Pub Date : 2025-02-27DOI: 10.1016/s0140-6736(24)02842-3
Francis Couturaud, Jeannot Schmidt, Olivier Sanchez, Alice Ballerie, Marie-Antoinette Sevestre, Nicolas Meneveau, Laurent Bertoletti, Jérôme Connault, Ygal Benhamou, Joël Constans, Thomas Quemeneur, François-Xavier Lapébie, Gilles Pernod, Gaël Picart, Antoine Elias, Caroline Doutrelon, Claire Neveux, Lina Khider, Pierre-Marie Roy, Stéphane Zuily, Henri HERVE
<h3>Background</h3>In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated.<h3>Methods</h3>RENOVE was a non-inferiority, investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial done in 47 hospitals in France. Ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6–24 uninterrupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were eligible. Eligible participants were categorised as having either a first unprovoked venous thromboembolism, recurrent venous thromboembolism, presence of persistent risk factors, or other clinical situations considered to be a high risk of recurrence. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2·5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily) using a centralised randomisation procedure with an interactive web response system. The sequence generation method was a computerised random number generator and was balanced by blocks of different sizes. Randomisation was stratified by centre, type of direct oral anticoagulant, and antiplatelet drug. Physicians and participants were unmasked to treatment allocation; recurrent venous thromboembolism, clinically relevant bleeding, and all-cause death were adjudicated by an independent committee blinded to treatment allocation. The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent fatal or non-fatal pulmonary embolism or isolated proximal deep vein thrombosis (non-inferiority hypothesis 90% power to exclude a hazard ratio [HR] of 1·7). The primary outcome and first two secondary outcomes were included in a hierarchical testing procedure. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT03285438</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>.<h3>Findings</h3>From Nov 2, 2017, to July 6, 2022, 2768 patients were enrolled and randomly assigned to the reduced-dose group (n=1383) or the full-dose group (n=1385). 970 (35·0%) participants were female, 1797 (65·0%) were male, and one (<0·1%) had sex not reported. Median follow-up was 37·1 months (IQR 24
{"title":"Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: a non-inferiority, multicentre, randomised, open-label, blinded endpoint trial","authors":"Francis Couturaud, Jeannot Schmidt, Olivier Sanchez, Alice Ballerie, Marie-Antoinette Sevestre, Nicolas Meneveau, Laurent Bertoletti, Jérôme Connault, Ygal Benhamou, Joël Constans, Thomas Quemeneur, François-Xavier Lapébie, Gilles Pernod, Gaël Picart, Antoine Elias, Caroline Doutrelon, Claire Neveux, Lina Khider, Pierre-Marie Roy, Stéphane Zuily, Henri HERVE","doi":"10.1016/s0140-6736(24)02842-3","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02842-3","url":null,"abstract":"<h3>Background</h3>In patients with venous thromboembolism at high risk of recurrence for whom extended treatment with direct oral anticoagulants has been indicated, the optimal dose is unknown. We aimed to assess efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants in patients in whom extended anticoagulation has been indicated.<h3>Methods</h3>RENOVE was a non-inferiority, investigator-initiated, multicentre, randomised, open-label, blinded endpoint trial done in 47 hospitals in France. Ambulatory patients aged 18 years or older with acute symptomatic venous thromboembolism (pulmonary embolism or proximal deep vein thrombosis) who had received 6–24 uninterrupted months of full-dose anticoagulation and for whom extended anticoagulation has been indicated were eligible. Eligible participants were categorised as having either a first unprovoked venous thromboembolism, recurrent venous thromboembolism, presence of persistent risk factors, or other clinical situations considered to be a high risk of recurrence. Participants were randomly assigned (1:1) to receive oral treatment with either a reduced dose of apixaban (2·5 mg twice daily) or rivaroxaban (10 mg once daily) or a full dose of apixaban (5 mg twice daily) or rivaroxaban (20 mg once daily) using a centralised randomisation procedure with an interactive web response system. The sequence generation method was a computerised random number generator and was balanced by blocks of different sizes. Randomisation was stratified by centre, type of direct oral anticoagulant, and antiplatelet drug. Physicians and participants were unmasked to treatment allocation; recurrent venous thromboembolism, clinically relevant bleeding, and all-cause death were adjudicated by an independent committee blinded to treatment allocation. The primary outcome was symptomatic recurrent venous thromboembolism, including recurrent fatal or non-fatal pulmonary embolism or isolated proximal deep vein thrombosis (non-inferiority hypothesis 90% power to exclude a hazard ratio [HR] of 1·7). The primary outcome and first two secondary outcomes were included in a hierarchical testing procedure. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03285438</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>From Nov 2, 2017, to July 6, 2022, 2768 patients were enrolled and randomly assigned to the reduced-dose group (n=1383) or the full-dose group (n=1385). 970 (35·0%) participants were female, 1797 (65·0%) were male, and one (<0·1%) had sex not reported. Median follow-up was 37·1 months (IQR 24","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/s0140-6736(25)00351-4
Rajat Khosla, Pascale Allotey
No Abstract
{"title":"Age of distrust: impact of hegemonic policy decisions on sexual and reproductive health and rights","authors":"Rajat Khosla, Pascale Allotey","doi":"10.1016/s0140-6736(25)00351-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00351-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/s0140-6736(25)00333-2
Roland Veltkamp, Eleni Korompoki, Kirsten H Harvey, Emily R Harvey, Cornelia Fießler, Uwe Malzahn, Viktoria Rücker, Joan Montaner, Valeria Caso, Igor Sibon, Peter Ringleb, Omid Halse, Klemens Hügen, Sabine Ullmann, Carolin Schuhmann, Gabriele Putz Todd, Kirsten Haas, Elena Palà, Stéphanie Debette, Morgane Lachaize, Robyn Lotto
<h3>Background</h3>Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage.<h3>Methods</h3>PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT03996772</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is complete.<h3>Findings</h3>Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p<0·0001). The rate of all ischaemic stroke events was 0·83 (95% CI 0·14–2·57) per 100 patient-years in the DOAC group versus 8·60 (5·43–12·80) per 100 patient-years in the no anticoagulant group. For first recurrent intracerebral haemorrhage, the DOAC group did not meet the prespecified HR for the non-inferiority margin of less than 1·735 (HR 10·89 [90% CI 1·95–60·72]; p=0·96). The event rate of all intracerebral haemorrhage was 5·00 (95% CI 2·68–8·39) per 100 patient-years in the DOAC group versus 0·82 (0·14–2·53) per 100 patient years in the no anticoagulant group. Serious adverse events occurred in 70 (44%) of 158 patients in the DOAC group and 89 (55%) of 161 patients in the no a
{"title":"Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial","authors":"Roland Veltkamp, Eleni Korompoki, Kirsten H Harvey, Emily R Harvey, Cornelia Fießler, Uwe Malzahn, Viktoria Rücker, Joan Montaner, Valeria Caso, Igor Sibon, Peter Ringleb, Omid Halse, Klemens Hügen, Sabine Ullmann, Carolin Schuhmann, Gabriele Putz Todd, Kirsten Haas, Elena Palà, Stéphanie Debette, Morgane Lachaize, Robyn Lotto","doi":"10.1016/s0140-6736(25)00333-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00333-2","url":null,"abstract":"<h3>Background</h3>Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage.<h3>Methods</h3>PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03996772</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is complete.<h3>Findings</h3>Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p<0·0001). The rate of all ischaemic stroke events was 0·83 (95% CI 0·14–2·57) per 100 patient-years in the DOAC group versus 8·60 (5·43–12·80) per 100 patient-years in the no anticoagulant group. For first recurrent intracerebral haemorrhage, the DOAC group did not meet the prespecified HR for the non-inferiority margin of less than 1·735 (HR 10·89 [90% CI 1·95–60·72]; p=0·96). The event rate of all intracerebral haemorrhage was 5·00 (95% CI 2·68–8·39) per 100 patient-years in the DOAC group versus 0·82 (0·14–2·53) per 100 patient years in the no anticoagulant group. Serious adverse events occurred in 70 (44%) of 158 patients in the DOAC group and 89 (55%) of 161 patients in the no a","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/s0140-6736(25)00335-6
Alimuddin Zumla, Suvanand Sahu, Dorothy Yeboah-Manu, Delia Goletti, Peter S Nyasulu, Sayoki Mfinanga, Mary Shilalukey-Ngoma, Francine Ntoumi, Alfonso J Rodriguez-Morales, Dean B Everett, Adeeba Kamarulzaman, David S Hui
No Abstract
{"title":"Breaking dependency: strengthening the global tuberculosis response in the face of USAID cuts","authors":"Alimuddin Zumla, Suvanand Sahu, Dorothy Yeboah-Manu, Delia Goletti, Peter S Nyasulu, Sayoki Mfinanga, Mary Shilalukey-Ngoma, Francine Ntoumi, Alfonso J Rodriguez-Morales, Dean B Everett, Adeeba Kamarulzaman, David S Hui","doi":"10.1016/s0140-6736(25)00335-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00335-6","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/s0140-6736(25)00334-4
Marie Hatem, Adélaïde Blavier, Susanne Alldén, Jennifer Foucart, Bérangère Taxil, Laura E Keyser, Anne Weyembergh, Olivier Vandenberg
No Abstract
{"title":"Unjustified silence in the face of this new war in eastern DR Congo","authors":"Marie Hatem, Adélaïde Blavier, Susanne Alldén, Jennifer Foucart, Bérangère Taxil, Laura E Keyser, Anne Weyembergh, Olivier Vandenberg","doi":"10.1016/s0140-6736(25)00334-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00334-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"USAID programme suspension in Nigeria: a looming health crisis","authors":"Mubarak Jolayemi Mustapha, Victor Ayooluwa Adeloye, Fatihi Bamigbola Mustapha, Kehinde Alare","doi":"10.1016/s0140-6736(25)00322-8","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00322-8","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"210 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We all provided care for the patient and managed the case. We all reviewed and wrote the article. Written consent for publication was obtained from the patient.
Declaration of interests
MR declares a personal relationship with a senior editor at The Lancet. All remaining authors declare no conflicts of interest.
{"title":"Feeding dystonia, chorea, psychosis, and self-mutilation in an African patient with neuroacanthocytosis syndrome","authors":"Maouly Fall, Moussa Seck, Alassane Mamadou Diop, Jamil Kahwagi, Grace Tsemo Yimta, Allé Guéye, Pedro Rodriguez Cruz, Mie Rizig","doi":"10.1016/s0140-6736(25)00395-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00395-2","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Contributors</h2>We all provided care for the patient and managed the case. We all reviewed and wrote the article. Written consent for publication was obtained from the patient.</section></section><section><section><h2>Declaration of interests</h2>MR declares a personal relationship with a senior editor at <em>The Lancet</em>. All remaining authors declare no conflicts of interest.</section></section>","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/s0140-6736(25)00396-4
No Abstract
{"title":"Retraction and republication—Feeding dystonia, chorea, psychosis, and self-mutilation in an African patient with neuroacanthocytosis syndrome","authors":"","doi":"10.1016/s0140-6736(25)00396-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00396-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/s0140-6736(24)02617-5
John M Dennis, Katherine G Young, Pedro Cardoso, Laura M Güdemann, Andrew P McGovern, Andrew Farmer, Rury R Holman, Naveed Sattar, Trevelyan J McKinley, Ewan R Pearson, Angus G Jones, Beverley M Shields, Andrew T Hattersley
<h3>Background</h3>Data to support individualised choice of optimal glucose-lowering therapy are scarce for people with type 2 diabetes. We aimed to establish whether routinely available clinical features can be used to predict the relative glycaemic effectiveness of five glucose-lowering drug classes.<h3>Methods</h3>We developed and validated a five-drug class model to predict the relative glycaemic effectiveness, in terms of absolute 12-month glycated haemoglobin (HbA<sub>1c</sub>), for initiating dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium–glucose co-transporter-2 inhibitors, sulfonylureas, and thiazolidinediones. The model used nine routinely available clinical features of people with type 2 diabetes at drug initiation as predictive factors (age, duration of diabetes, sex, and baseline HbA<sub>1c</sub>, BMI, estimated glomerular filtration rate, HDL cholesterol, total cholesterol, and alanine aminotransferase). The model was developed and validated with observational data from England (Clinical Practice Research Datalink [CPRD] Aurum), in people with type 2 diabetes aged 18–79 years initiating one of the five drug classes between Jan 1, 2004, and Oct 14, 2020, with holdback validation according to geographical region and calendar period. The model was further validated in individual-level data from three published randomised drug trials in type 2 diabetes (TriMaster three-drug crossover trial and two parallel-arm trials [<span><span>NCT00622284</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> and <span><span>NCT01167881</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>]). For validation in CPRD, we assessed differences in observed glycaemic effectiveness between matched (1:1) concordant and discordant groups receiving therapy that was either concordant or discordant with model-predicted optimal therapy, with optimal therapy defined as the drug class with the highest predicted glycaemic effectiveness (ie, lowest predicted 12-month HbA<sub>1c</sub>). Further validation involved pairwise drug class comparisons in all datasets. We also evaluated associations with long-term outcomes in model-concordant and model-discordant groups in CPRD, assessing 5-year risks of glycaemic failure (confirmed HbA<sub>1c</sub> ≥69 mmol/mol), all-cause mortality, major adverse cardiovascular events or heart failure (MACE-HF) outcomes, renal progression, and microvascular complications using Cox proportional hazards regression adjusting for relevant demographic and clinical covariates.<h3>Findings</h3>The five-drug class model was developed from 100 107 drug initiations in CPRD. In the overall CPRD cohort (c
{"title":"A five-drug class model using routinely available clinical features to optimise prescribing in type 2 diabetes: a prediction model development and validation study","authors":"John M Dennis, Katherine G Young, Pedro Cardoso, Laura M Güdemann, Andrew P McGovern, Andrew Farmer, Rury R Holman, Naveed Sattar, Trevelyan J McKinley, Ewan R Pearson, Angus G Jones, Beverley M Shields, Andrew T Hattersley","doi":"10.1016/s0140-6736(24)02617-5","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02617-5","url":null,"abstract":"<h3>Background</h3>Data to support individualised choice of optimal glucose-lowering therapy are scarce for people with type 2 diabetes. We aimed to establish whether routinely available clinical features can be used to predict the relative glycaemic effectiveness of five glucose-lowering drug classes.<h3>Methods</h3>We developed and validated a five-drug class model to predict the relative glycaemic effectiveness, in terms of absolute 12-month glycated haemoglobin (HbA<sub>1c</sub>), for initiating dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium–glucose co-transporter-2 inhibitors, sulfonylureas, and thiazolidinediones. The model used nine routinely available clinical features of people with type 2 diabetes at drug initiation as predictive factors (age, duration of diabetes, sex, and baseline HbA<sub>1c</sub>, BMI, estimated glomerular filtration rate, HDL cholesterol, total cholesterol, and alanine aminotransferase). The model was developed and validated with observational data from England (Clinical Practice Research Datalink [CPRD] Aurum), in people with type 2 diabetes aged 18–79 years initiating one of the five drug classes between Jan 1, 2004, and Oct 14, 2020, with holdback validation according to geographical region and calendar period. The model was further validated in individual-level data from three published randomised drug trials in type 2 diabetes (TriMaster three-drug crossover trial and two parallel-arm trials [<span><span>NCT00622284</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> and <span><span>NCT01167881</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>]). For validation in CPRD, we assessed differences in observed glycaemic effectiveness between matched (1:1) concordant and discordant groups receiving therapy that was either concordant or discordant with model-predicted optimal therapy, with optimal therapy defined as the drug class with the highest predicted glycaemic effectiveness (ie, lowest predicted 12-month HbA<sub>1c</sub>). Further validation involved pairwise drug class comparisons in all datasets. We also evaluated associations with long-term outcomes in model-concordant and model-discordant groups in CPRD, assessing 5-year risks of glycaemic failure (confirmed HbA<sub>1c</sub> ≥69 mmol/mol), all-cause mortality, major adverse cardiovascular events or heart failure (MACE-HF) outcomes, renal progression, and microvascular complications using Cox proportional hazards regression adjusting for relevant demographic and clinical covariates.<h3>Findings</h3>The five-drug class model was developed from 100 107 drug initiations in CPRD. In the overall CPRD cohort (c","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：