Aims: Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk-benefit profile of different doses have not been fully identified.
Methods and results: In this multicentre trial, 495 Korean patients with acute ST segment elevation MI and subnormal left ventricular (LV) ejection fraction (<50%) were randomly allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to 320 mg/day, n = 333) or low-dose valsartan (80 mg/day, n = 162) treatment. The primary objective was to assess the changes in echocardiographic parameters of LV remodelling from baseline to 12 months after discharge. After treatment, end-diastolic LV volume (LVEDV) decreased significantly in the low-dose group, but the difference in LVEDV changes was insignificant between the maximal-tolerated-dose and low-dose groups. End-systolic LV volume decreased significantly in both groups, to a similar degree between groups. LV ejection fraction rose significantly in both study groups, to a similar degree. Changes in plasma levels of neurohormones were also comparable between the two groups. Drug-related adverse effects occurred more frequently in the maximal-tolerated-dose group than in the low-dose group (7.96 vs. 0.69%, P < 0.001).
Conclusions: In the present study, treatment with the maximal tolerated dose of valsartan did not exhibit a superior effect on post-MI LV remodelling compared with low-dose treatment and was associated with a greater frequency of adverse effect in Korean patients. Further study with a sufficient number of cases and statistical power is warranted to verify the findings of the present study.
Keywords: Dose; Myocardial infarction; Valsartan; Ventricular remodelling.
© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.