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J Cardiovasc Ultrasound. 2010 September; 18(3): 84–85.
Published online 2010 September 30. doi:  10.4250/jcu.2010.18.3.84
PMCID: PMC2955337

The Effect of High-Dose Valsartan on Left Ventricular Function Following Primary Percutaneous Coronary Intervention

Tae-Ho Park, MD, PhDcorresponding author

REFER TO THE PAGE 77-83

The study by Kim et al.1) revealed that while improvement of regional function by valsartan was more effective in the high-dose (160 or 320 mg) valsartan group, compared with the low-dose group, high-dose valsartan did not have effects on left ventricular ejection fraction (LVEF) and lift ventriculal (LV) size.

Angiotensin-receptor blockers (ARBs) should be used in post-ST-segment elevation myocardial infarction (STEMI) patients with evidence of LV dysfunction who are intolerant to angiotensin-converting enzyme (ACE) inhibitors.2) ARBs reduce mortality and morbidity rates in patients with heart failure (HF) and reduced LVEF. Investigators of the Val-HeFT3) and CHARM4) trials reported that high doses of ARBs improved clinical outcomes. Recently, the HEAAL study5) demonstrated that high-dose (losartan 150 mg) is superior to low-dose ARB (losartan 50 mg) in patients with HF and reduced LVEF. In contrast to the latter ARB trials, the VALIANT study6) focused on patients with HF after acute myocardial infarction (MI) and demonstrated that a high-dose ARB (valsartan 320 mg) was not inferior to an ACE inhibitor (captopril 150 mg). However, the VALIANT study did not evaluate dose-dependent clinical outcomes.

The study by Kim et al.1) is helpful to understand changes in dose-dependent LV remodeling. However, this study has several limitations in terms of dose-dependent echocardiographic changes. First, the study population size was too small to compare LVEF and LV size between two groups. In the VALIANT Echo study, the small improvement in LVEF was observed in 610 patients. Second, baseline LVEF was too high (mean EF 52.7 ± 8.1%) to evaluate LV remodeling, compared to other remodeling studies such as the VALIANT (EF ≤ 35%) and HEAAL (EF ≤ 40%) studies. Third, the results do not definitively answer the question of why improvement of segmental wall motion was better in the high-dose than in the low-dose group. If additional information, such as myocardial microcirculation by myocardial contrast echocardiography and drugs affecting LV function were provided, the results would be more convincing.

Valsartan (Diovan) is an oral angiotensin II-receptor antagonist with specificity for the angiotensin II type 1 receptor subtype. It has been shown to attenuate the progression of chronic HF and to reduce mortality in patients with myocardial infarction. Although based on clinical trials high-dose ARB (Valsartan 160 mg BID) is recommended for the improvement of LV function in heart failure, low-dose ARB is preferred in clinical practice in patients with HF. The ARB dose may vary according to race and personal preferences. In the VALIANT study, discontinuation of valsartan (160 mg BID) was observed in 1,675 (34%) patients. However, in the study by Kim et al.1), discontinuation of high-dose valsartan was seen in 43 (68%) patients.

By comparing two groups prospectively after randomization, the present study concludes that high-dose valsartan is more effective than low-dose valsartan in improving segmental wall motion. Even though this is a small study to compare dose-dependent echocardiographic LV remodeling, it reveals the benefit of high-dose treatment, which may allow recommendation of high-dose valsartan even in post-STEMI cases.

Footnotes

Editorials published in the Journal of Cardiovascular Ultrasound do not necessarily represent the views of JCU or the Korean Society of Echocardiography.

References

1. Kim SS, Jeon HK, Cho GM, Lee JH, Kim SJ, Park MY, Lee SJ, Shim BJ, Lee DH, Shin WS, Lee JM, Youn HJ. Evaluation of cardiac function by transthoracic echocardiography in subjects with ST-segment elevation myocardial infarction following primary percutaneous coronary intervention according to valsartan dose: the valsartan one center trial. J Cardiovasc Ultrasound. 2010;18:77–83. [PMC free article] [PubMed]
2. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC., Jr American College of Cardiology; American Heart Association; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction) J Am Coll Cardiol. 2004;44:671–719. [PubMed]
3. Cohn JN, Tognoni G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–1675. [PubMed]
4. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S. CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362:759–766. [PubMed]
5. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, Riegger GA, Malbecq W, Smith RD, Guptha S, Poole-Wilson PA. HEAAL Investigators. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374:1840–1848. [PubMed]
6. Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM. Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349:1893–1906. [PubMed]

Articles from Journal of Cardiovascular Ultrasound are provided here courtesy of Korean Society of Echocardiography