Long-Term (3 Years) Outcomes of Ranolazine Therapy for Refractory Angina Pectoris (from the Ranolazine Refractory Registry).

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, ß blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to 1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were less common with ranolazine users compared with conventional users (all-cause: HR 0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001), and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In conclusion, ranolazine users had lower rates of coronary artery bypass grafting and all-cause and AF hospitalizations, but higher rates of percutaneous coronary intervention and hospitalizations due to acute coronary syndrome compared with conventional antianginal users. Healthcare costs were similar between ranolazine and conventional antianginal users.

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.

A literature review to evaluate the economic value of ranolazine for the symptomatic treatment of chronic angina pectoris.

To conduct a systematic review of the evidence regarding the economic value of ranolazine relative to standard-of-care (SOC) for the treatment of symptomatic chronic stable angina (CSA). Electronic databases were searched using relevant keywords. The identified studies were independently reviewed by two investigators against pre-determined inclusion and exclusion criteria. Their data were extracted using a relevant form and consequently were synthesized. Studies were also evaluated using the Quality of Health Economic Studies scale. The main outcomes considered were the cost and effectiveness for each comparator and the incremental cost per quality-adjusted-life year (QALY) gained. Six studies were included in the review. Five of these assessed the cost-utility of ranolazine added to SOC, compared to SOC alone, using decision trees or Markov models whereas one was a retrospective cost evaluation study. The analysis was conducted from a payer perspective in five studies and from a societal perspective in one study with the time horizon varying between six months and a year. The incremental cost-effectiveness ratio (ICER), ranged from €4000 to €15,000 per QALY gained. Ranolazine appears to be dominant or cost-effective, mainly due to its ability to decrease angina-related hospitalizations and also due to a marginal improvement in quality of life. The acquisition cost of ranolazine was the variable with the greatest impact upon the ICER. The existing evidence, although limited, indicates that ranolazine may be a dominant or cost-effective therapy option, for the treatment of patients with symptomatic CSA. Further research is required to evaluate the cost-effectiveness of ranolazine.

Ranolazine for the symptomatic treatment of patients with chronic angina pectoris in Greece: a cost-utility study.

BACKGROUND: To conduct an economic evaluation comparing ranolazine as add-on therapy to standard-of-care (SoC) with SoC alone in patients with stable angina who did not respond adequately to first line therapy, in Greece. METHODS: A decision tree model was locally adapted in the Greek setting to evaluate the cost-utility of ranolazine during a 6-month period. The analysis was conducted from a third-party payer perspective. The clinical inputs were extracted from the published literature. The cost inputs considered in the model reflect drug acquisition, hospitalizations, vascular interventions and monitoring of patients. The resource utilization data were obtained from 3 local experts. All costs refer to the year 2014. Cost-effectiveness was assessed by means of the incremental cost per quality adjusted life year (QALY) gained with the ranolazine as add-on therapy relative to SoC alone (ICER). Probabilistic sensitivity analysis (PSA) was performed. RESULTS: Ranolazine as add-on therapy was more costly compared to SoC alone, as the 6-month total cost per patient was €1170 and € 984, respectively. Patients received ranolazine plus SoC and SoC alone gained 0.3155 QALYs and 0.2752 QALYs, respectively. Ranolazine plus SoC resulted in an ICER equal to €4620 per QALY gained, well below the threshold of €34,000 per QALY gained. The PSA showed that the likelihood of ranolazine plus SoC being cost-effective at the threshold of €34,000 per QALY gained was 100 %. CONCLUSIONS: Τhe results suggest that ranolazine as add-on treatment may be a cost-effective alternative for the symptomatic treatment of patients with chronic stable angina in Greece.

Ranolazine for the treatment of chronic stable angina: a cost-effectiveness analysis from the UK perspective.

OBJECTIVES: To estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week. SETTING: An economic model utilising a UK health system perspective, a 1-month cycle-length and a 1-year time horizon. PARTICIPANTS: Patients with stable coronary disease experiencing ≥3 attacks/week starting in 1 of 4 angina frequency health states based on Seattle Angina Questionnaire Angina Frequency (SAQAF) scores (100=no; 61-99=monthly; 31-60=weekly; 0-30=daily angina). INTERVENTION: Ranolazine added to SoC or SoC alone. Patients were allowed to transition between SAQAF states (first cycle only) or death (any cycle) based on probabilities derived from the randomised, controlled Efficacy of Ranolazine in Chronic Angina trial and other studies. Patients not responding to ranolazine in month 1 (not improving ≥1 SAQAF health state) discontinued ranolazine and were assumed to behave like SoC patients. PRIMARY AND SECONDARY OUTCOMES MEASURES: Costs (£2014) and quality-adjusted life-years (QALYs) for patients receiving and not receiving ranolazine. RESULTS: Ranolazine patients lived a mean of 0.701 QALYs at a cost of £5208. Those not receiving ranolazine lived 0.662 QALYs at a cost of £5318. The addition of ranolazine to SoC was therefore a dominant economic strategy. The incremental cost-effectiveness ratio was sensitive to ranolazine cost; exceeding £20,000/QALY when ranolazine's cost was >£203/month. Ranolazine remained a dominant strategy when indirect costs were included and mortality rates were assumed to increase with worsening severity of SAQAF health states. Monte Carlo simulation found ranolazine to be a dominant strategy in ∼71% of 10,000 iterations. CONCLUSIONS: Although UK-specific data on ranolazine's efficacy and safety are lacking, our analysis suggest ranolazine added to SoC in patients with weekly or daily angina is likely cost-effective from a UK health system perspective.

Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions.

Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a ß blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.