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Microvascular ischemia in patients with successful percutaneous coronary intervention: effects of ranolazine and
M Golino1, F R Spera, L Manfredonia
1Institute of Cardiology, Catholic University of the Sacred Heart, A. Gemelli Foundation, Rome, Italy. Gaetanoantonio.lanza@unicatt.it.
Insights
Ranolazine improved exercise stress test outcomes in patients with persistent myocardial ischemia after PCI, unlike ISMN. This benefit occurred without affecting coronary microvascular or diastolic function, suggesting a novel therapeutic mechanism.
Area of Science:
- Cardiology
- Interventional Cardiology
- Pharmacology
Background:
- A significant portion of patients experience persistent myocardial ischemia (MI) during exercise stress tests (EST) even after successful percutaneous coronary interventions (PCI).
- Coronary microvascular dysfunction is implicated as a primary contributor to ongoing EST-induced MI in these individuals.
Purpose of the Study:
- To evaluate the efficacy of ranolazine versus isosorbide-5-mononitrate (ISMN) in patients with persistent EST-induced MI post-PCI.
- To assess the impact of these drugs on coronary microvascular function and diastolic left ventricular function.
Main Methods:
- A single-blind, randomized crossover study involving 15 patients with recent PCI and persistent EST-induced MI.
- Patients received either ranolazine (375 mg bid) or ISMN (20 mg bid) for 3 weeks, with assessments at baseline and after each treatment period.
- Evaluations included clinical assessment, symptom-limited EST, echocardiography, and coronary microvascular function tests (CFR-ADO, CFR-CPT).
Main Results:
- Ranolazine significantly increased the time to 1 mm ST-segment depression during EST compared to both baseline and ISMN (404±116 s vs. 317±98 s and 322±70 s, p<0.01).
- No significant differences were observed in coronary microvascular function or diastolic left ventricular function between ranolazine, ISMN, and baseline.
Conclusions:
- Ranolazine demonstrated an improvement in exercise tolerance, indicated by a longer time to ischemia during EST, in patients with persistent MI post-PCI.
- This beneficial effect of ranolazine was independent of improvements in coronary microvascular or diastolic function, suggesting a distinct mechanism of action.
Objective:
About one-third of patients undergoing percutaneous coronary interventions (PCIs) for flow-limiting coronary stenosis continue to develop signs of myocardial ischemia (MI) during exercise stress test [EST], despite successful coronary revascularization. Coronary microvascular dysfunction is a likely major cause of the persistence of EST-induced MI in these patients.
Patients And Methods:
We studied 15 patients (14 men, age 67±5 years) fulfilling the following strict inclusion criteria: (1) recent PCI (<6 months), with drug-eluting stent, of coronary artery stenoses for stable angina, with evidence of full success (no residual stenosis >20% in any vessel); (2) persistence of ST-segment depression induction during EST. After a basal investigation, patients received either ranolazine (375 mg bid) or isosorbide-5-mononitrate (ISMN, 20 mg bid) for 3 weeks in a single-blind, randomized crossover study. Clinical assessment, symptom-limited EST, echocardiographic color-Doppler, with tissue-Doppler examination, and coronary microvascular dilator response to adenosine (CFR-ADO) and cold pressor test (CFR-CPT), assessed by transthoracic echo-Doppler, were obtained at baseline and the end of the 3-week therapy with each drug.
Results:
Compared to both baseline and ISMN, ranolazine showed a longer time to 1 mm ST-segment depression (404±116 s vs. 317±98 and 322±70 s, respectively; p<0.01). No differences were observed in coronary microvascular function and diastolic left ventricular function between the 2 drugs and compared to baseline.
Conclusions:
Our data show that ranolazine, but not ISMN, improved time to ischemia during EST. This effect, however, was independent of any effects on coronary microvascular and diastolic function.
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