare no competing interests.
*Peter Aaby, Amabelia Rodrigues, Poul-Erik Kofoed, Christine Stabell Benn [email protected] Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau (PA, AR); Research Centre for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, 2300 Copenhagen, Denmark (AR, CSB); and Department of Paediatrics, Kolding Hospital, Kolding, Denmark (P-EK) 1
2
3
4
5
6
7
See Editorial page 1708
1736
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 2015; 386: 31–45. Brooks A, Briét OJT, Hardy D, Steketee R, Smith TA. Simulated impact of RTS,S/AS01 vaccinations programs in the context of changing malaria transmission. PLoS One 2012; 7: e32587. Benn CS, Netea MG, Selin LK, Aaby P. A small jab—a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34: 431–39. Strategic Advisory Group of Experts on Immunization. Week Epidemiol Rec 2014; 89: 233–35. Aaby P, Jensen H, Samb B, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: re-analysis of West African studies. Lancet 2003; 361: 2183–88. Bejon P, Abdulla S, Lusingu J, et al. Response to “Poor control vaccines in two randomised trials of malaria vaccine?” Vaccine 2009; 27: 4745–46. Hamel MJ, Otieno TL, Greenwood B, for the RTS,S Synthesis and Writing Committee. The RTS,S/AS01 Phase 3 trial was not designed to show efficacy against mortality. PLoS Med 2014; published online Nov 14. http://www. plosmedicine.org/annotation/listThread. action?root=81929 (accessed May 5, 2015).
RTS,S/AS01 malaria vaccination in young infants with and without a booster was associated with vaccine efficacies of 18–36%. 1 The Lancet supports a large-scale vaccine roll-out after publication of these final results from a multicentre phase 3 study.2 We would argue for a more cautionary approach and call for additional studies before considering the inclusion of this vaccine in the routine Expanded Programme for Immunizations schedule.
First, the vaccine provides only modest and short-lived protection.1 Cost-effectiveness needs to be established to justify large-scale roll-out of a partially effective malaria vaccine in endemic countries. Second, safety of the vaccine is an issue with an unexplained excess of meningitis cases reported in the RTS,S group.1 Third, data cannot confirm yet if and how the inactivated RTS,S/AS01 will affect overall child mortality. Although live vaccines overall seem to be beneficial, inactivated vaccines have been associated with negative non-specific effects, including increased child mortality.3,4 Finally, malaria interventions in young children might lead to rebound morbidity and mortality in older age groups. Long-term follow-up studies5 were undertaken before the insecticide-treated mosquito net intervention was recommended for large-scale roll-out in endemic areas. This process should also apply to malaria vaccines. A malaria vaccine would be an important complement to existing preventive and treatment measures, but well-designed long-term studies are warranted before a decision is made to include a malaria vaccine in the Expanded Programme for Immunizations. We declare no competing interests.
*Olaf Müller, Yesim Tozan, Heiko Becher [email protected] Institute of Public Health, Medical School, RuprechtKarls-University, 69124 Heidelberg, Germany (OM); Department of Public Health, New York University, New York, NY, USA (YT); and Institute of Medical Biometry and Epidemiology, University of Hamburg, Medical School, Hamburg, Germany (HB) 1
2 3
4
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 2015; 386: 31–45. The Lancet. Vaccines: a step change in malaria prevention? Lancet 2015; 385: 1591. Benn CS, Netea MG, Selin LK, Aaby P. A small jab—a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34: 431–39. Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O. Heterologous (“nonspecific”) and sex-differential effects of vaccines: epidemiology, clinical trials, and emerging immunologic mechanisms. Clin Infect Dis 2013; 57: 283–89.
5
Louis V, Bals J, Tiendrebéogo J, et al. Long-term effects of malaria prevention with insecticide-treated mosquito nets on morbidity and mortality in African children: randomised controlled trial. Trop Med Int Health 2012; 17: 733–41.
Intracerebral haemorrhage, atrial fibrillation, and anticoagulation The Review by Freek Verheugt and colleagues (July 18, p 303) 1 provides an excellent overview of non-vitamin K antagonist oral anticoagulants (NOACs) and stroke prevention in atrial fibrillation. However, we emphasise another factor that was omitted: survivors of intracranial haemorrhage who also have atrial fibrillation. Observational studies show up to 37% of patients with an intracerebral haemorrhage have concurrent atrial fibrillation,2 with absolute numbers of patients who have anticoagulant-related intracranial haemorrhage expected to increase because of the increased use of oral anticoagulation and an ageing population.3 Should individuals with intracranial haemorrhage and atrial fibrillation be treated with anticoagulation? Recurrence of intracerebral haemorrhage can be as high as 22% at 2 years depending on the underlying cause. 4 Moreover, up to 76% of patients either die or are unable to live independently when discharged from hospital after an intracranial haemorrhage associated with oral anticoagulation.5 By contrast, observational registries, of patients with intracerebral and intracranial haemorrhage and an indication for oral anticoagulation, show that restarting oral anticoagulation treatment after an event is associated with a decrease in mortality and subsequent ischaemic stroke events, without an increase in recurrent intracerebral or intracranial haemorrhage risk.6 www.thelancet.com Vol 386 October 31, 2015
Correspondence
DW declares no competing interests. RA-SS received grants from British Heart Foundation, outside the submitted work. CJMK received grants from Dutch Heart Foundation and ASPASIA, and personal fees from Boehringer Ingelheim, outside the submitted work. GYHL has been a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Biotronik, Portola, and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi-Aventis. DJW received personal fees from Bayer, outside the submitted work.
*Duncan Wilson, Rustam Al-Shahi Salman, Catharina J M Klijn, Gregory Y H Lip, David J Werring [email protected] University College London Stroke Research Centre, Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London WC1B 3EE, UK (DW, DJW); School of Clinical Sciences, Centre for Clinical Brain Sciences, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK (RA-SS); Department of Neurology, Donders Institute for Brain Cognition & Behaviour, Center for Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands (CJMK); Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands (CJMK); University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK (GYHL); and Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark (GYHL) 1
2
3
Verheugt FW, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 2015; 386: 303–10. Horstmann S, Rizos T, Jenetzky E, Gumbinger C, Hacke W, Veltkamp R. Prevalence of atrial fibrillation in intracerebral hemorrhage. Eur J Neurol 2014; 21: 570–76. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68: 116–21.
www.thelancet.com Vol 386 October 31, 2015
4
5
6
7
Viswanathan A, Rakich SM, Engel C, et al. Antiplatelet use after intracerebral hemorrhage. Neurology 2006; 66: 206–09. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120: 700–05. Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015; 313: 824–36. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–62.
Authors’ reply We thank Duncan Wilson and colleagues for their comments about our Review.1 These authors discuss an important issue and suggest that non-vitamin K antagonist oral anticoagulants might provide a strong option to reduce ischaemic stroke in patients who have atrial fibrillation and have suffered an intracranial haemorrhage. A fundamental advantage of non-vitamin K antagonist oral anticoagulants over warfarin is the substantially lower risk of intracranial haemorrhage, 2 and this feature might be particularly important for patients at high risk of intracranial haemorrhage, including those with previous history of this disorder. FWAV received personal consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, and Bayer Healthcare. CBG received grants and personal fees from Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Daiichi Sankyo, Janssen Pharmaceuticals, and Bayer, during the conduct of the study, and grants and personal fees from GlaxoSmithKline, Sanofi-Aventis, Takeda, The Medicine’s Company, AstraZeneca, and Salix Pharmaceuticals, grants from Medtronic Foundation, Merck & Co, and Armetheon, personal fees from Hoffmann-La Roche, Eli Lilly, Ross Medical Corporation, Gilead, and Medtronic Inc, outside the submitted work.
*Freek W A Verheugt, Christopher B Granger [email protected] Heart and Lung Centre, Onze Lieve Vrouwe Gasthuis, 1091 AC Amsterdam, Netherlands (FWAV); and Duke Cardiovascular Research institute, Durham, NC, USA (CBG) 1
Verheugt FW, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 2015; 386: 303–10.
2
Ruff CT, Giugliano RP, Braunwald T, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–62.
Late-onset effects of radiation and chronic kidney disease Kamiya and colleagues (Aug 1, p 469)1 provide a timely report of the late-onset effects of wartime and accidental radiation exposure and briefly mention chronic kidney disease as a potential late-onset effect. Chronic kidney disease is a clinically significant, but underappreciated, late-onset compli cation of haemopoietic stem-cell transplantation that is often linked to total body irradiation before transplantation.2 Partial or total body exposures to radiation doses as low as 5 Gy in a single fraction are not lethal but can lead to radiation nephropathy.3 Exposures to even lower doses of radiation are associated with late cardiovascular and renal disease.4 Chronic kidney disease substantially increases human morbidity and mortality,5 and renal function should be part of the immediate and long-term follow-up of individuals who have had substantial clinical or accidental radiation exposures to parts of the body that include the kidneys.
Zephyr/Science Photo Library
NOACs might be the most attractive anticoagulant option in intracranial haemorrhage survivors, in view of their 50% lower risk of intracranial haemorrhage compared with warfarin,7 yet no published trials tackling this question exist. Only one randomised controlled trial for this topic is underway (EU Clinical Trials Register 2014-000112-33) with another planned (ISRCTN71907627). NOACs are a great leap forward in preventing stroke associated with atrial fibrillation and reducing the risk of intracranial haemorrhage. However, these drugs need to be tested in intracranial haemorrhage survivors with an indication for anticoagulation.
EPC reports grants from the US Department of Veterans Affairs. JEM reports grants from the National Institutes of Health, the American Cancer Society, and the US Department of Veterans Affairs. BLF declares no competing interests.
*Eric P Cohen, Brian L Fish, John E Moulder [email protected] Baltimore VA Medical Center and the University of Maryland School of Medicine, Baltimore, MD, USA (EPC); and Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA (BLF, JEM) 1
2
Kamiya K, Ozasa K, Akiba S, et al. Long-term effects of radiation exposure on health. Lancet 2015; 386: 469–78. Cohen EP, Pais P, Moulder JE. Chronic kidney disease after hematopoietic stem cell transplantation. Semin Nephrol 2010; 30: 627–34.
1737
The RTS,S/AS01 vaccine might soon be licensed. Before RTS,S/AS01 is introduced as routine vaccination, the vaccine should be shown to have no deleterious effects compared with the placebo. We declare no competing interests.
*Peter Aaby, Amabelia Rodrigues, Poul-Erik Kofoed, Christine Stabell Benn [email protected] Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau (PA, AR); Research Centre for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, 2300 Copenhagen, Denmark (AR, CSB); and Department of Paediatrics, Kolding Hospital, Kolding, Denmark (P-EK) 1
2
3
4
5
6
7
See Editorial page 1708
1736
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 2015; 386: 31–45. Brooks A, Briét OJT, Hardy D, Steketee R, Smith TA. Simulated impact of RTS,S/AS01 vaccinations programs in the context of changing malaria transmission. PLoS One 2012; 7: e32587. Benn CS, Netea MG, Selin LK, Aaby P. A small jab—a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34: 431–39. Strategic Advisory Group of Experts on Immunization. Week Epidemiol Rec 2014; 89: 233–35. Aaby P, Jensen H, Samb B, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: re-analysis of West African studies. Lancet 2003; 361: 2183–88. Bejon P, Abdulla S, Lusingu J, et al. Response to “Poor control vaccines in two randomised trials of malaria vaccine?” Vaccine 2009; 27: 4745–46. Hamel MJ, Otieno TL, Greenwood B, for the RTS,S Synthesis and Writing Committee. The RTS,S/AS01 Phase 3 trial was not designed to show efficacy against mortality. PLoS Med 2014; published online Nov 14. http://www. plosmedicine.org/annotation/listThread. action?root=81929 (accessed May 5, 2015).
RTS,S/AS01 malaria vaccination in young infants with and without a booster was associated with vaccine efficacies of 18–36%. 1 The Lancet supports a large-scale vaccine roll-out after publication of these final results from a multicentre phase 3 study.2 We would argue for a more cautionary approach and call for additional studies before considering the inclusion of this vaccine in the routine Expanded Programme for Immunizations schedule.
First, the vaccine provides only modest and short-lived protection.1 Cost-effectiveness needs to be established to justify large-scale roll-out of a partially effective malaria vaccine in endemic countries. Second, safety of the vaccine is an issue with an unexplained excess of meningitis cases reported in the RTS,S group.1 Third, data cannot confirm yet if and how the inactivated RTS,S/AS01 will affect overall child mortality. Although live vaccines overall seem to be beneficial, inactivated vaccines have been associated with negative non-specific effects, including increased child mortality.3,4 Finally, malaria interventions in young children might lead to rebound morbidity and mortality in older age groups. Long-term follow-up studies5 were undertaken before the insecticide-treated mosquito net intervention was recommended for large-scale roll-out in endemic areas. This process should also apply to malaria vaccines. A malaria vaccine would be an important complement to existing preventive and treatment measures, but well-designed long-term studies are warranted before a decision is made to include a malaria vaccine in the Expanded Programme for Immunizations. We declare no competing interests.
*Olaf Müller, Yesim Tozan, Heiko Becher [email protected] Institute of Public Health, Medical School, RuprechtKarls-University, 69124 Heidelberg, Germany (OM); Department of Public Health, New York University, New York, NY, USA (YT); and Institute of Medical Biometry and Epidemiology, University of Hamburg, Medical School, Hamburg, Germany (HB) 1
2 3
4
RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 2015; 386: 31–45. The Lancet. Vaccines: a step change in malaria prevention? Lancet 2015; 385: 1591. Benn CS, Netea MG, Selin LK, Aaby P. A small jab—a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34: 431–39. Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O. Heterologous (“nonspecific”) and sex-differential effects of vaccines: epidemiology, clinical trials, and emerging immunologic mechanisms. Clin Infect Dis 2013; 57: 283–89.
5
Louis V, Bals J, Tiendrebéogo J, et al. Long-term effects of malaria prevention with insecticide-treated mosquito nets on morbidity and mortality in African children: randomised controlled trial. Trop Med Int Health 2012; 17: 733–41.
Intracerebral haemorrhage, atrial fibrillation, and anticoagulation The Review by Freek Verheugt and colleagues (July 18, p 303) 1 provides an excellent overview of non-vitamin K antagonist oral anticoagulants (NOACs) and stroke prevention in atrial fibrillation. However, we emphasise another factor that was omitted: survivors of intracranial haemorrhage who also have atrial fibrillation. Observational studies show up to 37% of patients with an intracerebral haemorrhage have concurrent atrial fibrillation,2 with absolute numbers of patients who have anticoagulant-related intracranial haemorrhage expected to increase because of the increased use of oral anticoagulation and an ageing population.3 Should individuals with intracranial haemorrhage and atrial fibrillation be treated with anticoagulation? Recurrence of intracerebral haemorrhage can be as high as 22% at 2 years depending on the underlying cause. 4 Moreover, up to 76% of patients either die or are unable to live independently when discharged from hospital after an intracranial haemorrhage associated with oral anticoagulation.5 By contrast, observational registries, of patients with intracerebral and intracranial haemorrhage and an indication for oral anticoagulation, show that restarting oral anticoagulation treatment after an event is associated with a decrease in mortality and subsequent ischaemic stroke events, without an increase in recurrent intracerebral or intracranial haemorrhage risk.6 www.thelancet.com Vol 386 October 31, 2015
Correspondence
DW declares no competing interests. RA-SS received grants from British Heart Foundation, outside the submitted work. CJMK received grants from Dutch Heart Foundation and ASPASIA, and personal fees from Boehringer Ingelheim, outside the submitted work. GYHL has been a consultant for Bayer, Astellas, Merck, AstraZeneca, Sanofi, BMS/Pfizer, Biotronik, Portola, and Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi-Aventis. DJW received personal fees from Bayer, outside the submitted work.
*Duncan Wilson, Rustam Al-Shahi Salman, Catharina J M Klijn, Gregory Y H Lip, David J Werring [email protected] University College London Stroke Research Centre, Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, London WC1B 3EE, UK (DW, DJW); School of Clinical Sciences, Centre for Clinical Brain Sciences, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK (RA-SS); Department of Neurology, Donders Institute for Brain Cognition & Behaviour, Center for Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands (CJMK); Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands (CJMK); University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK (GYHL); and Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark (GYHL) 1
2
3
Verheugt FW, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 2015; 386: 303–10. Horstmann S, Rizos T, Jenetzky E, Gumbinger C, Hacke W, Veltkamp R. Prevalence of atrial fibrillation in intracerebral hemorrhage. Eur J Neurol 2014; 21: 570–76. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68: 116–21.
www.thelancet.com Vol 386 October 31, 2015
4
5
6
7
Viswanathan A, Rakich SM, Engel C, et al. Antiplatelet use after intracerebral hemorrhage. Neurology 2006; 66: 206–09. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120: 700–05. Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015; 313: 824–36. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–62.
Authors’ reply We thank Duncan Wilson and colleagues for their comments about our Review.1 These authors discuss an important issue and suggest that non-vitamin K antagonist oral anticoagulants might provide a strong option to reduce ischaemic stroke in patients who have atrial fibrillation and have suffered an intracranial haemorrhage. A fundamental advantage of non-vitamin K antagonist oral anticoagulants over warfarin is the substantially lower risk of intracranial haemorrhage, 2 and this feature might be particularly important for patients at high risk of intracranial haemorrhage, including those with previous history of this disorder. FWAV received personal consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, and Bayer Healthcare. CBG received grants and personal fees from Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Daiichi Sankyo, Janssen Pharmaceuticals, and Bayer, during the conduct of the study, and grants and personal fees from GlaxoSmithKline, Sanofi-Aventis, Takeda, The Medicine’s Company, AstraZeneca, and Salix Pharmaceuticals, grants from Medtronic Foundation, Merck & Co, and Armetheon, personal fees from Hoffmann-La Roche, Eli Lilly, Ross Medical Corporation, Gilead, and Medtronic Inc, outside the submitted work.
*Freek W A Verheugt, Christopher B Granger [email protected] Heart and Lung Centre, Onze Lieve Vrouwe Gasthuis, 1091 AC Amsterdam, Netherlands (FWAV); and Duke Cardiovascular Research institute, Durham, NC, USA (CBG) 1
Verheugt FW, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 2015; 386: 303–10.
2
Ruff CT, Giugliano RP, Braunwald T, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–62.
Late-onset effects of radiation and chronic kidney disease Kamiya and colleagues (Aug 1, p 469)1 provide a timely report of the late-onset effects of wartime and accidental radiation exposure and briefly mention chronic kidney disease as a potential late-onset effect. Chronic kidney disease is a clinically significant, but underappreciated, late-onset compli cation of haemopoietic stem-cell transplantation that is often linked to total body irradiation before transplantation.2 Partial or total body exposures to radiation doses as low as 5 Gy in a single fraction are not lethal but can lead to radiation nephropathy.3 Exposures to even lower doses of radiation are associated with late cardiovascular and renal disease.4 Chronic kidney disease substantially increases human morbidity and mortality,5 and renal function should be part of the immediate and long-term follow-up of individuals who have had substantial clinical or accidental radiation exposures to parts of the body that include the kidneys.
Zephyr/Science Photo Library
NOACs might be the most attractive anticoagulant option in intracranial haemorrhage survivors, in view of their 50% lower risk of intracranial haemorrhage compared with warfarin,7 yet no published trials tackling this question exist. Only one randomised controlled trial for this topic is underway (EU Clinical Trials Register 2014-000112-33) with another planned (ISRCTN71907627). NOACs are a great leap forward in preventing stroke associated with atrial fibrillation and reducing the risk of intracranial haemorrhage. However, these drugs need to be tested in intracranial haemorrhage survivors with an indication for anticoagulation.
EPC reports grants from the US Department of Veterans Affairs. JEM reports grants from the National Institutes of Health, the American Cancer Society, and the US Department of Veterans Affairs. BLF declares no competing interests.
*Eric P Cohen, Brian L Fish, John E Moulder [email protected] Baltimore VA Medical Center and the University of Maryland School of Medicine, Baltimore, MD, USA (EPC); and Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA (BLF, JEM) 1
2
Kamiya K, Ozasa K, Akiba S, et al. Long-term effects of radiation exposure on health. Lancet 2015; 386: 469–78. Cohen EP, Pais P, Moulder JE. Chronic kidney disease after hematopoietic stem cell transplantation. Semin Nephrol 2010; 30: 627–34.
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