Effects of Spironolactone During an Angiotensin II Receptor Blocker Treatment on the Left Ventricular Mass Reduction in Hypertensive Patients With Concentric Left Ventricular Hypertrophy

Ikuo Taniguchi, Makoto Kawai, Taro Date, Satoru Yoshida, Shingo Seki, Masayuki Taniguchi, Mitsuyuki Shimizu, Seibu Mochizuki
2006 Circulation Journal  
he blockade of the renin -angiotensin -aldosterone system has beneficial effects on cardiovascular remodeling. Many patients with hypertension, heart failure, and post-myocardial infarction have been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) to prevent cardiovascular events. 1-3 ARB blocks the action of angiotensin II (Ang II) and subsequently suppresses the secretion of aldosterone from the adrenal gland, and prevent the development
more » ... t the development of cardiovascular remodeling. Recently, aldosterone has been recognized to play a crucial role in the pathophysiology of myocardial remodeling in cardiovascular diseases. 4-6 It has been reported that an aldosterone breakthrough during ACE inhibitor or ARB treatment might reverse some of the beneficial effects on cardiovascular remodeling. 7, 8 We reported that an ARB treatment is less effective for preventing cardiac fibrosis in left ventricular (LV) hypertrophy in renovascular hypertensive rats than an ACE inhibitor, despite similar changes in blood pressure (BP). 9 It is not clear whether ACE inhibitors or ARB sufficiently inhibit the action of intrinsic aldosterone, which is involved in the development of cardiac remodeling. However, LV hypertrophy is an independent risk factor in cardiovascular events. 10 The regression of LV hypertrophy is an important target to treat hypertension. A randomized clinical study, The Randomized Aldactone Evaluation Study (RALES), indicated that an aldosterone blocker, spironolactone (SPRL), reduced the risk of both morbidity and death in the patients with severe heart failure. 11 The combined treatment of ACE inhibitor and SPRL has been reported to have beneficial effects on LV remodeling in hypertensive patients. 12 Also, we have reported that ARB monotherapy reduced the plasma aldosterone concentration (PAC) levels for the first 6 months; however, some patients experienced a rise in the PAC levels during the late phase of treatment. 13 We studied the additional effects of SPRL during an ARB treatment and conventional treatments on LV remodeling to strongly inhibit the action of aldosterone in patients with essential hypertension. Background Angiotensin II receptor blockers (ARB) are now commonly used to treat hypertension because of their beneficial effects on cardiovascular remodeling. However, ARB treatment can not inhibit the left ventricular (LV) remodeling sufficiently, which may be related with aldosterone secretion. To inhibit the action of aldosterone during ARB treatment, the additional effects of an aldosterone blocker and spironolactone (SPRL) on LV hypertrophy in patients with essential hypertension was studied. Methods and Results The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group). Seventy patients who underwent echocardiography every 6 months were analyzed and were also classified into 4 subgroups of LV geometric pattern according to the LV mass index (LVMI) and the relative wall thickness (RWT). The ARB treatment and the addition of SPRL significantly reduced the blood pressure, however, both treatments did not affect the LV geometry in both groups. The ARB treatment in the subgroups of concentric LV remodeling (RWT ≥0.45 and LVMI <125) and concentric LV hypertrophy (RWT ≥0.45 and LVMI ≥125) significantly reduced RWT. However, ARB treatment in all subgroups did not affect LVMI. The addition of SPRL only in the concentric LV hypertrophy subgroup significantly reduced the LVMI, despite similar changes in blood pressure. Conclusions These results indicated that the addition of SPRL treatment during the ARB treatment and conventional treatments is clinically useful to reduce the LVMI in hypertensive patients with concentric LV hypertrophy; however, does not improve the eccentric LV hypertrophy. (Circ J 2006; 70: 995 -1000)
doi:10.1253/circj.70.995 pmid:16864931 fatcat:dfms2mtzhrbf3f7vgigocd5yce