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Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

[This corrects the article DOI: 10.1371/journal.pmed.1004223.].

The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

Background Neuropathic pain significantly reduces an individual’s quality of life and places a significant economic burden on society. As such, many cost-effectiveness analyses (CEAs) have been published for treatments available for neuropathic pain. Objectives The primary objective of this systematic review was to provide a detailed summary of the estimates of cost-effectiveness from published CEAs comparing available treatments for neuropathic pain. The secondary objectives were to identify the key drivers of cost-effectiveness and to assess the quality of published CEAs in neuropathic pain. Methods We searched Embase, MEDLINE, Cochrane CENTRAL and seven other databases to identify CEAs reporting the costs, health benefits (e.g., quality-adjusted life-years or disability-adjusted life-years) and summary statistics, such as incremental cost-effectiveness ratios, of treatments for neuropathic pain. We excluded studies reporting diseases other than neuropathic pain, those for which the full text was not available (e.g., conference abstracts), studies not written in English or not published in peer-reviewed journals, and narrative reviews, editorials and opinion papers. Titles and abstract reviews, full-text reviews, and data extraction were all performed by two independent reviewers, with disagreement resolved by a third reviewer. Mean costs, health benefits, and summary statistics were reported and qualitatively compared across studies, stratified by time horizon. Drivers of cost-effectiveness were assessed using reported one-way sensitivity analyses. The quality of all included studies was evaluated using the Tufts CEA Registry Quality Score and study reporting using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist. Results A total of 22 studies were identified and included in this systematic review. Included studies were heterogeneous in the treatments compared, methodology and design, perspectives, and time horizons considered, making cross-study comparisons difficult. No single treatment was consistently the most cost-effective across all studies, but tricyclic antidepressants were the preferred treatment at a willingness-to-pay threshold of $US50,000 per quality-adjusted life-year in several studies with a short time horizon and a US payer perspective. Among the 14 studies reporting one-way sensitivity analyses, drivers of cost-effectiveness included utility values for health states and the likelihood of pain relief with treatment. The quality of the identified CEAs was moderate to high, and overall reporting largely met CHEERS recommendations. Limitations To assess drivers of cost-effectiveness and quality, we only included studies with the full text available and thus excluded some CEAs that reported cost-effectiveness results. The heterogeneity of the included studies meant that the study results could not be synthesized and comparison across studies was limited. Conclusions Though many pulished studies have evaluated the cost-effectiveness of treatments for neuropathic pain, significant heterogeneity between CEAs prevented synthesis of the results. Standardized methodology and improved reporting would allow for more reliable comparisons across studies.

Statin medications reduce the risk of atherosclerotic cardiovascular disease (ASCVD). China's new central government medicine procurement policy lowered statin prices by five-fold or more, which may impact the cost-effectiveness of statin therapy. To explore the impact of China's 2019 centralized medicine procurement policy on the cost-effectiveness of statins treatment for primary ASCVD prevention. A microsimulation decision tree analytic model was built using individual participant data from ASCVD-free adults aged 35-64 years (n = 21,265) in the China Multi-provincial Cohort Study. ASCVD incidence, costs (2019 Int$), and quality-adjusted life years (QALYs) over a 10-year period from health-care sector and societal perspectives were estimated. Effect and cost-effectiveness of low-dose statins (equivalent potency regimens of simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day) and moderate-dose (double low dose) statins therapy were simulated. The incremental cost-effectiveness ratio (ICER) of statin treatment was compared with no treatment by category of 10-year ASCVD risk. New lower prices of statins were from the centralized procurement policy bid-winning announcement file. One-way and probabilistic sensitivity analyses quantified model uncertainty. Low-dose statins interventions reduced 10-year ASCVD incidence by 4.1%, 9.7%, and 15.5% among people with low, moderate, and high risk comparing to no treatment. Lowering statin prices to the 2019 central government procurement policy level could lower the ICER of low-dose statins treatment for high-risk people from Int$ 141,000 to Int$ 51,300 per QALY gained from health-care sector perspective. Moderate-dose statin treatment lowered the ICER compared with the low-dose statins treatment in each ASCVD risk category (Int$ 43,100 vs. Int$ 51,300 per QALY gained from the health-care sector perspective for high risk people). Cost-effectiveness improved progressively with increased baseline ASCVD risk. Implementing low central government prices will substantially improve the cost-effectiveness of statins for primary ASCVD prevention in 35-64-year-old Chinese adults.

In a cost-effectiveness analysis, intensive blood-pressure control rather than standard treatment (target, <120 mm Hg vs. <140 mm Hg) was associated with an incremental cost-effectiveness ratio of about $47,000 per quality-adjusted life-year gained.

Hypertension guidelines recommend initiating treatment with single pill combination (SPC) antihypertensive medications, but SPCs are used by only one-third of treated hypertensive US adults. This analysis estimated the cost-effectiveness of initial treatment with SPC dual antihypertensive medications compared with usual care monotherapy in hypertensive US adults.The validated BP Control Model-Cardiovascular Disease (CVD) Policy Model simulated initial SPC dual therapy (two half-standard doses in a single pill) compared with initial usual care monotherapy (half-standard dose when baseline systolic BP < 20 mmHg above goal and one standard dose when ≥20 mmHg above goal). Secondary analyses examined equivalent dose monotherapy (one standard dose) and equivalent dose dual therapy as separate pills (two half-standard doses). The primary outcomes were direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) over 10 years from a US healthcare sector perspective.At 10 years, initial dual drug SPC was projected to yield 0.028 (95%UI 0.008 to 0.051) more QALYs at no greater cost ( $73, 95%UI -$ 1 983 to$1 629) than usual care monotherapy. In secondary analysis, SPC dual therapy was cost-effective vs. equivalent dose monotherapy (ICER $ 8 000/QALY gained) and equivalent dose dual therapy as separate pills (ICER $57 000/QALY gained). At average drug prices, initiating antihypertensive treatment with SPC dual therapy is more effective at no greater cost than usual care initial monotherapy and has the potential to improve BP control rates and reduce the burden of CVD in the US.

Home blood pressure monitoring with clinical or technological support (Supported HBPM) is an evidence-based intervention recommended by national guidelines for improving hypertension (HTN) control. However, few healthcare systems have implemented Supported HBPM because it remains unclear how best to promote uptake among patients and clinicians, and the real-world effectiveness of Supported HBPM is unknown. The Monitor-BP Trial aims to determine the impact of implementing a flexible Supported HBPM program on practice-level HTN control and to evaluate the reach, adoption, maintenance, and cost-effectiveness of the program in a socioeconomically diverse primary care network. The Monitor-BP Trial takes place in 15 primary care practices affiliated with two large academic medical centers in New York City. It is a hybrid 2 effectiveness-implementation cluster randomized pre-post trial testing early implementation of a Supported HBPM program (8 practices) versus usual care (7 practices). Adult patients with diagnosed HTN and their primary care clinicians are eligible for inclusion. The intervention consists of two program options: (1) MyCare Hypertension, a low resource intensity option in which patients use their own BP devices to track home BP in the online patient portal with automated triage support for extreme readings and portal-delivered educational modules, (2) RPM Hypertension, a high resource intensity option in which patients are loaned wireless BP devices that automatically transmit home BP data to the electronic health record (EHR) with telehealth navigator onboarding and nursing support to triage extreme readings. Both options include EHR-integrated ordering and home BP data visualization for clinicians. Key features of the implementation strategy include clinician education and training via presentations, clinician prompts and reminders via e-mails and mailed postcards, detailed instructional materials for patients and clinicians via websites, and at least monthly problem-solving meetings with clinical champions to iteratively tailor implementation to individual practices. The primary effectiveness outcome is practice-level pre- to post-implementation change in the mean 12-month change in office systolic BP among patients with uncontrolled office BP at baseline. The primary implementation outcomes are reach (uptake of the Supported HBPM program by patients) and adoption (uptake of the Supported HBPM program by clinicians). Secondary outcomes include estimating the short- and long-term cost-effectiveness of the program. The Monitor-BP Trial tests a scalable approach to implementing telemonitoring-enabled Supported HBPM interventions into real-world clinical settings. Our findings have the potential to inform how health systems can shift the paradigm of BP assessments from the office to the home.

Heart failure with reduced ejection fraction produces substantial morbidity, mortality, and health care costs. Dapagliflozin is the first sodium-glucose cotransporter 2 inhibitor approved for the treatment of heart failure with reduced ejection fraction. To examine the cost-effectiveness of adding dapagliflozin to guideline-directed medical therapy for heart failure with reduced ejection fraction in patients with or without diabetes. This economic evaluation developed and used a Markov cohort model that compared dapagliflozin and guideline-directed medical therapy with guideline-directed medical therapy alone in a hypothetical cohort of US adults with similar clinical characteristics as participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial. Dapagliflozin was assumed to cost $4192 annually. Nonparametric modeling was used to estimate long-term survival. Deterministic and probabilistic sensitivity analyses examined the impact of parameter uncertainty. Data were analyzed between September 2019 and January 2021. Lifetime incremental cost-effectiveness ratio in 2020 US dollars per quality-adjusted life-year (QALY) gained. The simulated cohort had a starting age of 66 years, and 41.8% had diabetes at baseline. Median (interquartile range) survival in the guideline-directed medical therapy arm was 6.8 (3.5-11.3) years. Dapagliflozin was projected to add 0.63 (95% uncertainty interval [UI], 0.25-1.15) QALYs at an incremental lifetime cost of $42 800 (95% UI, $37 100-$50 300), for an incremental cost-effectiveness ratio of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained; cost-effective in 94% of probabilistic simulations at a threshold of $100 000 per QALY gained). Findings were similar in individuals with or without diabetes but were sensitive to drug cost. In this study, adding dapagliflozin to guideline-directed medical therapy was projected to improve long-term clinical outcomes in patients with heart failure with reduced ejection fraction and be cost-effective at current US prices. Scalable strategies for improving uptake of dapagliflozin may improve long-term outcomes in patients with heart failure with reduced ejection fraction.