Coronary Artery Disease
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

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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 β 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.

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Methods

To compare differences between ranolazine and traditional AA therapies, we conducted a retrospective, quasi-experimental between-group analysis using propensity matching. The data source was the Clinformatics Data Mart representing a commercially available data source for research purposes from United Healthcare's nationwide patient population. The patient population included United Healthcare's fully insured, Medicaid, and Medicare Advantage population representing 49 million unique subjects.

Results

From January 1, 2008, through December 31, 2012, of those meeting the inclusion criteria, 8,008 were identified with CSA receiving either a BB (n = 2,002), CCB (n = 2,002), LAN (n = 2,002), or ranolazine (n = 2,002; Figure 2). As seen in Table 1, baseline characteristics were well matched between groups. Most patients were men, had a mean age of 66 years, and resided within the Southern United States. The type of medical coverage varied between therapeutic treatment groups. For private and

Discussion

As CSA is closely tied to coronary artery disease (CAD) and its complications, this particular CV condition has been associated with a large increase in health care resource utilization. In a post hoc analysis of the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation ACS–Thrombolysis in Myocardial Infarction 36 trial, Arnold et al7 found that compared to those without angina, patients with daily angina after an ACS event had a 2-fold increase in health care resource

Disclosures

Drs. Hartsfield and Koch are employed by Gilead Sciences. None of the other authors have conflicts of interest to disclose.

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    A retrospective analysis of 4,545 unmatched patients with chronic stable angina found that patients with add-on ranolazine were less likely to have a revascularization procedure in the 6 months following index prescription than those with add-on LANs (p <0.001) or those on a BB/CCB combination (p <0.001).11 Similarly, a propensity-matched study of 8,008 patients found that patients on second line BBs or LANs had higher odds (odds ratio, 95% confidence interval) of percutaneous coronary intervention (BB 2.8, 2.2 to 3.5; LAN 2.1 1.7 to 2.6) and coronary artery bypass graft (BB 2.9, 2.0 to 4.1; LAN 2.3, 1.6 to 3.4) within 1 year of treatment initiation compared with those on ranolazine.9 For those on CCBs, the odds of coronary artery bypass graft were comparable (1.3, 0.9 to 2.0) whereas the odds of percutaneous coronary intervention (1.5, 1.2 to 1.9) were significantly higher compared with those on ranolazine.

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    Real-world data has also shown that ranolazine is associated with decreased resource utilization and revascularization in patients with and without diabetes. Page and colleagues used US claims data to conduct a retrospective, quasi-experimental, propensity-matched comparison of patients with chronic stable angina (n = 8008) receiving ranolazine, calcium channel blockers, beta-blockers and long-acting nitrates [27]. Patients on beta-blockers and nitrates had higher rates of all-cause (adjusted incidence rate ratio [aIRR] from 1.16 to 1.32 and 1.10 to 1.33, respectively) and cardiovascular-related healthcare use (aIRR from 1.18 to 1.35 and 1.16 to 1.56, respectively); including outpatient and emergency room visits, inpatient admissions, and length of inpatient stay compared to ranolazine.

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    To our knowledge, no randomized controlled trials have directly compared ranolazine with long-acting nitrates in chronic stable angina. However, the results from Page et al offer some support for lower rates of revascularization and utilization outcomes among ranolazine users compared with long-acting nitrate users,13 although lower rates of healthcare utilization were also observed when comparing ranolazine users to β blocker and calcium channel blocker users. The 2012 Stable Ischemic Heart Disease guidelines recommend a β blocker as initial antianginal therapy in patients with Stable Ischemic Heart Disease,2 and that calcium channel blockers, long-acting nitrates, and ranolazine are all acceptable add-on or replacement therapies in patients who are unsuccessful, intolerant, or have contraindications to β blockers.

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Funding: The present study was supported by a grant from Gilead Sciences, Foster City, California.

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