Beta blockers may be considered for ongoing management in patients with symptomatic IST.170,172 See Online Data and 5. Beta blockers are modestly effective in lowering the heart rate and improving symptoms that are due to IST. In a small nonrandomized observational cohort, metoprolol succinate titrated to a target of 95 mg daily lowered the heart rate over 4 weeks from a baseline.172 In a small nonrandomized study comparing metoprolol with ivabradine, both agents reduced heart rate compared with baseline and improved exercise Although effectiveness of beta blockers is modest and hypotension may limit dose, the overall safety of beta blockers warrants their use for treatment of symptomatic patients. IIb C-LD 2. The combination of beta blockers and ivabradine may be considered for ongoing management in patients with IST.172 See Online Data and 5. Some patients with IST may have particularly refractory symptoms, and single-drug efficacy may be limited. In a small observational study, the addition of ivabradine (7.5 mg twice daily) to metoprolol succinate (95 mg daily) reduced the heart rate from baseline to a greater extent than did metoprolol alone.172 On combination therapy, symptoms related to IST were resolved in all patients, and the combined therapy was well tolerated. In the SHIFT and BEAUTIFUL studies, the majority of patients were taking the combination of ivabradine and a beta blocker, which was well tolerated.166,167 Nevertheless, patients who are considered for combination therapy should be monitored closely for the possibility of excess bradycardia. Ivabradine can cause phosphenes, an enhanced brightness in a portion of the visual field; this side effect was reported in 3% of patients taking the drug in the SHIFT trial.167 Table 6. 