Cardiovascular outcomes and fracture risk after the discontinuation of preventative medications in older patients with complex health needs: a self-controlled case series analysis

Objective To assess the effect of stopping statins, antihypertensives, and bisphosphonates on the risk of cardiovascular events and fractures in older patients with complex health needs (CHN). Methods Patients aged >65 years, registered in CPRD GOLD for ≥1 year before study start (01/01/2010) and with CHN (non-elective hospitalisation/s, frailty or polypharmacy) were selected. Self-controlled case series (SCCS) analyses were subsequently conducted among people who did not use the respective preventative treatment in the year before study start. Incidence rate ratios (IRR) were calculated for myocardial infarction (MI) and stroke [antihypertensives, statins] and fractures [bisphosphonates] comparing event rates for the respective outcomes during treatment vs. post-discontinuation periods. Results 198,039 people were included to the CHN cohort. Among those, 6,245 individuals were included for the analysis of bisphosphonate discontinuation and fracture risk; 738 and 669 persons for the analysis of antihypertensive therapy discontinuation and MI/stroke risk; and 1,408 and 1,361 people for statin discontinuation and MI/stroke risk. Risk of MI was substantially increased following discontinuation of antihypertensives (IRR 2.6 [95%CI 1.56-4.33]) and statins (IRR 1.75 [1.16-2.62]). No significant association for treatment discontinuation and stroke risk was seen. Likewise, no increased fracture risk was seen after discontinuing bisphosphonates. However, discontinuation among people with >1 year history of bisphosphonate therapy pointed towards increased fracture risk. Conclusions Our study showed risks associated with discontinuing preventative medications in people with CHN, likely explained by the continued efficacy of these medications. Further research focussing on the risk-benefit of these treatments for most vulnerable older adults is needed. ### Competing Interest Statement DPA 's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department. All other authors declare no conflict. ### Funding Statement The project was supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC). DPA is funded through a NIHR Senior Research Fellowship (Grant number SRF-2018-11-ST2-004). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Independent Scientific Advisory Committee for the Clinical Practice Research Datalink, including amendments (Protocol No 19_132A2). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data were obtained from CPRD under the Oxford University CPRD license. Direct data sharing is not allowed. Data access can be obtained from CPRD, conditional on approval through CPRD s Research Data Governance Process.