Trimetazidine may be a new additional therapy to improve symptoms and cardiac function for patients after proceeding with surgical valve replacement

Abstract

Background: After successful surgery for valvular heart disease, symptoms and cardiac function are in general greatly improve. Nevertheless, left ventricle dysfunction and heart failure symptoms may persist and worsen postoperatively. We hypothesized that the metabolically acting agent trimetazidine would help improve symptoms and cardiac function after valve replacement. Methods: In a randomized, open-label, case-control 1-year study, trimetazidine (35 mg twice daily) was added to optimal standard therapy (vitamin K antagonists ACEIs/ARBs, beta-blockers, diuretics, statins, and digoxin) 2-4 weeks after conventional aortic/mitral valve replacement. Efficacy endpoints included changes from preoperative baseline in 6-min walk distance (6-MWD), New York Heart Association (NYHA) functional class, hemodynamic parameters, heart failure hospitalizations, and all-cause mortality. Results: 120 patients [mean (SE) age 53.2 (2.1) years, 72 males (60%), 48 females (40%)] with mechanical prosthesis of aortic (n=64) and mitral (n=56) valve [48 due to degenerative (40%), 42 rheumatic (35%), 12 myxomatous (10%), 10 congenital valve diseases (8.3%) and 8 infectious endocarditis (6.7%); 65% NYHA class III, 35% NYHA class II; 20% concomitant CABG; median (IQR) 6-MWD 329 (162-420) m; mean (SE) left ventricular ejection fraction (LVEF) 59.6 (2.8)%] were randomized. There were no significant differences between trimetazidine and control group at baseline. At month 12, patients receiving trimetazidine (n=60) had a mean increase in 6-MWD of 156 m (p<0.0001); control patients (n=60) had a mean 6-MWD increase of 121 m (p=0.0005), with a control-adjusted difference of +35 m (p=0.041). NYHA status improved by two classes in 40% of trimetazidine versus 21.7% of controls (p=0.035), by one class in 60% versus 78.3% (p=0.035). Trimetazidine delayed the time to clinical worsening (p=0.0202) and reduced the heart failure admissions (p=0.0045). Improvements were noted in control-adjusted changes in postoperative heart remodelling, e.g. in mean LVEF (+3.8%; p=0.003), left ventricular end-diastolic diameter (-5.6 mm; p=0.001), and end-systolic diameter (-3.7 mm; p=0.004). Combination therapy with trimetazidine was well tolerated. No a patient died in the trimetazidine group, as compared with one patient in the control group (p=0.89). Conclusions: Long-term trimetazidine therapy for patients with mechanical aortic/mitral valve prostheses improves symptom status and cardiac function. This study supports the hypothesis of clinical benefits from continued metabolic trimetazidine in surgically corrected valvular heart disease.