Discontinuation of antihypertensive and lipid-lowering medication in primary care: a systematic review of observational data

BackgroundCardiovascular disease (CVD) risk is managed in primary care using lipid-lowering therapies (LLTs) and antihypertensives (AHTs) for primary (no prior CVD) or secondary (with prior CVD) prevention, but patients may discontinue treatment. Little synthesised real-world data for LLT/AHT discontinuation exists. MethodsWe systematically reviewed English language reports of observational studies from PubMed, EMBASE, Web of Science, and CINAHL published from 2010-2025 describing discontinuation/restarting prevalence for first-to-third line LLTs/AHTs used for CVD prevention in primary care (PROSPERO: CRD420250599340). Data were extracted on discontinuation/restarting prevalences and associations between discontinuation and sociodemographic factors. FindingsOf 5,756 records, 31 (16 LLT; 15 AHT) reports were included representing 9,146,252 patients. Risk of bias was generally low except for two papers with substantial risk of bias from unmeasured confounding. LLT median (IQR) discontinuation and restarting prevalences were 43% (38%; 54%) and 43% (22%; 64%), respectively. AHT discontinuation and restarting prevalences were 41% (30%; 49%) and 28%, respectively. Discontinuation/restarting prevalence depended on discontinuation definition and indication. Patients aged around 65 years old were less likely to discontinue than younger or older patients, for both LLTs and AHTs. Women discontinued LLTs more often irrespective of indication; men discontinued AHTs more often for primary prevention. Income-based socioeconomic position (SEP) measures were associated with discontinuation, but composite SEP measures were not. Minority ethnic groups were more likely to discontinue LLTs and AHTs. InterpretationThis systematic review of real-world data identified discontinuation inequities in first-to-third line LLTs and AHTs based on age, sex, and ethnicity. Awareness of these patterns and additional research into patient-level drivers of drug discontinuation could improve health equity by addressing LLT/AHT discontinuation in the highest-risk patients. FundingThis work was funded by the NIHR UCLH BRC. No funders had any role in data collection, analysis, manuscript preparation, or the decision to publish. Research in contextWe searched PubMed for reviews, systematic reviews, and meta-analyses examining associations between age, sex, socioeconomic position, ethnicity (search string: "sociodemograph*" OR "age" OR "sex" OR "socioeconomic status" OR "socioeconomic position" OR "ethnic*" OR "race" OR "racial" OR "Asian*" OR "India*" OR "Pakistan*" OR "Bangladesh*" OR "Black" OR "African" OR "Afro*") and discontinuation (search string: persist* or discontinu* or stop*) of antihypertensives/lipid-lowering drugs (search string: "anti$hypertensive" OR "blood*pressure lowering" OR "ACE inhibitor" OR "angiotensin receptor blocker" OR "calcium channel blocker" OR "thiazide-like diuretic" OR "thiazide diuretic" OR "lipid*lowering" OR "lipid*reducing" OR "statin" OR "HMG-CoA reductase inhibitors" OR "proprotein convertase subtilisin/kexin type 9" OR "PCSK9 inhibitor"). We did not restrict reports by date or language. Of 711 results, one relevant article was found. Two more relevant articles were found in the searches performed for this systematic review. One 2017 systematic review of twenty-two real-world studies found that for nineteen studies with a dichotomous discontinuation outcome, 16% to 93% of patients discontinued statins across follow-up time of 0 days (cross-sectional studies) to median 4.1 years follow-up. The authors did not report on the proportion of patients discontinuing by sociodemographic group. A 2018 systematic review and meta-analysis of RCTs and real-world data found that for patients aged [≥]65, lower income was associated with discontinuation across seven studies (odds ratio [95% confidence interval] 1{middle dot}20 [1{middle dot}06 to 1{middle dot}36]), though the degree of heterogeneity in the studies used for meta-analysis was high (I2 = 0.89). Female gender (1{middle dot}03 [0{middle dot}98 to 1{middle dot}09]) was not associated with statin discontinuation, and there was a trend towards an association between Black/non-White race and discontinuation (1{middle dot}57 [0{middle dot}92-2.68]). A 2024 systematic review of 52 RCTs and real-world studies found that the prevalence of statin discontinuation ranged from 0.8% to 70.5%, and was higher for primary prevention, and that male sex and non-White ethnicity were associated with statin discontinuation. Our search found no prior systematic reviews or meta-analyses describing differences in discontinuation of AHTs by age, sex, SEP or ethnicity. Added value of this studyThis study is the first systematic review of sociodemographic factors influencing antihypertensive discontinuation in primary care, and complements the findings described above with new evidence on statin discontinuation in real-world settings. With respect to statins and/or ezetimibe, we found that younger (below 60) and older (above 75) patients were more likely to discontinue statins, for both primary and secondary prevention. Female sex was associated with a small but consistent increase in statin discontinuation across our included studies. Individual income appeared to associate with statin discontinuation, but not composite SEP measures such as the Indices of Multiple Deprivation. For antihypertensives, we found that younger and older patients were more likely to discontinue for both primary and secondary prevention, with discontinuation at its lowest around 70 years. Male sex was associated with a small but consistent increase in discontinuation in primary prevention but was associated with marginally reduced discontinuation in a larger study of patients using AHTs for mixed prevention. Lower individual income appeared to positively associate with antihypertensive discontinuation, but composite SEP measures did not. In all studies reporting ethnic differences in discontinuation, non-majority ethnic groups were consistently more prone to discontinuation. Implications of all the available evidenceNon-persistence rates for lipid-lowering medications and antihypertensives are considerable and constitute a possible avenue to reduce CVD. In the first comprehensive evidence synthesis across socio-demographic groups, we show discontinuation rates in real-world settings differ across groups, which may contribute to existing health inequities. For statins, it is unclear how sex associates with discontinuation, given the inconsistency of results across different systematic reviews and meta-analyses. Low income and minority ethnic group membership are associated with statin discontinuation. Our findings suggest that commonly used AHTs are discontinued more often in men than in women, in the youngest and oldest patients, and in minority ethnic groups. Lower individual income may associate with statin discontinuation, but belonging to a lower SEP group such those derived from the Indices of Multiple Deprivation was not associated with statin discontinuation. Future research efforts should address the intersectionality in these patterns, to ascertain whether sociodemographic disadvantages combine to drive higher discontinuation rates in specific patient subgroups. Data on discontinuation by the type of LLT/AHT used (e.g. angiotensin-converting enzyme inhibitor versus for AHTs) should also be collated. Causes for antihypertensive/lipid-lowering medication discontinuation should be investigated using qualitative methods to ascertain reasons for discontinuation in patient groups directly, utilising underrepresented patient populations where possible. Data from such qualitative studies may inform future interventions to reduce discontinuation in the most at-risk patient groups. Clinicians should heighten efforts to maintain or reinitiate therapy in those prone to lipid-lowering therapy and antihypertensive discontinuation, assuming no clinical contraindications.