Cost-effectiveness of Mediterranean diet and physical activity in secondary CVD prevention: results from the UCC-SMART cohort study.

AIMS: The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess if they are also cost-effective in patients with established CVD. METHODS: A cost-utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in CVD patients. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100,000 CVD patients sampled from the UCC-SMART study (N = 8,947, mean age 62 ±8.7 years and 74% male). Cost-effectiveness was expressed as incrementalcost-effectiveness ratio (ICER), incremental net health benefit (INHB) and incremental net monetary benefit (INMB). RESULTS: Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of €1,236 per person compared to usual care, resulting in an ICER of €-626/QALY (95%CI -1,929 to 2,673). At a willingness-to-pay of €20,000/QALY, INHB was 2.04 (95%CI 0.99-3.58) QALY and INMB was €40,757 (95%CI 19,819-71,605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs. CONCLUSION: In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared to usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all CVD patients.

Lifestyle optimization, including physical activity and healthy diet, is a central recommendation for preventing recurrent cardiovascular events. In this study, we assessed if improving physical activity habits and adherence to a heart-healthy Mediterranean diet would also be a cost-effective option. The results were remarkable - following the Mediterranean diet and engaging in physical activity was expected to result in an increase of 2.0 quality-adjusted life years (QALYs, equal to a life year in perfect health) and cost savings. This means that lifestyle optimization in secondary CVD prevention improves population health, while reducing overall health care costs. These findings underscore the importance of implementing lifestyle changes in the care for all individuals with CVD. A health lifestyle is not only effective in improving health but also a prudent financial decision. Key messages  A combined Mediterranean diet and physical activity intervention is expected to result in two additional QALYs and three additional life years free of recurrent cardiovascular events per patient with with established CVDTargeting a healthy lifestyle is expected to lead to costs savings compared to usual care, due to the low costs of the intervention and the high efficacy in preventing recurrent cardiovascular events.Lifestyle optimization in secondary CVD prevention was shown to result in a dominant incremental cost-effectiveness ratio (ICER) of €-626/QALY, which strongly advocates for healthy policy targeted at implementing lifestyle interventions in regular care for CVD patients.

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

The readiness of public primary health care (PUSKESMAS) for cardiovascular services in Makasar city, Indonesia.

BACKGROUNDS: The increasing burden of cardiovascular disease (CVD) has become a major challenge globally, including in Indonesia. Understanding the readiness of primary health care facilities is necessary to confront the challenge of providing access to quality CVD health care services. Our study aimed to provide information regarding readiness to deliver CVD health services in public primary health care namely Puskesmas. METHODS: The study questionnaire was adapted from the World Health Organization (WHO) Service Availability and Readiness Assessment (SARA), modified based on the package of essentials for non-communicable disease (PEN) and the Indonesian Ministry of health regulation. Data were collected from all Puskesmas facilities (N = 47) located in Makassar city. We analysed relevant data following the WHO-SARA manual to assess the readiness of Puskesmas to deliver CVD services. Human resources, diagnostic capacity, supporting equipment, essential medication, infrastructure and guidelines, and ambulatory services domain were assessed based on the availability of each tracer item in a particular domain. The mean domain score was calculated based on the availability of tracer items within each domain. Furthermore, the means of all domains' scores are expressed as an overall readiness index. Higher scores indicate greater readiness of Puskesmas to deliver CVD-related health care. RESULTS: Puskesmas delivers health promotion, disease prevention, and prompt diagnosis for cardiovascular-related diseases, including hypertension, diabetes, coronary heart disease (CHD), and stroke. Meanwhile, basic treatments were observed in the majority of the Puskesmas. Long-term care for hypertension and diabetes patients and rehabilitation for CHD and stroke were only observed in a few Puskesmas. The readiness score of Puskesmas to deliver CVD health care ranged from 60 to 86 for. Furthermore, there were 11 Puskesmas (23.4%) with a score below 75, indicating a sub-optimal readiness for delivering CVD health services. A shortage of essential medicines and a low capacity for diagnostic testing were the most noticeable shortcomings leading to suboptimal readiness for high-quality CVD health services. CONCLUSION: Close cooperation with the government and other related stakeholders is required to tackle the identified shortcomings, especially the continuous monitoring of adequate supplies of medicines and diagnostic tools to achieve better CVD care for patients in Indonesia.

Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Plasma Trough Concentrations of Antihypertensive Drugs for the Assessment of Treatment Adherence: A Meta-Analysis.

Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan. PubMed was searched for pharmacokinetic studies up to September 2020. Eligible studies reported steady-state mean trough concentration and their variance. Pooled trough concentrations were estimated using a three-level random effects meta-analytic model. Moderator analyses were performed to explore sources of heterogeneity. One thousand three hundred eighteen potentially relevant articles were identified of which 45 were eligible for inclusion. The pooled mean trough concentration was 9.2 ng/mL (95% CI, 7.5-10.8) for amlodipine, 41.0 ng/mL (95% CI, 17.4-64.7) for hydrochlorothiazide, and 352.9 ng/mL (95% CI, 243.5-462.3) for valsartan. Substantial heterogeneity was present for all 3 pooled estimates. Moderator analyses identified dosage as a significant moderator for the pooled trough concentration of amlodipine (ß1=0.9; P<0.05), mean age, and mean body weight for the mean trough concentration of hydrochlorothiazide (ß1=2.2, P<0.05, respectively, ß1=-4.0, P<0.05) and no significant moderators for valsartan. Plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan, measured with liquid chromatography-tandem mass spectrometry, are highly heterogeneous over the different studies. Use of the pooled trough concentration as a cutoff in the biochemical assessment of adherence can result in inaccurate diagnosis of (non-)adherence, which may seriously harm the patient-physician relationship, and is therefore not recommended.

Would treatment decisions about secondary prevention of CVD based on estimated lifetime benefit rather than 10-year risk reduction be cost-effective?

OBJECTIVE: To test the hypothesis that treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years. METHODS: A microsimulation model was constructed for 10,000 patients with stable cardiovascular disease (CVD). Costs and quality-adjusted life years (QALYs) due to recurrent cardiovascular events and (non)vascular death were estimated for lifetime benefit-based compared to 10-year risk-based treatment, with PCSK9 inhibition as an illustration example. Lifetime benefit in months gained and 10-year absolute risk reduction were estimated using the SMART-REACH model, including an individualized treatment effect of PCSK9 inhibitors based on baseline low-density lipoprotein cholesterol. For the different numbers of patients treated (i.e. the 5%, 10%, and 20% of patients with the highest estimated benefit of both strategies), cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER), indicating additional costs per QALY gain. RESULTS: Lifetime benefit-based treatment of 5%, 10%, and 20% of patients with the highest estimated benefit resulted in an ICER of €36,440/QALY, €39,650/QALY, or €41,426/QALY. Ten-year risk-based treatment decisions of 5%, 10%, and 20% of patients with the highest estimated risk reduction resulted in an ICER of €48,187/QALY, €53,368/QALY, or €52,390/QALY. CONCLUSION: Treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years.

The effect of computerized decision support systems on cardiovascular risk factors: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular risk management (CVRM) is notoriously difficult because of multi-morbidity and the different phenotypes and severities of cardiovascular disease. Computerized decision support systems (CDSS) enable the clinician to integrate the latest scientific evidence and patient information into tailored strategies. The effect on cardiovascular risk factor management is yet to be confirmed. METHODS: We performed a systematic review and meta-analysis evaluating the effects of CDSS on CVRM, defined as the change in absolute values and attainment of treatment goals of systolic blood pressure (SBP), low density lipoprotein cholesterol (LDL-c) and HbA1c. Also, CDSS characteristics related to more effective CVRM were identified. Eligible articles were methodologically appraised using the Cochrane risk of bias tool. We calculated mean differences, relative risks, and if appropriate (I2 < 70%), pooled the results using a random-effects model. RESULTS: Of the 14,335 studies identified, 22 were included. Four studies reported on SBP, 3 on LDL-c, 10 on CVRM in patients with type II diabetes and 5 on guideline adherence. The CDSSs varied considerably in technical performance and content. Heterogeneity of results was such that quantitative pooling was often not appropriate. Among CVRM patients, the results tended towards a beneficial effect of CDSS, but only LDL-c target attainment in diabetes patients reached statistical significance. Prompting, integration into the electronical health record, patient empowerment, and medication support were related to more effective CVRM. CONCLUSION: We did not find a clear clinical benefit from CDSS in cardiovascular risk factor levels and target attainment. Some features of CDSS seem more promising than others. However, the variability in CDSS characteristics and heterogeneity of the results - emphasizing the immaturity of this research area - limit stronger conclusions. Clinical relevance of CDSS in CVRM might additionally be sought in the improvement of shared decision making and patient empowerment.

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

Cost-effectiveness of PCSK9 inhibition in addition to standard lipid-lowering therapy in patients at high risk for vascular disease.

BACKGROUND: As proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibodies are entering the market, we assessed the cost-effectiveness of PCSK9 inhibition added to standard lipid-lowering therapy in patient groups at high risk for major adverse cardiovascular events (MACE). METHODS: A lifetime Markov Model was designed to estimate healthcare costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for PCSK9 inhibition added to standard therapy in patients with Familial Hypercholesterolemia (FH), patients with vascular disease at high MACE recurrence risk, and patients with vascular disease with diabetes mellitus. The balance between costs and health outcomes was established for a broad range of potential relative risk reductions and drug costs. RESULTS: The expected QALY gain per patient and ICER in the main scenario were 1.4 QALYs for €78,485/QALY gained in patients with FH, 0.22 QALYs for €176,735/QALY gained in those with vascular disease and a predicted risk of MACE ≥30% in 10years, and 0.22 QALYs for €295,543/QALY gained in those with vascular disease and diabetes. Results were sensitive to assumptions on PCSK9 inhibitor treatment efficacy, and vascular event risks. CONCLUSION: The costs and effects of PCSK9 inhibition added to standard lipid-lowering treatment in patient groups at high risk for MACE can be estimated and adapted to a specific clinical setting. PCSK9 inhibition could be cost-effective in patients with FH. In patients with vascular disease PCSK9 inhibition is less cost-effective, however, a price development may change clinical practice. This model may aid treatment and reimbursement decisions regarding PCSK9 inhibitors.

Cost-Effectiveness of Intensifying Lipid-Lowering Therapy With Statins Based on Individual Absolute Benefit in Coronary Artery Disease Patients.

BACKGROUND: A validated prediction model estimates the absolute benefit of intensive versus standard lipid-lowering therapy (LLT) with statins on next major cardiovascular events for individual patients with coronary artery disease. We aimed to assess whether targeting intensive LLT therapy to coronary artery disease patients with the highest predicted absolute benefit is cost-effective compared to treating all with standard or all with intensive LLT. METHODS AND RESULTS: A lifetime Markov model was constructed for coronary artery disease patients (n=10 000) with mean age 61 years. Number of major cardiovascular events, (non) vascular death, costs, and quality-adjusted life years (QALYs) were estimated for the following strategies: (1) standard LLT for all (reference strategy); (2) intensive LLT for those with 5-year absolute major cardiovascular events risk reduction (ARR) ≥3%, ≥2.3%, or ≥1.5% (corresponding to ≥20%, ≥15%, or ≥10% 5-year major cardiovascular events risk); and (3) intensive LLT for all. With intensive LLT for those with ≥3% 5-year ARR (13% of patients), 380 QALYs were gained for €2423/QALY. Using a threshold of ≥2.3% ARR (26% of patients), 630 QALYs were gained for €5653/QALY. Using a threshold of ≥1.5% ARR (56% of patients), 1020 QALYs were gained for €10 960/QALY. By treating all intensively, 1410 QALYs were gained (0.14 QALY per patient) for €17 223/QALY. With benefit-based treatment, 0.16 to 0.17 QALY was gained per treated patient. CONCLUSIONS: Intensive LLT with statins for all coronary artery disease patients results in the highest overall QALY gain against acceptable costs. However, the number of QALYs gained with intensive LLT by statins in individual patients can be increased with selective benefit-based treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00327691 and NCT00159835.

[Familial hypercholesterolemia: why screening, counselling and treatment should be integrated]. / Familiaire hypercholesterolemie: waarom opsporing en behandeling bij elkaar horen.

Familial hypercholesterolemia (FH) is a monogenic autosomal dominant disorder. FH is the most common hereditary cause of raised serum cholesterol levels and is associated with an increased risk of premature cardiovascular disease (CVD). This disorder is known to have a genetic cause, and effective drug therapies exist for patients with FH. Successful cascade screening, within the framework of a national screening programme, gave the Netherlands an international role as model and pioneer as far as FH detection is concerned. With the ending of this screening programme as of 1 January 2014 the care for FH patients, including screening and counselling has had to be incorporated within the basic Dutch healthcare insurance system. It is essential that detection of FH should continue in as efficient and cost-effective a manner as possible. Our proposal is that this detection should be performed and co-ordinated by those treating patients with FH so that FH screening, counselling and treatment are integrated.

The daily 10 kcal expenditure deficit: a before-and-after study on low-cost interventions in the work environment.

OBJECTIVES: To evaluate whether four types of low-cost interventions in the working environment can promote the small everyday lifestyle adaptations that can halt the epidemics of obesity and hypertension when maintained long term. DESIGN: A single-blind uninterrupted time-series intervention study consisting of four study periods: run-in (2 weeks), baseline (2 weeks), intervention (2 weeks), and after intervention 2 weeks). SETTING: University Medical Centre with over 11 000 employees, over 1000 hospital beds and over 2000 customers visiting the hospital restaurant each day. PARTICIPANTS: Hospital staff and visitors. INTERVENTIONS: (1) Point-of-decision prompts on hospital elevator doors promoting stair use. (2) Point-of-purchase prompts in the hospital restaurant promoting reduced-salt soup. (3) Point-of-purchase prompts in the hospital restaurant promoting lean croissants. (4) Reversal of the accessibility and availability of diet margarine and butter in the hospital restaurant. MAIN OUTCOME MEASURES: (1) Number of passages through 15 different parts of the hospital staircases. (2) Number and ratio of normal-salt and reduced-salt soup purchased. (3) Number and ratio of butter croissants and lean croissants purchased. (4) Number and ratio of diet margarine and butter purchased. RESULTS: Elevator signs increased the mean 24-h number of stair passages per measurement site (baseline: 992 ± 479 on week days and 208 ± 116 on weekend days) by 11.2% (95% CI 8.7% to 13.7%). This effect was maintained at least 2 weeks after the point-of-decision prompts were removed. Point-of-purchase prompts promoting low-salt soup and lean croissants did not result in altered purchase behaviour. The ratio between the purchase of margarine and butter was changed sevenfold (p<0.01) by reversing the positions of these products in the hospital restaurant. CONCLUSIONS: Healthy lifestyle adaptations in the working environment can be effectively promoted by making healthy choices easier than unhealthy ones. Educational prompts at points-of-decision moderately increase stair climbing, but do not affect healthy food choices. PROTOCOL REGISTRATION: Clinicaltrials.gov identifier number: NCT01574040.

Vascular risk management through nurse-led self-management programs.

In current clinical practice, adequate cardiovascular risk reduction is difficult to achieve. Treatment is primarily focused on clinical vascular disease and not on long-term risk reduction. Pertinent to success in vascular risk reduction are proper medication use, weight control, healthy food choices, smoking cessation, and physical exercise. Atherosclerotic vascular disease and its risk constitute a chronic condition, which poses specific requirements on affected patients and caregivers who should be aware of the chronicity. In patients with vascular disease, there is lack of awareness of their chronic condition because of the invisibility of most risk factors. In other patient groups with chronic illness, self-management programs were successful in achieving behavioral change. This strategy can also be useful for patients with vascular disease to adapt and adhere to an improved lifestyle. Self-management refers to the individual's ability to manage both physical and psychosocial consequences including lifestyle changes inherent to living with a chronic condition. Interventions that promote self-management are based on enhancing self-efficacy. In self-management, attention can be given to what is important and motivational to the individual patient. In this article the challenge of nursing care promoting self-management for patients with vascular risk and how this care can be applied will be explained. Nurses can play a central role in vascular risk management with a self-management approach for patients with chronic vascular disease. In vascular prevention clinics, nursing care can be delivered that includes medical treatment of vascular risks (hypertension, hypercholesterolemia, hyperglycemia, and hyperhomocystinemia) and counseling on promoting self-management (changes in diet, body weight, smoking habits, and level of exercise). Nursing interventions based on self-management promotion can provide a new and promising approach to actually achieve vascular risk reduction.