Randomized Study of Angiotensin II Type 1 Receptor Blocker vs Dihydropiridine Calcium Antagonist for the Treatment of Paroxysmal Atrial Fibrillation in Patients With Hypertension  The J-RHYTHM II Study Design for the Investigation of Upstream Therapy for Atrial Fibrillation

Yamashita, Takeshi; Ogawa, Satoshi; Aizawa, Yoshifusa; Atarashi, Hirotsugu; Inoue, Hiroshi; Ohe, Tohru; Okumura, Ken; Ohtsu, Hiroshi; Kato, Takao; Kamakura, Shiro; Kumagai, Koji; Kurachi, Yoshihisa; Kodama, Itsuo; Koretsune, Yukihiro; Saikawa, Tetsunori; Sakurai, Minoru; Sugi, Kaoru; Nakaya, Haruaki; Hirai, Makoto; Hirayama, Atsushi; Fukuda, Masahiko; Mitamura, Hideo; Yamazaki, Tsutomu; Watanabe, Eiichi; Investigators, The J-RHYTHM II

doi:10.1253/circj.70.1318

Cited by 16 publications

(6 citation statements)

References 27 publications

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“…60 In Japan, the J-RHYTHM II study, a largescale clinical study to investigate whether ARBs are more effective in the treatment of AF in patients with hypertension, is currently ongoing. 156 In that study, hypertensive patients with paroxysmal AF were randomized to a group receiving candesartan, an ARB, or a group receiving amlodipine, a calcium blocker, and days of AF, incidence of chronic AF, incidence of cardiovascular events, and QOL will be compared after one year of treatment. It is expected that the results of the study will demonstrate which antihypertensive drug is preferable for hypertensive patients with AF.…”

Section: Upstream Treatmentmentioning

confidence: 99%

Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008) - Digest Version -

Group¹

2010

Circ J

123

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Section: Upstream Treatmentmentioning

confidence: 99%

Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008) - Digest Version -

Group¹

2010

Circ J

123

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“…78 The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II Study) compares the effect of candesartan versus amlodipine for treatment of paroxysmal AF in patients with hypertension. 79 The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) Study investigates the efficacy of telmisartan, ramipril and combination therapy with telmisartan plus ramipril for reducing cardiovascular events, including AF in high-risk patients with controlled blood pressure. This study will provide important data on the potential incremental benefit of ACEI, ARB or both in preventing AF, independent of blood pressure lowering.…”

Section: Clinical Implicationmentioning

confidence: 99%

Hypertension and cardiac arrhythmias: a review of the epidemiology, pathophysiology and clinical implications

Yiu

Tse

2008

J Hum Hypertens

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Hypertension is commonly associated with cardiac arrhythmias in patients with and without concomitant cardiovascular disease. Experimental and epidemiological studies have demonstrated potential links between hypertension and atrial and ventricular arrhythmias, although the underlying pathophysiological mechanism remains unclear. Nonetheless, the importance of hypertension as a cause of atrial and ventricular arrhythmias is not well recognized. In particular, the occurrence of left ventricular hypertrophy is a strong predictor for the development of AF, ventricular ectopy and sudden cardiac death. Recent prospective clinical trials reveal that antihypertensive therapy may delay or prevent the occurrence of cardiac arrhythmias and sudden cardiac death in patients with hypertension. Although antihypertensive agents that block the renin-angiotensin-aldosterone system appear to protect against cardiac arrhythmias, this needs to be confirmed by current ongoing clinical trials.

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“…Activation of AT1 receptor, which occurs in the atria with increased frequency in patients with AF, induces fibrosis, which promotes the occurrence of arrhythmia [24]. Several studies has shown that AT1 receptor antagonists could really decreased the rate of AF recurrences or prevent atrial structural remodeling, a contributing factor for the development of AF, in animal model or clinical trial [10,25–27].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of angiotensin converting enzyme II is associated with pacing‐induced sustained atrial fibrillation

et al. 2007

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Atrial fibrillation (AF), the most common cardiac arrhythmia, is frequently accompanied by atrial interstitial fibrosis. Angiotensin II (Ang II) dependent signaling pathways have been implicated in interstitial fibrosis during the development of AF. However, Ang II could be further degraded by angiotensin converting enzyme II (ACE2). We examined expression of ACE2 in the fibrillating atria of pigs and its involvement in fibrotic pathogenesis during AF. Nine adult pigs underwent continuous rapid atrial pacing to induce sustained AF and six pigs were sham controls (i.e., sinus rhythm; SR). In the histological examinations, extensive accumulation of extracellular matrix in the interstitial space of the atria, as evidenced by Masson's trichrome stain, were found in fibrillating atria. The relative amount of collagen type I in the atria with AF was significantly increased as compared with that in the SR. Local ACE activity in the fibrillating atria was also markedly higher than that in the SR subjects. ACE2 gene and protein expression in the AF subjects were significantly decreased compared with those in the SR subjects, whereas expression of mitogen-activated/ERK kinase 1/2 (MEK1/2), extracellular signal-regulated protein kinase 2 (ERK2), and activated ERK2 were significantly greater in the AF subjects. We propose that decreasing ACE2 expression during AF may affect the Ang II-dependent signaling pathway. In addition, our results suggest that atrial fibrosis in AF may be induced by antagonistic regulation between ACE and ACE2 expression.

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Randomized Study of Angiotensin II Type 1 Receptor Blocker vs Dihydropiridine Calcium Antagonist for the Treatment of Paroxysmal Atrial Fibrillation in Patients With Hypertension The J-RHYTHM II Study Design for the Investigation of Upstream Therapy for Atrial Fibrillation

Cited by 16 publications

References 27 publications

Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008) - Digest Version -

Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008) - Digest Version -

Hypertension and cardiac arrhythmias: a review of the epidemiology, pathophysiology and clinical implications

Downregulation of angiotensin converting enzyme II is associated with pacing‐induced sustained atrial fibrillation

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