Trimetazidine new formulation redefining angina control in daily practice

Chronic coronary syndrome (CCS) remains a leading cause of death and disability worldwide. The dual goals of CCS management is to prevent future cardiac events, such as myocardial infarction and death, and to reduce ischaemia and relieve angina symptoms, says Prof Peter Yan, consultant cardiologist and medical director, Peter Yan Cardiology Clinic, Gleneagles Medical Centre, Singapore, during a Servier-sponsored virtual symposium.

“Primary strategies for the prevention of cardiovascular events include lifestyle modification and control of risk factors through the use of disease-modifying drugs,” he added. Guidelines have also put emphasis on the improvement of quality of life through symptomatic treatment with traditional first-line antianginal agents and anti-ischaemic metabolic drugs, such as trimetazidine (Vastarel® XR 80 mg) as an adjunct therapy for angina.

Optimizing myocardial energetics with trimetazidine

“Trimetazidine not only inhibits fatty acid oxidation (FAO), it also promotes glucose oxidation (GO) during peak exertion, which increases ATP production, thereby limiting myocardial ischaemia and controlling angina,” said Prof Derek Hausenloy, senior consultant, Cardiology, National Heart Centre Singapore. “The haemodynamically neutral side effect profile of trimetazidine also facilitate its clinical use as a second-line antianginal agent.”

Trimetazidine for stable angina 

Trimetazidine is indicated as an add-on therapy for the symptomatic treatment of stable angina that is inadequately controlled by first-line antianginal therapies or to patients intolerant to such therapy.

Studies have demonstrated the benefits of trimetazidine in CCS patients with angina. In a meta-analysis of 13 studies in 1,328 patients, trimetazidine reduced angina attacks and nitroglycerin use, increased time to 1mm ST-segment depression on a treadmill, and increased exercise duration at peak exercise. [Int J Cardiol 2014;177:780-785]

Trimetazidine in diabetic patients with angina

In patients with diabetes and angina, GO is further reduced due to insulin sensitivity – and the effect of trimetazidine on FAO inhibition may be more prominent, said Hausenloy. “Trimetazidine reduced angina, improved heart function, reduced myocardial injury in PCI*, as well as reduced infarct size when used as an adjunct therapy to primary PCI.”

Trimetazidine may be cardioprotective during PCI, CABG**

Pre-treatment with trimetazidine may also reduce the extent and magnitude of procedural myocardial injury associated with myocardial revascularization in patients undergoing PCI or CABG, added Hausenloy.

Trimetazidine in modern-day angina patients

When assessed in a real-world setting, trimetazidine modified-release 80 mg, given once daily for 3 months, in addition to standard antianginal therapy, reduced the frequency of anginal attacks, reported Dr Melvin Tan, consultant and interventional cardiologist, Melvin Tan Cardiology Practice, Mount Elizabeth Novena Specialist Centre, Singapore. The study included 3,066 patients with persistent symptoms despite therapy. [Adv Ther 2018; 35:1368-1377]

“There was a 52 percent reduction in the number of angina attacks/week after only 1 month of treatment with trimetazidine, and an 81 percent reduction after 3 months of its use,” he shared.

Another measure of an antianginal drug’s efficacy is the reduction in the use of short-acting nitrates (SAN), according to Tan. “After 1-month of treatment, there was a 56 percent reduction in the number of SAN taken by the patients per week and an 84 percent reduction after 3 months.”

Importantly, more patients stayed with trimetazidine without limitation. There were improvements in the Canadian Cardiovascular Society (CCS) grading scale, which is a measure of angina severity. “At 3 months, 68 percent of the patients had mild angina (CCS I), a major improvement from 17 percent at baseline and 41 percent at 1 month,” said Tan. “There were also fewer patients with CCS II and CCS III angina at 3 months vs baseline and after 1 month of treatment.”

In the sub-analysis of the trial, initiating trimetazidine 80 mg OD or switching to trimetazidine 80 mg OD (after treatment with trimetazidine 20 mg TID or trimetazidine 35 mg BID) both decreased the frequency of angina attacks. Nitrates consumption and physical activity also significantly improved in both the initiation and switch groups. [Cardiol Ther 2019;8:69-78]

Takeaway message

Trimetazidine, now available in Singapore in an advanced formulation, has been proven to reduce the frequency and severity of anginal episodes and improve exercise tolerance in patients with angina. Early and accurate diagnosis of often occult coronary artery disease is essential in preventing potentially fatal cardiovascular events in these patients, Tan concluded.