1.
[Clinical effect of various trimetazidine formulations in chronic coronary syndrome].
Nagy, VL, Herold, Z
Orvosi hetilap. 2020;(16):611-622
Abstract
Introduction: Trimetazidine is a metabolic agent of proven efficacy in the management of chronic coronary syndromes. According to guidelines, trimetazidine should be considered as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects whose symptoms are not adequately controlled by beta-blockers, calcium channel blockers and/or long-acting nitrates. Aim: This meta-analysis aimed to evaluate the efficacy of different doses (3 × 20 mg, 2 × 35 mg, 1 × 80 mg) of trimetazidine formulations in stable angina pectoris. Primary outcomes consisted of clinical parameters: numbers of weekly angina attacks and nitroglycerin usage. Method: Articles were collected from PubMed, Cochrane Library and Cochrane Central Register of Controlled Trials databases for the period from 1967 to 30 September 2019. Statistical analysis was performed by standard meta-analysis methods. Results: A total of 31 randomized controlled and observational trials, consisting of 9856 participants (mean age: 59.6 years, men: 61.6%) were included. Trimetazidine treatment, compared to placebo, reduced the number of weekly angina attacks (mean difference: –1.84, 95% CI: –2.39 to –1.30; p<0.0001) and reduced weekly nitroglycerin consumption (–1.65, 95% CI: –2.17 to –1.14; p<0.0001) in randomized trials. Trimetazidine treatment reduced the number of weekly angina attacks (–3.73, 95% CI: –4.53 to –2.92; p<0.0001) and nitroglycerin consumption (–3.23, 95% CI: –4.23 to –2.24; p<0.0001) in observational studies. No difference in angina reduction and nitroglycerin intake was observed between the three treatment doses (p = 0.57 and p = 0.48, respectively). Further results: the two primary variables decreased from visit to visit, higher enrollment angina rates and lower doses of trimetazidine were observed in shorter studies. Patients in shorter trials were younger than subjects in the longer ones. In shorter studies, the initial needs for nitroglycerin consumption and the following reduction were greater than those with longer duration. Conclusions: Regardless of dosage, trimetazidine has a favorable clinical effect in stable angina. New finding is that younger patients with more severe conditions show the most clinical benefit from treatment with trimetazidine. Orv Hetil. 2020; 161(16): 611–622.
2.
[Trimetazidine and cardioprotection during ischemia-reperfusion].
Barsotti, A, Di Napoli, P
Italian heart journal : official journal of the Italian Federation of Cardiology. 2004;:29S-36S
Abstract
Although early reperfusion of ischemic myocardium is now considered to be the only intervention able to restore the various cellular functions altered by ischemia and to prevent progression toward cell death of myocardial cells due to necrosis or apoptosis, reperfusion is accompanied by various manifestations grouped under the heading of reperfusion damage or reperfusion syndrome. Functional recovery is therefore not immediate, but usually appears after a certain delay following a period of contractile dysfunction (myocardial stunning) lasting for several hours or even days after the start of reperfusion. The cellular mechanisms underlying the reperfusion damage may involve cellular calcium overload, over-production of oxygen-derived free radicals, cellular acidosis, inflammatory reaction, and microcirculatory dysfunction. Numerous pharmacological studies have been conducted to limit such reperfusion injury and, consequently, prevent stunning and/or reperfusion-induced arrhythmias. A number of experimental and clinical studies have demonstrated the beneficial effects of trimetazidine, a drug that inhibits the long-chain mitochondrial 3-ketoacyl coenzyme A thiolase enzyme in the myocyte, resulting in a shift from fatty acid oxidation to glucose oxidation. This optimization of cardiac metabolism results in direct anti-ischemic effects, limiting calcium accumulation and acidosis, inflammation and oxygen free radical production, and improvement of coronary microcirculation following reperfusion. This agent appears to be particularly promising clinically in the treatment of reperfusion injury, for example in combination with reperfusion strategies during the acute phase of myocardial ischemia or infarction, or in the reduction of the pro-remodeling effects of ischemia in patients with chronic ischemic syndrome and left ventricular dysfunction.