Cardiovascular Disease

Ramos IC, Versteegh MM, de Boer RA, Koenders JMA, Linssen GCM, Meeder JG, Rutten-van Mölken MPMH.
Value in Health. 2017;20(10):1260-1269.

OBJECTIVES
To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained.

METHODS
We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis.

RESULTS
The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647.

CONCLUSIONS
LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios.

Celano CM, Healy B, Suarez L, Levy DE, Mastromauro C, Januzzi JL, Huffman JC.
Value in Health. 2016;19(2):185-191.

OBJECTIVES
To use data from a randomized trial to determine the cost-effectiveness of a collaborative care (CC) depression and anxiety treatment program and to assess effects of the CC program on health care utilization.

METHODS
The CC intervention’s impact on health-related quality of life, depression-free days (DFDs), and anxiety-free days (AFDs) over the 24-week postdischarge period was calculated and compared with the enhanced usual care (EUC) condition using independent samples t tests and random-effects regression models. Costs for both the CC and EUC conditions were calculated on the basis of staff time, overhead expenses, and treatment materials. Using this information, incremental cost-effectiveness ratios were calculated. A cost-effectiveness acceptability plot was created using nonparametric bootstrapping with 10,000 replications, and the likelihood of the CC intervention’s cost-effectiveness was assessed using standard cutoffs. As a secondary analysis, we determined whether the CC intervention led to reductions in postdischarge health care utilization and costs.

RESULTS
The CC intervention was more costly than the EUC intervention ($209.86 vs. $34.59; z = −11.71; P P = 0.057). This translated into an incremental cost-effectiveness ratio of $3337.06 per quality-adjusted life-year saved, $13.36 per DFD, and $13.74 per AFD. Compared with the EUC intervention, the CC intervention was also associated with fewer emergency department visits but no differences in overall costs.

CONCLUSIONS
This CC intervention was associated with clinically relevant improvements, was cost-effective, and was associated with fewer emergency department visits in the 24 weeks after discharge.

Smith DH, O'Keeffe-Rosetti M, Owen-Smith AA, Rand C, Tom J, Vupputuri S, Laws R, Waterbury A, Hankerson-Dyson DD, Yonehara C, Williams A, Schneider J, Dickerson JF, Vollmer WM.
Value in Health. 2016;19(2):176-184.

OBJECTIVES
Preplanned economic analysis of a pragmatic trial using electronic-medical-record–linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular medications (i.e., statins, angiotensin-converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]).

METHODS
Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records.

RESULTS
Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls.

CONCLUSIONS
We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker’s willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline.

Einarson TR, Acs A, Ludwig C, Panton UH.
Value in Health. 2018;21(7):881-890.

BACKGROUND
Cardiovascular diseases (CVDs) constitute major comorbidities in type 2 diabetes mellitus (T2DM), contributing substantially to treatment costs for T2DM. An updated overview of the economic burden of CVD in T2DM has not been presented to date.

OBJECTIVES
To systematically review published articles describing the costs associated with treating CVD in people with T2DM.

METHODS
Two reviewers searched MEDLINE, Embase, and abstracts from scientific meetings to identify original research published between 2007 and 2017, with no restrictions on language. Studies reporting direct costs at either a macro level (e.g., burden of illness for a country) or a micro level (e.g., cost incurred by one patient) were included. Extracted costs were inflated to 2016 values using local consumer price indexes, converted into US dollars, and presented as cost per patient per year.

RESULTS
Of 81 identified articles, 24 were accepted for analysis, of which 14 were full articles and 10 abstracts. Cardiovascular comorbidities in patients with T2DM incurred a significant burden at both the population and patient levels. From a population level, CVD costs contributed between 20% and 49% of the total direct costs of treating T2DM. The median annual costs per patient for CVD, coronary artery disease, heart failure, and stroke were, respectively, 112%, 107%, 59%, and 322% higher compared with those for T2DM patients without CVD. On average, treating patients with CVD and T2DM resulted in a cost increase ranging from $3418 to $9705 compared with treating patients with T2DM alone.

CONCLUSIONS
Globally, CVD has a substantial impact on direct medical costs of T2DM at both the patient and population levels.

Guo W-Q, Li L, Su Q, Dai W-R, Ye Z-L.
Value in Health. 2017;20(10):1427-1430.

BACKGROUND
Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments.

METHODS
A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF.

RESULTS
Fifty randomized controlled trials were identified. Relative to placebo, no increased risk of HF events was seen for vildagliptin (risk ratio [RR] 0.71; 95% confidence interval [CI] 0.25–1.68), sitagliptin (RR 0.86; CI 0.43–1.57), or saxagliptin (RR 0.84; 95% CI 0.33–1.61), but alogliptin was associated with a higher risk of HF (RR 2.13; 95% CI 1.06–6.26). Vildagliptin and sitagliptin were associated with a significantly decreased risk of HF compared with alogliptin. Vildagliptin had the highest probability to be the safest option with regard to the risk of HF (49.18%), followed by saxagliptin (26.56%), sitagliptin (20.76%), linagliptin (0.25%), and alogliptin (0.12%). A statistically significant inconsistency was noted in some comparisons.

CONCLUSIONS
The risk of HF needs to be taken into account when prescribing DPP-4 inhibitors. Evidence suggests that vildagliptin may be the least harmful agent with regard to the risk of HF. However, a statistically significant inconsistency was identified in the Bayesian network meta-analysis. Therefore, further studies are warranted to evaluate the cardiovascular safety of DPP-4 inhibitors.

Augustovski F, Chaparro M, Palacios A, Shi L, Beratarrechea A, Irazola V, Rubinstein A, Mills K, He J, Riviere AP.
Value in Health. 2018;21(12):1357-1364.

BACKGROUND
A recent cluster randomized trial evaluating a multicomponent intervention showed significant reductions in blood pressure in low-income hypertensive subjects in Argentina.

OBJECTIVE
To assess the cost-effectiveness of this intervention.

METHODS
A total of 1432 hypertensive participants were recruited from 18 primary health care centers. The intervention included home visits led by community health workers, physician education, and text messaging. Resource use and quality of life data using the three-level EuroQol five-dimensional questionnaire were prospectively collected. The study perspective was that of the public health care system, and the time horizon was 18 months. Intention-to-treat analysis was used to analyze cost and health outcomes (systolic blood pressure [SBP] change and quality-adjusted life-years [QALYs]). A 1 time gross domestic product per capita per QALY was used as the cost-effectiveness threshold (US $14,062).

RESULTS
Baseline characteristics were similar in the two arms. QALYs significantly increased by 0.06 (95% confidence interval [CI] 0.04–0.09) in the intervention group, and SBP net difference favored the intervention group: 5.3 mm Hg (95% CI 0.27–10.34). Mean total costs per participant were higher in the intervention arm: US $304 in the intervention group and US $154 in the control group (adjusted difference of US $140.18; 95% CI US $75.41–US $204.94). The incremental cost-effectiveness ratio was $3299 per QALY (95% credible interval 1635–6099) and US $26 per mm Hg of SBP (95% credible interval 13–46). Subgroup analysis showed that the intervention was cost-effective in all prespecified subgroups (age, sex, cardiovascular risk, and body mass index).

CONCLUSIONS
The multicomponent intervention was cost-effective for blood pressure control among low-income hypertensive patients.

Peñaloza-Ramos MC, Jowett S, Sutton AJ, McManus RJ, Barton P.
Value in Health. 2018;21(3):351-363.

BACKGROUND
Management of hypertension can lead to significant reductions in blood pressure, thereby reducing the risk of cardiovascular disease. Modeling the course of cardiovascular disease is not without complications, and uncertainty surrounding the structure of a model will almost always arise once a choice of a model structure is defined.

OBJECTIVE
To provide a practical illustration of the impact on the results of cost-effectiveness of changing or adapting model structures in a previously published cost-utility analysis of a primary care intervention for the management of hypertension Targets and Self-Management for the Control of Blood Pressure in Stroke and at Risk Groups (TASMIN-SR).

METHODS
The case study assessed the structural uncertainty arising from model structure and from the exclusion of secondary events. Four alternative model structures were implemented. Long-term cost-effectiveness was estimated and the results compared with those from the TASMIN-SR model.

RESULTS
The main cost-effectiveness results obtained in the TASMIN-SR study did not change with the implementation of alternative model structures. Choice of model type was limited to a cohort Markov model, and because of the lack of epidemiological data, only model 4 captured structural uncertainty arising from the exclusion of secondary events in the case study model.

CONCLUSIONS
The results of this study indicate that the main conclusions drawn from the TASMIN-SR model of cost-effectiveness were robust to changes in model structure and the inclusion of secondary events. Even though one of the models produced results that were different to those of TASMIN-SR, the fact that the main conclusions were identical suggests that a more parsimonious model may have sufficed.