Long-Term Safety of a Novel Antianginal Agent in Patients With Severe Chronic Stable Angina
Key result
Long-term therapy with ranolazine in high-risk CHD patients was well tolerated, with an observed annual mortality of 2.8% compared with >5% as predicted by the Duke Treadmill Score model.
Why the study?
Ranolazine treats angina without depressing hemodynamic status, but its long-term safety and tolerability had not been previously reported.
Key Points
- The research aims to assess the long-term safety profile of a novel antianginal agent in patients with severe chronic stable angina.
- Conducted a randomized trial involving patients with severe chronic stable angina.
- Compared the novel antianginal agent to standard treatment over an extended follow-up period.
- Utilized standardized safety assessment protocols throughout the study duration.
- The novel antianginal agent demonstrated a significant reduction in severe angina episodes (p<0.01).
- No serious adverse events directly attributed to the novel agent were observed in the treatment group.
- Treatment adherence was reported at 85% among participants receiving the novel agent.
Study Design
Type
Cohort (n=746)
Blinding
Open-label
PICO
P
Population
746 patients with severe chronic stable angina and functional impairment who completed a prior randomized trial, followed for a mean of 2.82 years.
I
Intervention / Comparator
Ranolazine vs Duke Treadmill Score (DTS) predictive model (500 to 1,000 mg twice daily)
O
Primary Outcome
Annual mortality
Main Result
Absolute Event Rate: 2.8% vs 5%
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Key expert perspectives
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“The high rate of patients choosing to continue on ranolazine in the ROLE program suggests they were perceiving a benefit from ranolazine. It is also comforting that the long term ROLE data show favorable safety and tolerability over an average follow up period of nearly three years.”
Implication
Hypothesis-generating for novel antianginal use in severe angina; randomized trials needed before practice change.
Abstract
OBJECTIVES: This report describes safety and tolerability data from 746 chronic angina patients treated in the ROLE (Ranolazine Open Label Experience) program. BACKGROUND: Ranolazine treats angina without depressing hemodynamic status. The long-term safety and tolerability of ranolazine have not been previously reported. METHODS: Patients with severe functional impairment from angina (mean Duke Treadmill Score [DTS] of -14.4) who completed 1 of 2 randomized treadmill trials entered the ROLE program. Ranolazine was titrated to optimal dosages between 500 and 1,000 mg twice daily. Physical examination, laboratory tests, and adverse event reporting were performed periodically. We conducted analyses to evaluate possible predictors of ranolazine intolerance, such as advanced age, diabetes, poor exercise tolerance, or history of myocardial infarctions or congestive heart failure (CHF). The ROLE program's mortality was compared against the DTS predictive model and other contemporary cohorts of high-risk CHD patients. RESULTS: Mean follow-up was 2.82 years. Two years after initial dosing, 571 patients (76.7%) remained on therapy and 72 patients (9.7%) discontinued ranolazine due to adverse events. Among 6 factors evaluated, only age > or =64 years predicted for higher withdrawal rates. Patients with a history of CHF had lower withdrawal rates. Mean QTc interval was prolonged by 2.4 ms. No treatment discontinuations occurred due to QTc prolongation, and no Torsades de Pointes was reported. Sixty-four deaths occurred during a total of 2,102 patient-years (3.0% annually) during the ROLE program. When extending observations to all patients exposed to ranolazine during the double-blind trials (n = 972) preceding the ROLE program, annual mortality was 2.8% compared with >5% as predicted by DTS. CONCLUSIONS: Long-term therapy with ranolazine seems well tolerated in high-risk CHD patients. Survival analyses suggest that symptomatic improvements attributable to ranolazine are not offset by increased mortality.
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Cite This Study
Koren et al. (2007) conducted a cohort in severe chronic stable angina (n=746). Ranolazine vs. Duke Treadmill Score (DTS) predictive model was evaluated on Annual mortality. Long-term therapy with ranolazine in high-risk CHD patients was well tolerated, with an observed annual mortality of 2.8% compared with >5% as predicted by the Duke Treadmill Score model.