Key result
Addition of ivabradine to beta-blocker therapy significantly increased the proportion of patients who were angina-free at 16 weeks compared to beta-blocker uptitration (50.6% vs. 34.2%, p<0.001).
Why the study?
Does adding ivabradine to beta-blockers improve angina control and reduce heart rate compared to beta-blocker uptitration in patients with stable angina?
RCT (n=1,104)
Open-label
4:1 ratio (consecutive patients)
Yes
Does adding ivabradine to beta-blockers improve angina control and reduce heart rate compared to beta-blocker uptitration in patients with stable angina?
In patients with stable angina on submaximal beta-blockers, adding ivabradine provides superior angina relief and is better tolerated than uptitrating the beta-blocker dose.
Supports adding ivabradine over beta-blocker uptitration for angina relief; extends RCT evidence on combination therapy in stable angina.
INTRODUCTION: Heart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina. METHODS: This multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio. RESULTS: At the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001). CONCLUSION: In patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration. TRIAL REGISTRATION: ISRCTN30654443.
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Глезер et al. (2018) conducted an RCT in Stable angina (n=1,104). Ivabradine + Beta-Blockers vs. Uptitration of beta-blockers to maximal tolerated dose was evaluated on Proportion of patients angina-free at week 16 (p=<0.001). Addition of ivabradine to beta-blocker therapy significantly increased the proportion of patients who were angina-free at 16 weeks compared to beta-blocker uptitration (50.6% vs. 34.2%, p<0.001).
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