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Background: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality., Methods: This randomised controlled trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3 years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221)., Findings: Between March 20, 2017, and Sept 30, 2018, a total of 569 participants were randomly assigned. Of these, 564 (99%; intervention=280; control=284) were followed up for a median of 4·0 years (IQR 3·7-4·3). Participants had a mean age of 84·8 years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109 participants at follow-up (51% of the 213 participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference -0·35 drugs [95% CI -0·52 to -0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76 to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64 to 1·00])., Interpretation: Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives., Funding: British Heart Foundation and National Institute for Health and Care Research., Competing Interests: Declaration of interests JPS reports funding from the Wellcome Trust/Royal Society, National Institute for Health and Care Research (NIHR), British Heart Foundation, and Stroke Association; payment for consultancy from DoctorLink; is a Data Safety Monitoring Board member for the Hypertension Treatment in Nigeria Study sponsored by Northwestern University; and is Secretary and trustee for the British and Irish Hypertension Society. GAF is Board non-executive Director for the National Institute for Health and Care Excellence. FDRH reports honoraria for lectures from Pfizer/BMS, Bayer, Boehringer Ingelheim, and AstraZeneca; and is chair of the European Primary Care Cardiovascular Society and International Primary Care Cardiovascular Society. SdL has received research grants to his university for investigator-led cardiometabolic research from Bristol Myers Squibb, Eli Lilly, GSK, MSD, Novo Nordisk, Pfizer, Sanofi, and Seqirus; has been a member of advisory boards for AstraZeneca, GSK, Sanofi, and Seqirus; and has received medical writing support provided by AstraZeneca, GSK, and Pfizer. JM reports funding from an NIHR Senior Investigator Award and honoraria for lectures from Bristol Myers Squibb and Pfizer. RAP reports NIHR funding to his institution for other research related to medicines use and Medical Research Council funding to his institution unrelated to this project. L-MY reports NIHR funding to her institution for other research. RJM reports funding from the NIHR, British Heart Foundation, and Stroke Association; has received royalties, consulting fees (paid to his institution), and research equipment from Omron; has received royalties from Sensyne; and has received honoraria (paid to his institution) for lectures from the Finnish Hypertension Society and Canadian Hypertension Society., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Dupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease., Methods: In this phase 2b, randomised, double-blind, placebo-controlled trial adults with early-stage Dupuytren's disease and an established clinically distinct nodule with a clear history of progression in the preceding 6 months were recruited from two clinical centres in the UK and were randomly assigned 1:1 to receive four injections of adalimumab or saline every 3 months. Participants and assessors were masked. The primary outcome was nodule hardness measured with a durometer at 12 months. Data were analysed by linear mixed effects regression models in the intention-to-treat population with multiple imputation for missing primary outcome data. The trial is registered at the ISRCTN registry, ISRCTN 27786905 and is complete., Findings: Between Feb 17, 2017, and Jan 11, 2019, 284 participants were screened in the UK and 140 were enrolled. 47 (34%) participants were female and 93 (66%) were male. Mean age of participants was 59·7 years (SD 10·0). Primary outcome data were available from 113 participants. Nodule hardness was lower (-4·6 AU [95% CI -7·1 to -2·2], p=0·0002) in the adalimumab compared with the saline group at 12 months. There were no related serious adverse events; the most common adverse events were minor injection site reactions., Interpretation: Intranodular injections of adalimumab in participants with early-stage Dupuytren's disease resulted in softening and reduction in size of the nodules. Longer follow-up would be required to assess the effect of tumour necrosis factor inhibition on disease progression, extension deficit and hand function., Competing Interests: Declaration of interests JN receives consulting fees and has received research grants from 180 Life Sciences Corp (180LS). MF has been executive co-chairman of 180LS since November 2020 and receives payment for this. JN and MF hold stock in 180LS, which has exclusively licensed intellectual property for the treatment of Dupuytren’s disease from the University of Oxford. SEL was appointed as a member of the Scientific Advisory Board of 180LS in Feb, 2022, and has not received any payments. The other authors declare no competing interests.