OPTIMAL MEDICAL TREATMENT OF CHRONIC CORONARY SYNDROMES (CCS): FROM THE “OLD MODEL” TO A NEW COMBINATION APPROACH

By Dr Zurina Salas (Cardiologist, Bahamas)

Optimal medical therapy is the cornerstone of treatment with CCS with the ISCHEMIA trial1 showing similar outcomes using OMT with or without an initial invasive approach. Treatment aims at cardiovascular risk reduction and symptom relief and better quality of life2.

Because fewer than 33% of patients with angina receive OMT before revascularization, the modern approach is optimization of medical therapy that should last 3-6 months before considering revascularization2.

What constitute as optimum approach to pharmacotherapy? Lifestyle advice such as cessation of smoking and exercise are paramount along with initiation of medications that control CV risk factors at diagnosis2. Antiplatelet therapy, the low dose combination of rivaroxaban to aspirin, lipid lowering agents, ACEi and SGLT2 inhibitors reduce CV events and stroke in high-risk patients. The CCS 2019 guidelines acknowledge the inconclusive data on combination therapy with beta blocker and calcium channel blocker2.

They also recommend initiation of antianginal therapy for 1-2 months with uptitration to a minimum of 2 agents at adequate doses with persistent angina. Invasive strategy with coronary revascularization is reserved for persistent angina after 3-6 months of OMT.

Angina pectoris has a considerable impact on a patient’s quality of life if not satisfactorily managed. The CLARIFY study3 showed that angina remains a burden in half of symptomatic patients despite current treatment strategies which are largely based on hemodynamic anti-anginal agents (beta blocker, calcium channel blockers, long-acting nitrates, ivabradine) and revascularization.

The mechanism of angina is multiple and often overlap hence treatment with only conventional hemodynamic drugs is not always appropriate4. For example, long-acting nitrates can be ineffective or have detrimental effects in microvascular dysfunction5. Of the multiple factorial origin of angina, the myocardial cell is the final central element4.

Trimetazidine (TMZ) differs from other antianginal agents in that it acts directly at the level of the myocardial cell. Add-on TMZ thus represents an opportunity to optimize antianginal treatment at a metabolic cellular level6.

There is clinical evidence from real world studies (ODA Trial) showing that TMZ 80 mg OD7, in association with other antianginal therapy, effectively reduces 80% of angina attacks, from 4.7 per week to 0.9 per week, short-acting nitrates consumption and improves physical activity. A 97% adherence to antianginal therapy was observed both in patients initiating TMZ treatment and those switching from a bid or tid formulation.

There is also evidence on the benefit of a modern approach with early combination of metabolic and hemodynamic approaches to OMT as shown by the MODUS-VIVENDI study8 on the efficacy of Trimetazidine 80 mg OD in real world CCS patients. At visit 1, the mean number of angina attacks per week was 6.2 despite hemodynamic antianginal therapy including maximally tolerated bisoprolol dosage. Following the addition of TMZ 80 OD, this decreased to 3.4 attacks per week at month 2, and 1.6 at month 3 (P < 0.05 at V2 and V3), with concomitant reductions in short-acting nitrate use (P < 0.05). Subgroup analyses showed significant improvements in QoL whether patients were treated with maximally tolerated bisoprolol and TMZ 80 OD alone, or maximally tolerated bisoprolol and TMZ 80 OD on top of other antianginal therapies. In conclusion, TMZ 80 OD appears as an optimal option from the beginning in combination with a BB in order to reduce angina attacks, improve exercise capacity and QoL7,8. Also, to attain a high level of OMT goal, adherence is key! TMZ 80 OD has also demonstrated improvement in adherence7.

1. International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches (ISCHEMIA): Judith S. Hochman, MD On behalf of the ISCHEMIA Research Group
2. Knuuti J et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41³:407-77
3. Mesnier et al. International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational Volume 144, Issue 7, 17 August 2021; Pages 512-523.
4. KASKI et al. Reappraisal of ischemic heart disease. Circulation. 2018;138(14):1463-80
5. Tarkin JM, Kaski JC. European Cardiology Review. 2018, 13¹. 23-8.
6. Fragasso et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine adenosine triphosphate ratio in patients with heart failure, European Heart Journal (2006) 27, 942
7. GLEZER et al; ODA investigators. Anti-anginal effectiveness and tolerability of trimetazidine modified release 80 mg once daily in stable angina patients in real-world practice. Adv Ther. 2018 Sep;35⁹:1368-1377
8. LOPATIN & PETROVA; MODUS VIVENDI investigators. Effectiveness and tolerability of trimetazidine 80 mg once daily in patients with stable angina uncontrolled with bisoprolol-based therapy: The Modus Vivendi Observational Study. Cardiol Ther. 2022 Mar;11¹:93-111

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