The impact of a dose of the angiotensin receptor blocker valsartan on post-myocardial infarction ventricular remodelling

Abstract

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.

Figure 1

Flow chart of participants in the randomized controlled trial. Five hundred four patients were enrolled at 17 centres and assessed for eligibility. Of those enrolled, nine were excluded from randomization for screening failure. Four hundred ninety‐five patients were randomized, of which 333 were allocated to the maximal‐tolerated‐dose group and 162 patients were allocated to the low‐dose group.

Figure 2

Systolic and diastolic blood pressure in the two treatment groups over the course of the trial.

Figure 3

Effect of valsartan on left ventricular echocardiographic measurements. Changes in left ventricular end‐diastolic volume (A), end‐systolic volume (B), and ejection fraction (C) from baseline to 12 months after randomization in both groups.

Figure 4

Effect of valsartan on plasma neurohormones. Changes in plasma B‐type natriuretic peptide (A) and norepinephrine (B) from baseline to 12 months after randomization.