By Michael H. Crawford, MD, Editor

SYNOPSIS: For patients with stable ischemic heart disease, adding either ranolazine or calcium channel blockers to nitrate or beta-blocker therapy reduced the incidence of subsequent revascularization and costs vs. beta-blocker or nitrate therapy alone or in combination.

SOURCES: Meyer N, Tran O, Hartsfield C, et al. Revascularization rates and associated costs in patients with stable ischemic heart disease initiating ranolazine versus traditional antianginals as add-on therapy. Am J Cardiol 2019;123:1602-1609.

Rasalingam R, Boden WE. Role of ranolazine in reducing angina, subsequent revascularization, and healthcare expenditures in stable ischemic heart disease. Am J Cardiol 2019;123:1729-1731.

In patients with documented stable ischemic heart disease (SIHD), if symptoms are not controlled by antianginal (AA) therapy, guidelines recommend considering coronary artery revascularization, which increases the cost of managing such patients. Meyer et al analyzed a large group of insured patients in the United States.

SIHD patients treated with beta-blockers, calcium channel blockers, nitrates, or ranolazine were identified. They were divided into four groups: ranolazine added to one to three other AAs, beta-blockers as second or third AA, calcium channel blockers added, or long-acting nitrate added. The authors assessed revascularization, hospitalizations for revascularization, hospital length of stay, and total healthcare costs. The groups were adjusted for differing clinical characteristics, such as age, sex, and comorbidities. From 2008 through June 2016, the authors identified 108,741 patients with SIHD on AAs (18% were on ranolazine, 21% beta-blockers, 24% calcium channel blockers, and 37% long-acting nitrates). At baseline, 85% of patients were taking one AA and 15% were taking two AAs.

During follow-up (12 months), revascularization rates were lowest for the ranolazine group (11%) compared to the beta-blocker (16%) group and the nitrate group (14%; P < 0.001 for both) and were similar to the calcium channel blocker group (10%). In addition, compared to the beta-blocker and nitrate groups, ranolazine-treated patients were less likely to be hospitalized and stayed fewer days if they were admitted (P < 0.001). Mean healthcare costs were higher for beta-blocker ($4,465) and nitrate ($3,609) subjects vs. ranolazine ($2,933) or calcium channel blocker ($2,753) subjects (P < 0.001). The authors concluded that for SIHD patients, ranolazine and calcium channel blocker therapy was associated with fewer revascularization procedures and lower healthcare costs than treatment with beta-blockers or long-acting nitrates.

COMMENTARY

This study was designed to show the superiority of ranolazine as the second-choice agent for treating angina in SIHD patients whose symptoms are not controlled by one of three standard therapies for angina; it did. However, Meyer et al also showed that ranolazine was no better than calcium channel blockers for this purpose, a point glazed over in this pharmaceutical company-sponsored study. This does not surprise me, as earlier studies with calcium channel blockers showed their superiority over beta-blockers and nitrates for controlling angina. This fact seems to have been lost on my younger colleagues. I am continually surprised by how few of them put their patients on calcium channel blockers for angina control. When asked why, younger physicians usually respond that they thought the calcium channel blockers were only used for hypertension. Granted, calcium channel blockers can produce adverse effects. Dihydropyridine calcium channel blockers can cause tachycardia — but are a good addition to beta-blockers for this reason. Non-dihydropyridine calcium channel blockers can precipitate heart failure in patients with left ventricular ejection fractions < 35% — but are good at controlling heart rate. One major advantage of ranolazine as a second-choice agent for angina is that it does not affect heart rate or blood pressure. All three standard agents can reduce blood pressure to unacceptable levels at higher doses. The other interesting point: the preponderance of SIHD patients with angina were treated with only one agent (almost always a beta-blocker). This may be because U.S. guidelines recommend using a beta-blocker first in a stepwise algorithm for pharmacologic therapy. There are no solid data supporting this recommendation, and it may be an extrapolation from beta-blocker use after myocardial infarction and for heart failure. This undertreatment may be fueled by the ready availability and relatively low risk of percutaneous revascularization (PCI). However, revascularization does not prevent myocardial infarction or extend life. If symptom relief is the goal, it makes sense to try optimal medical therapy that includes not only more than one AA but risk factor control and lifestyle alterations. This approach was quite effective in the COURAGE trial.1

There were limitations to the Meyer et al study. It was retrospective and based on administrative data. There is a lack of granularity in the data. For example, we do not know which calcium channel blockers the patients were taking, the doses of any drugs, or compliance. Also, administrative databases may misclassify outcomes compared to medical records review. Despite the study’s flaws, Meyer et al emphasized that angina control with optimal medical therapy (which should include a calcium channel blocker or ranolazine) is preferable from a cost perspective and perhaps for patient safety than proceeding to PCI on suboptimal therapy.

REFERENCE

  1. Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516.