Lipoprotein(a) and cardiovascular disease: sifting the evidence to guide future research.

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease including coronary heart disease, peripheral arterial disease, ischaemic stroke, and calcific aortic valve stenosis. Clinical trials of specific and potent Lp(a)-lowering drugs are currently underway. However, in clinical practice, widespread assessment of Lp(a) is still lacking despite several guideline recommendations to measure Lp(a) at least once in a lifetime in all adults to identify those at high or very high risk due to elevated levels. The present review provides an overview of key findings from observational and genetic Lp(a) studies, highlights the main challenges in observational Lp(a) studies, and proposes a minimum set of requirements to enhance the quality and harmonize the collection of Lp(a)-related data. Adherence to the recommendations set forth in the present manuscript is intended to enhance the quality of future observational Lp(a) studies, to better define thresholds for increased risk, and to better inform clinical trial design. The recommendations can also potentially assist in the interpretation and generalization of clinical trial findings, to improve care of patients with elevated Lp(a) and optimize treatment and prevention of cardiovascular disease.

Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank.

BACKGROUND AND AIMS: Elevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights into the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort. METHODS: This was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a). RESULTS: The study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period. CONCLUSIONS: The association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.

Burden of lipoprotein(a) for patients with atherosclerotic cardiovascular disease: A retrospective analysis from the United States.

BACKGROUND: Lipoprotein(a) (Lp(a)) is an inherited, independent, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To assess the burden of elevated Lp(a) for patients with ASCVD in a real-world setting in the United States. METHODS: This retrospective cohort study assessed US patients with available Lp(a) measurement and established ASCVD using Optum's Clinformatics Data Mart database (2007-2020). Index date was defined as the first diagnosis of an ASCVD event. Patient demographics, medications, health care resource utilization (HCRU), and occurrence of cardiovascular events were assessed for patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels, within the first year of index date. HCRU was characterized by inpatient hospitalization, inpatient length of stay (LOS), outpatient visits, and emergency department (ED) visits. All comparative analyses of patients with elevated (≥150 nmol/L) vs normal (≥65 nmol/L) Lp(a) levels within the first year of index date were adjusted for age, sex, baseline statin use, and diabetes. RESULTS: 8,372 patients with ASCVD and Lp(a) measurement in nmol/L were included in this study. Patient demographics and baseline clinical characteristics were similar among those with normal and elevated Lp(a). However, the proportion of patients receiving statins and ß-blockers at baseline were significantly higher in the elevated vs normal Lp(a) group (54.76% vs 42.91%, P < 0.0001, and 30.92% vs 27.32%, P = 0.0183, respectively). At 1 year of follow-up, the rates per 100 person-years for ASCVD-related inpatient hospitalizations, outpatient hospitalizations, and ED visits were higher among patients with elevated Lp(a) compared with normal Lp(a) (13.33 vs 9.46, 89.08 vs 85.10, and 2.89 vs 2.29, respectively). The mean LOS per ASCVD-related hospitalization was 7.21 days in the elevated and 6.26 days in the normal Lp(a) group (P = 0.3462). During the 1-year post-index follow-up period, 15% of patients in the elevated Lp(a) group required revascularization compared with 10% of patients in the normal Lp(a) group (P = 0.0002). The odds of composite myocardial infarction, ischemic stroke, and revascularization occurrence of events within the first year of index was significantly higher in the elevated Lp(a) group compared with the normal Lp(a) group (1.46; 95% CI = 1.20-1.77; P < 0.05). CONCLUSIONS: HCRU within the first year of ASCVD diagnosis is substantial among patients with ASCVD and elevated Lp(a). Relatively higher rates of inpatient hospitalizations, increased LOS per hospitalization, and requirement of revascularization procedures within the first year of ASCVD index diagnosis were observed in patients with elevated Lp(a) compared with normal Lp(a) levels. Lp(a) testing in routine clinical practice could help in identification of high-risk patients with ASCVD and play an important role in the overall cardiovascular risk management, aiming to reduce the HCRU associated with ASCVD. DISCLOSURES: Ms Fonseca, Dr Laguna, Dr Itani, Dr Rachel Studer, and Dr Ferber are employees of Novartis Pharma AG, Basel, Switzerland. Ms Byrne is an employee of Novartis AG, Dublin, Ireland. Dr Costa-Scharplatz is an employee of Novartis Sweden AB, Stockholm, Sweden. Dr Heo and Ms Dillon are employees of Genesis Research. Genesis Research was commissioned to conduct the study (data extraction and analysis) on behalf of Novartis Pharma AG.

Real-world comparative effectiveness of ARNI versus ACEi/ARB in HF with reduced or mildly reduced ejection fraction.

AIMS: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF). METHODS: Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016-31 December 2020). Eligible ARNI:ACEi/ARB patients (n = 7275:24,604) had a left ventricular EF < 50%. Mortality and hospitalizations with ARNI (≤ 3 months pre-/post-1 April 2016 index [SwedeHF]; n = 1506) versus ACEi/ARB (≤ 3 months post-index; n = 17,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2/1:3 with, and 1:2 without clinical variables). RESULTS: ARNI induced a 23% reduction in all-cause mortality versus ACEi/ARB (1:1 hazard ratio [HR; 95% confidence interval (CI)]: 0.77 [0.63-0.95], p = 0.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54-1.09], p = 0.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91-1.13]; p = 0.76; 1.01 [0.91-1.15]; p = 0.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi/ARB (HR 0.90 [95% CI 0.82-0.99], p = 0.026), but not CV-related mortality (HR 1.04 [95% CI 0.89-1.22], p = 0.63). CONCLUSIONS: In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi/ARB.

Clinical characteristics and mortality of patients with heart failure in Southern Sweden from 2013 to 2019: a population-based cohort study.

OBJECTIVES: To describe clinical characteristics and prognosis related to heart failure (HF) phenotypes in a community-based population by applying a novel algorithm to obtain ejection fractions (EF) from electronic medical records. DESIGN: Retrospective population-based cohort study. SETTING: Data were collected for all patients with HF in Southwest Sweden. The region consists of three acute care hospitals, 40 inpatient wards, 2 emergency departments, 30 outpatient specialty clinics and 48 primary healthcare. PARTICIPANTS: 8902 patients had an HF diagnosis based on the International Classification of Diseases, Tenth Revision during the study period. Patients <18 years as well as patients declining to participate were excluded resulting in a study population of 8775 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was distribution of HF phenotypes by echocardiography. The secondary outcome measures were 1 year all-cause mortality and HR for all-cause mortality using Cox regression models. RESULTS: Out of 8775 patients with HF, 5023 (57%) had a conclusive echocardiography distributed into HF with reduced EF (35%), HF with mildly reduced EF (27%) and HF with preserved EF (38%). A total of 43% of the cohort did not have a conclusive echocardiography, and therefore no defined phenotype (HF-NDP). One-year all-cause mortality was 42% within the HF-NDP group and 30% among those with a conclusive EF. The HR of all-cause mortality in the HF-NDP group was 1.27 (95% CI 1.17 to 1.37) when compared with the confirmed EF group. There was no significant difference in survival within the HF phenotypes. CONCLUSIONS: This population-based study showed a distribution of HF phenotypes that varies from those in selected HF registries, with fewer patients with HF with reduced EF and more patients with HF with preserved EF. Furthermore, 1-year all-cause mortality was significantly higher among patients with HF who had not undergone a conclusive echocardiography at diagnosis, highlighting the importance of correct diagnostic procedure to improve treatment strategies and outcomes.

Healthcare resource utilisation and costs associated with a heart failure diagnosis: a retrospective, population-based cohort study in Sweden.

OBJECTIVES: To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. DESIGN: Retrospective, non-interventional cohort study. SETTING: Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Västerbotten). PARTICIPANTS: Patients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. OUTCOME MEASURES: HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. RESULTS: Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs. CONCLUSIONS: HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.

Recurrent heart failure hospitalizations increase the risk of cardiovascular and all-cause mortality in patients with heart failure in Sweden: a real-world study.

AIMS: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. METHODS AND RESULTS: Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all-cause mortality were evaluated. A time-dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction-based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all-cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all-cause mortality increased approximately six-fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24-7.48] and 5.59 [4.70-6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. CONCLUSIONS: There is a strong association between recurrent HFHs and CV and all-cause mortality, with the risk increasing progressively with each recurrent HFH.

Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants.

AIMS: The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. METHODS AND RESULTS: A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with ≥1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. CONCLUSIONS: Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.

Burden of migraine in Finland: health care resource use, sick-leaves and comorbidities in occupational health care.

BACKGROUND: The highest prevalence of migraine is detected among people who are of working age. The aim of this study was to assess the burden of migraine in an occupational health care setting using real world data collected as a part of routine clinical practice. METHODS: This retrospective register study included migraineurs using occupational health care at the private health care provider Terveystalo. An age and gender matched control population was established for comparison. Electronic medical records were assessed for overall and migraine related health care visits, sick-leaves and comorbidities. Stratification to acute and prophylactic treatment groups along with prophylactic treatment lines was based on prescriptions. RESULTS: Among the 369,383 individuals in the study cohort, 7.4% women and 2.1% men were identified having a diagnosis of migraine. Prophylactic medication was prescribed to 13% of migraine patients and exclusively acute medication to 37%. Although migraine related visits and sick-leave days were significantly lower than overall visits or sick-leave days, both increased by prophylactic treatment line. The number of visits rose from 13.8 to 26.2 and sick-leave days from 16.8 to 30.4 per patient-year, in those without prophylaxis vs. ≥3 prophylactic treatments. Moreover, migraine patients had 1.7-fold increase in visits and 1.8-fold increase in sick leave days on average per patient-year, when compared to the control population. Depression and anxiety were 1.8-fold more common among patients with migraine, and the frequency also increase by treatment line. CONCLUSIONS: Migraine burden increased by each failed treatment line and was associated with increased comorbidity. In addition, migraine patients had significantly higher extent of visits and sick-leave days as well as extent of comorbidities when compared to their age- and gender-matched counterparts.

Economic burden of COPD in a Swedish cohort: the ARCTIC study.

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting. Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed. Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013. Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.

Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD: FLAME-based modelling in a Swedish population.

BACKGROUND: This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. METHODS: A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed. RESULTS: IND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers. CONCLUSION: IND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year.

Cost-Effectiveness of Glycopyrronium Bromide Compared with Tiotropium in Patients with Chronic Obstructive Pulmonary Disease in Sweden.

OBJECTIVES: The objective of this study was to compare the cost effectiveness of once-daily Seebri Breezhaler(®) (glycopyrronium bromide) 50 µg with Spiriva(®) (tiotropium bromide) 18 µg in the maintenance treatment of chronic obstructive pulmonary disease (COPD) in the Swedish setting. METHODS: A previously published COPD Markov model accounting for disease progression and treatment discontinuation was used. Disease progression included the annual decline in forced expiratory volume in the first second (FEV1) and occurrence of any exacerbations. Efficacy in the model consisted of FEV1 improvement between baseline and 12 weeks and the annual risk ratio of having an exacerbation compared to placebo. These clinical efficacy inputs were derived from a 1-year head-to-head trial comparing glycopyrronium 50 µg to tiotropium 18 µg. Utility values and cost estimates were obtained from the literature. The base-case analysis was performed for a 3-year time horizon. Cost and effects were discounted with 3% in accordance to Swedish guidelines. Uncertainty was assessed by one-way and probabilistic sensitivity analyses. RESULTS: Glycopyrronium was found to be less costly and more effective than tiotropium in moderate to severe COPD patients with cost savings of 5197 Swedish kronor (€570, US$725) per patient over a 3-year time horizon. The probabilistic sensitivity analysis indicated that over 99% of the iterations produced dominant results for glycopyrronium. CONCLUSION: Glycopyrronium bromide 50 µg once daily can be considered a cost effective alternative to tiotropium bromide 18 µg once daily in the maintenance treatment of COPD patients in Sweden.

Cost-effectiveness of the LABA/LAMA dual bronchodilator indacaterol/glycopyrronium in a Swedish healthcare setting.

BACKGROUND: Indacaterol/glycopyrronium (IND/GLY) is a once-daily inhaled fixed-dose combination of indacaterol (IND), a long-acting ß2-adrenergic agonist (LABA), and glycopyrronium (GLY), a long-acting muscarinic antagonist (LAMA) for use as maintenance treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults. OBJECTIVE: To determine the economic benefits of IND/GLY compared with the free combination of indacaterol and glycopyrronium (IND + GLY), and with the fixed-dose combination of salmeterol/fluticasone (SFC), in a moderate-to-severe COPD population with low-exacerbation risk. The model-based analysis extrapolated results up to lifetime time horizon and calculated costs per quality-adjusted life year. METHODS: Assuming equal efficacy, a cost-minimisation analysis compared IND/GLY vs IND + GLY using model inputs from the double-blind, randomised SHINE trial. The double-blind, randomised ILLUMINATE and TORCH trials were used to analyse cost-effectiveness versus SFC. To consider ICS-related pneumonia events, published odds ratio comparing an ICS-exposed group to a control group of COPD patients was used. Direct and indirect drug costs as well as drug acquisition costs (in Swedish Krona [SEK]) were derived from published Swedish sources. Cost and effects were discounted with 3%. Uncertainty was assessed by one-way and probabilistic sensitivity analyses (PSA). RESULTS: IND/GLY was cost-saving vs IND + GLY with incremental savings of SEK (EUR) 768 (85), and 3309 (368) per patient over one and five years. IND/GLY was found to be less costly and more effective compared to SFC with cost savings of SEK (EUR) 2744 (303), 8854 (976), 13,938 (1536), 27,495 (3031) and 43,033 (4744) over one, three, five, ten years and lifetime. The PSA indicated that all iterations produced dominant results for IND/GLY. CONCLUSION: IND/GLY is cost-minimising vs IND + GLY and dominates SFC in the maintenance treatment of COPD patients in Sweden. Encouraging dual bronchodilator therapy over an ICS-containing combination results in lower total costs and better outcomes compared to combination therapy including fluticasone in moderate-to-severe COPD patients with low exacerbation risk.

Cost-effectiveness analysis of rosuvastatin versus atorvastatin, simvastatin, and pravastatin from a Canadian health system perspective.

OBJECTIVE: The primary objective of this study was to assess the cost-effectiveness of the most commonly prescribed doses of rosuvastatin, atorvastatin, simvastatin, and pravastatin for managing various lipid parameters in patients with hypercholesterolemia over a 1-year time horizon from a Canadian health care perspective. METHODS: Incremental cost-effectiveness ratios (ICERs) were estimated for branded rosuvastatin compared with branded atorvastatin, generic simvastatin, and generic pravastatin in patients with hypercholesterolemia in terms of percent reduction in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, as well as in TC, HDL-C, triglycerides (TG), apolipoprotein (Apo) B, the ApoB/ApoA-I ratio, and attainment of the Canadian LDL-C goal. The pharmacoeconomic model was constructed for a 1-year time horizon using efficacy data from a randomized, open-label trial including 2268 adults and the wholesale acquisition costs of branded rosuvastatin and atorvastatin and generic simvastatin and pravastatin in British Columbia. RESULTS: The most commonly prescribed doses of each of the 4 statins in British Columbia were as follows: rosuvastatin 10 mg (75.8% of all rosuvastatin doses); atorvastatin 10 and 20 mg (46.4% and 35.3%, respectively, of all atorvastatin doses); simvastatin 20 and 40 mg (42.5% and 31.8%, respectively, of all simvastatin doses); and pravastatin 20 and 40 mg (55.0% and 34.1%, respectively, of all pravastatin doses). Rosuvastatin 10 mg was dominant (ie, was more effective at a lower cost) relative to atorvastatin 10 and 20 mg, simvastatin 20 and 40 mg, and pravastatin 40 mg in terms of reductions in LDL-C, TC/ HDL-C ratio, TC, ApoB, and ApoB/ApoA-I ratio, increases in HDL-C, and attainment of the LDL-C goal. Compared with pravastatin 20 mg, the ICER per percent reduction in LDL-C, TC/HDL-C ratio, TC, TG, ApoB, or ApoB/ApoA-I or increase in HDL-C ranged from $3.89 to $26.07; the value for 1 additional patient achieving the LDL-C goal was $419.75. When the statin doses were aggregated based on the Canadian statin-utilization pattern, rosuvastatin was dominant relative to atorvastatin on all effectiveness measures evaluated. When rosuvastatin was compared with generic simvastatin and pravastatin, the annual costs for 1 additional patient achieving the LDL-C goal were $144.51 and $373.91, respectively. Based on the sensitivity analysis, rosuvastatin was associated with the highest probability of cost-effectiveness compared with the other statins over a broad range of monetary values per unit of clinical effect. CONCLUSION: When percent changes in lipid parameters and rates of LDL-C goal attainment were considered in patients with hypercholesterolemia in British Columbia, rosuvastatin 10 mg was more cost-effective than the most frequently used doses of atorvastatin (10 and 20 mg), generic simvastatin (20 and 40 mg), and generic pravastatin (20 and 40 mg).

Cost-effectiveness of pharmacogenetic testing to predict treatment response to angiotensin-converting enzyme inhibitor.

OBJECTIVE: This study aimed to assess the potential cost-effectiveness of testing patients with nephropathies for the I/D polymorphism before starting angiotensin-converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a healthcare perspective. METHODS: We used a combination of a decision analysis and Markov modeling technique to evaluate the potential economic value of this pharmacogenetic test by preventing unfavorable treatment in patients with nephropathies. The estimation of the predictive value of the I/D polymorphism is based on a systematic review showing that DD carriers tend to respond well to ACE inhibitors, while II carriers seem not to benefit adequately from this treatment. Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients with end-stage renal disease (ESRD) prevented and the differences in the incremental costs and incremental effect expressed as life-years free of ESRD. A probabilistic sensitivity analysis was conducted to determine the robustness of the results. RESULTS: Compared with unselective treatment, testing patients for their ACE genotype could save 12 patients per 1000 from developing ESRD during the 3 years covered by the model. As the mean net cost savings was euro 356,000 per 1000 patient-years, and 9 life-years free of ESRD were gained, selective treatment seems to be dominant. CONCLUSION: The study suggests that genetic testing of the I/D polymorphism in patients with nephropathy before initiating ACE therapy will most likely be cost-effective, even if the risk for II carriers to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD carriers. Further studies, however, are required to corroborate the difference in treatment response between ACE genotypes, before genetic testing can be justified in clinical practice.