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Published on: May 28, 2019
Ranolazine Therapy Reduces Non-ST-Segment-Elevation Myocardial Infarction and Unstable Angina in Coronary Disease
Gary L Murray1, Joseph Colombo2
1Director of Cardiac Research, The Heart and Vascular Institute, Germantown, Tennessee.
Insights
Ranolazine (RAN) improved autonomic function in coronary disease (CD) patients, reducing major adverse cardiac events (MACE). This suggests RAN offers cardioprotection beyond angina relief by enhancing parasympathetic tone.
Area of Science:
- Cardiology
- Autonomic Neuroscience
Background:
- High sympathetic tone and cardiac autonomic neuropathy (CAN) are linked to major adverse cardiac events (MACE).
- Ranolazine (RAN) has demonstrated potential in improving autonomic function.
Purpose of the Study:
- To assess the impact of ranolazine on autonomic function and MACE in coronary disease (CD) patients.
- To explore ranolazine's potential cardioprotective mechanisms beyond its anti-anginal effects.
Main Methods:
- A prospective study comparing 51 anginal CD patients treated with ranolazine (RANCD) to 54 non-anginal CD patients on baseline therapy (NORANCD).
- Semi-annual autonomic function tests and yearly myocardial perfusion imaging (MPI) were conducted over a mean of 6.1 years.
Main Results:
- Ranolazine-treated patients experienced fewer MACE (29% vs. 46%, p=0.0105).
- Abnormal autonomic function measures were more prevalent in patients with MACE.
- Lower sympathovagal balance (indicating higher parasympathetic tone) was observed in the RANCD group.
Conclusions:
- Ranolazine improves autonomic function, specifically increasing parasympathetic tone, which may contribute to its cardioprotective effects in coronary disease.
- RAN may offer a novel mechanism for improving cardiovascular outcomes by modulating autonomic balance.
Abstract:
High sympathetic tone and cardiac autonomic neuropathy (CAN) are associated with major adverse cardiac events (MACE). We have shown ranolazine (RAN) improves autonomic function. RAN was introduced to 51 successive anginal CD patients (RANCD). A control group of 54 successive nonanginal CD patients (NORANCD) continued baseline therapy. Mean study duration was 6.1 years, which included semi-annual autonomic function measures (ANX 3.0, ANSAR Medical Technologies, Inc., Philadelphia, PA) and yearly myocardial perfusion SPECT studies (MPI). MACE were experienced by 29% RANCD patients versus 46% NORANCD patients (p = 0.0105). The patients from both groups with abnormal parasympathetic and sympathetic (P&S) measures and MACE totaled 52 of those patients with MACE versus 17% of those patients without MACE (p = 0.0274). Abnormal MPI was demonstrated in 35% of those with abnormal (P&S) measures and MACE versus 12% without MACE. Sympathovagal balance (SB) was lower, indicating higher, relative parasympathetic tone (known to be cardioprotective) in the RANCD group. Acute coronary syndromes occurred 4.5 times as often in NORANCD patients. High SB occur more frequently than abnormal MPI in CD patients experiencing MACE. In addition to increased myocardial blood flow as its proposed mechanism of angina relief, RAN improves P&S measures, a potentially new mechanism whereby RAN improves outcomes.
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