Ranolazine in patients with type 2 diabetes and chronic angina: A cost-effectiveness analysis and assessment of health-related quality-of-life.

BACKGROUND: Type 2 diabetes (T2D) is associated with a high burden of angina. Ranolazine has been shown to reduce angina frequency versus placebo in patients with T2D and stable angina. We sought to estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) versus SoC alone in patients with T2D and stable, but symptomatic coronary disease despite treatment with 1-2 antianginals. METHODS: A Markov model was developed and evaluated using cohort simulation. The model utilized a US societal perspective, 1-month cycle length and 1-year time horizon and was developed to estimate the cost-effectiveness of ranolazine versus SoC. Patients entered the model in 1 of 4 angina frequency health states based on baseline Seattle Angina Questionnaire Angina Frequency scores (100 = no; 61-99 = monthly; 31-60 = weekly; 0-30 = daily) and could transition between health states (first cycle only) or to death (any cycle) based on probabilities derived from the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina trial. RESULTS: Our model estimated patients treated with ranolazine lived a mean of 0.728 quality adjusted life years (QALYs) at a cost of $16,654. Those not receiving ranolazine lived a mean of 0.702 QALYs and incurred costs of $15,476. The incremental cost-effectiveness ratio for the addition of ranolazine to SoC was $45,308/QALY. Short Form-36 data suggest improvements in patients' bodily pain drove the gain in QALYs associated with ranolazine (2.73 versus 3.96, p = 0.01). CONCLUSION: Our model suggests the addition of ranolazine to SoC is likely cost-effective from a US societal perspective for the treatment of patients with T2D and stable, symptomatic coronary disease despite treatment with 1-2 antianginals.

Socioeconomic inequality in medication persistence in primary and secondary prevention of coronary heart disease - A population-wide electronic cohort study.

BACKGROUND: Coronary heart disease (CHD) mortality in England fell by 36% between 2000 and 2007 and it is estimated that approximately 50% of the fall was due to improved treatment uptake. Marked socio-economic inequalities in CHD mortality in the United Kingdom (UK) remain, with higher age-adjusted rates in more deprived groups. Inequalities in the persistence of medication for primary and secondary prevention of CHD may contribute to the observed social gradient and we investigated this possibility in the population of Wales (UK). METHODS AND FINDINGS: An electronic cohort of individuals aged over 20 (n = 1,199,342) in Wales (UK) was formed using linked data from primary and secondary care and followed for six years (2004-2010). We identified indications for medication (statins, aspirin, ACE inhibitors, clopidogrel) recommended in UK National Institute for Clinical Excellence (NICE) guidance for CHD (high risk, stable angina, stable angina plus diabetes, unstable angina, and myocardial infarction) and measured the persistence of indicated medication (time from initiation to discontinuation) across quintiles of the Welsh Index of Multiple Deprivation, an area-based measure of socio-economic inequality, using Cox regression frailty models. In models adjusted for demographic factors, CHD risk and comorbidities across 15 comparisons for persistence of the medications, none favoured the least deprived quintile, two favoured the most deprived quintile and 13 showed no significant differences. CONCLUSIONS: During our study period (2004-2010) we found no significant evidence of socio-economic inequality in the persistence of recommended medication for primary and secondary prevention of CHD.

Economic Impact of Subsequent Depression in Patients With a New Diagnosis of Stable Angina: A Population-Based Study.

BACKGROUND: Depression is strongly linked to increased morbidity and mortality in patients with chronic stable angina; however, its associated healthcare costs have been less well studied. Our objective was to identify the characteristics of chronic stable patients found to have depression and to determine the impact of an occurrence of depression on healthcare costs within 1 year of a diagnosis of stable angina. METHODS AND RESULTS: In this population-based study conducted in Ontario, Canada, we identified patients diagnosed with stable angina based on angiogram between October 1, 2008, and September 30, 2013. Depression was ascertained by physician billing codes and hospital admission diagnostic codes contained within administrative databases. The primary outcome was cumulative mean 1-year healthcare costs following index angiogram. Generalized linear models were developed with a logarithmic link and γ distribution to determine predictors of cost. Our cohort included 22 917 patients with chronic stable angina. Patients with depression had significantly higher mean 1-year healthcare costs ($32 072±$41 963) than patients without depression ($23 021±$25 741). After adjustment for baseline comorbidities, depression was found to be a significant independent predictor of cost, with a cost ratio of 1.33 (95% confidence interval, 1.29-1.37). Higher costs in depressed patients were seen in all healthcare sectors, including acute and ambulatory care. CONCLUSIONS: Depression is an important driver of healthcare costs in patients following a diagnosis of chronic stable angina. Further research is needed to understand whether improvements in the approach to diagnosis and treatment of depression will translate to reduced expenditures in this population.

Non-Communicable Disease Clinical Practice Guidelines in Brazil: A Systematic Assessment of Methodological Quality and Transparency.

BACKGROUND: Annually, non-communicable diseases (NCDs) kill 38 million people worldwide, with low and middle-income countries accounting for three-quarters of these deaths. High-quality clinical practice guidelines (CPGs) are fundamental to improving NCD management. The present study evaluated the methodological rigor and transparency of Brazilian CPGs that recommend pharmacological treatment for the most prevalent NCDs. METHODS: We conducted a systematic search for CPGs of the following NCDs: asthma, atrial fibrillation, benign prostatic hyperplasia, chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease and/or stable angina, dementia, depression, diabetes, gastroesophageal reflux disease, hypercholesterolemia, hypertension, osteoarthritis, and osteoporosis. CPGs comprising pharmacological treatment recommendations were included. No language or year restrictions were applied. CPGs were excluded if they were merely for local use and referred to NCDs not listed above. CPG quality was independently assessed by two reviewers using the Appraisal of Guidelines Research and Evaluation instrument, version II (AGREE II). MAIN FINDINGS: "Scope and purpose" and "clarity and presentation" domains received the highest scores. Sixteen of 26 CPGs were classified as low quality, and none were classified as high overall quality. No CPG was recommended without modification (77% were not recommended at all). After 2009, 2 domain scores ("rigor of development" and "clarity and presentation") increased (61% and 73%, respectively). However, "rigor of development" was still rated < 30%. CONCLUSION: Brazilian healthcare professionals should be concerned with CPG quality for the treatment of selected NCDs. Features that undermined AGREE II scores included the lack of a multidisciplinary team for the development group, no consideration of patients' preferences, insufficient information regarding literature searches, lack of selection criteria, formulating recommendations, authors' conflict of interest disclosures, and funding body influence.

The impact of socio-economic status on all-cause mortality after percutaneous coronary intervention: an observational cohort study of 13,770 patients.

AIMS: The relation between socio-economic status (SES) and outcomes after percutaneous coronary intervention (PCI) has not been established. We sought to determine whether or not socio-economic status impacts on prognosis after PCI. METHODS AND RESULTS: This was an observational cohort study of 13,770 consecutive patients who underwent PCI at a single centre between 2005 and 2011. Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0-5.1) years and the primary outcome was all-cause mortality. Patients in Q5 (most deprived) were younger, more commonly South Asian, and had higher rates of smoking, diabetes mellitus, renal impairment, previous MI, and previous PCI than patients in Q1. Rates of long-term mortality increased progressively across the five quintiles of IMD score in a linear fashion (p=0.0004), as did rates of recurrent MI, target vessel revascularisation, and CABG. The difference in mortality rates persisted after adjustment for other potential confounding factors after multivariate analysis (Q5 vs. Q1: HR 1.93, 95% CI: 1.38-2.69). CONCLUSIONS: In this large contemporary cohort of patients receiving PCI, socio-economic status was associated with prognosis in a linear fashion.

Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial.

BACKGROUND: Ranolazine has been previously shown to improve exercise capacity and symptoms in patients with severe chronic angina treated with standard doses of beta-blockers and calcium-channel blockers, without a significant effect on heart rate or blood pressure. OBJECTIVE: The purpose of this study was to assess whether the benefit of ranolazine extends to the subgroup of angina patients treated with maximally-tolerated doses of beta-blockers or calcium blockers. METHODS AND RESULTS: In this post-hoc analysis, 258 patients from the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial were considered as treated with maximally-tolerated doses of beta-blockers or calcium-channel blockers (systolic blood pressure (SBP) ≤ 100 mm Hg, and/or a resting heart rate ≤ 60 beats per minute, and/or an ECG PR interval ≥ 200 msec). Change from baseline in total exercise duration after 12 weeks compared to placebo were 34.5 (95% CI 0.8; 68.1) sec (p = 0.045) with ranolazine (750/1000 mg bid) at trough drug levels and 46.3 (13.5; 79.1) (p = 0.006) at peak drug levels. The number of angina attacks per week compared to baseline were reduced compared to placebo (-2.3 ± 0.3 vs -0.9 ± 0.6 (p < 0.001)). The effects of ranolazine 750 mg bid and 1000 mg bid were similar and the beneficial effects of ranolazine in this subgroup of maximally-treated patients were consistent with those not on maximally-tolerated doses of the background therapy. CONCLUSION: Ranolazine is effective for the symptomatic treatment of patients with stable angina on background therapy with maximally-tolerated doses of first line anti-anginal therapies.