benazepril and Atrial-Fibrillation

Benazepril is a nonsulfhydryl ACE inhibitor with favorable pharmacodynamic and pharmacokinetic properties, well-established antihypertensive effects and a good tolerability profile. Recent clinical studies have demonstrated that patients treated with benazepril alone or in combination with hydrochlorothiazide or amlodipine may achieve beneficial renal outcomes that extend beyond blood pressure control. Furthermore, the recent Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed decreased cardiovascular morbidity and mortality with benazepril when administered as a cotreatment. An additional novel therapeutic area for benazepril is atrial fibrillation. Differences between combination therapies have implications for which patients may be best suited to particular interventions, and further studies are required to fully ascertain this potential.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Benzazepines; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Kidney; Practice Guidelines as Topic; Prodrugs; Societies, Medical

The aim of this study was to observe the clinical efficacy of fluvastatin combined with benazepril in the treatment of patients with atrial fibrillation (AF). A total of 92 patients with AF were randomly assigned to the case group (n=46), in which the patients were treated with fluvastatin (80mg) plus benazepril (10mg), or to the control group (n=46), in which the patients were treated with fluvastatin (80mg). The conversion rate of sinus rhythm was higher in the case group than in the control group (P<0.05). The case group had more treatment-effective patients than the control group, with fewer treatment-ineffective patients (P<0.05). The LVEDd, LVESd, LAD, and LVEF indexes in the case group were lower than in the control group after 6 months of treatment (all P<0.05). Levels of hs-CRP were also lower in patients in the case group than in patients in the control group after 1 month of treatment (P<0.05). After 12 months, renin and Ang II concentrations were lower in patients in the case group than in the control group (both P<0.05). Significant differences in IL-6 and TNF-α expression were found between the two groups after 1 month, 6 months, and 12 months of treatment (all P<0.05). Compared to patients in the control group, the levels of total cholesterol (TC), triglycerides, and LDL-C in the case group were lower after 6 and 12 months of treatment (all P<0.05), while the HDL level was higher (P<0.05). Treatment with fluvastatin combined with benazepril further increased the conversion rate of sinus rhythm and significantly improved the quality of life and prognosis of AF patients.

Topics: Angiotensin II; Atrial Fibrillation; Benzazepines; C-Reactive Protein; Case-Control Studies; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heart Function Tests; Humans; Indoles; Interleukin-6; Kidney; Liver; Male; Middle Aged; Prognosis; Renin; Treatment Outcome; Tumor Necrosis Factor-alpha

Previous studies reported that RAS inhibitors prevented atrial fibrillation by improving atrial electrical and structural remodeling. However, the effect of RAS inhibitors on the substrates of atrial fibrillation (AF) underlying hyperthyroid is unclear.. Forty rabbits were assigned to four groups: sham group, thyroxine group, benazepril group and irbesartan group (10 per group). The atrial effective refractory period (AERP) was measured. The physiologic rate adaptation and the AF vulnerability were evaluated. The real-time PCR, Western blot or fluorescent immunohistochemistry was performed to detect the expression of AF related Ca+, K+ channel and gap junction.. No significant difference was found in AERP among the thyroxine group, benazepril group and irbesartan group (75.13±5.41ms vs. 76.63±4.44ms, 79±4.95ms, P=0.28). However, benazepril or irbesartan could reduce AF vulnerability underlying hyperthyroid (75% vs. 37%, 44%, for thyroxine group, benazepril group and irbesartan group, respectively), and significantly improved physiologic rate adaptation of the AERP. Furthermore, both drugs significantly reduced L-Ca(2+) channel related subunits (α1C or α1D) and interstitial fibrosis (17.1±2.2% vs. 12.3±1.8, 11.7±1.2%, P<0.01, for thyroxine group, benazepril group and irbesartan group, respectively), increased lateral/polar connection of Cx43 (1.04±0.16 vs. 1.33±0.29,1.28±0.25, P<0.01, for thyroxine group, benazepril group and irbesartan group, respectively) and improved the abnormal distribution of gap junctions (Cx40, Cx43) underlying hyperthyroid.. Blockade of angiotensin II could improve abnormal atrial electrophysiological properties and further reduce AF vulnerability by extenuating ion channel, gap junction and structural remodeling in experimental thyrotoxic rabbits.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Fibrillation; Benzazepines; Biphenyl Compounds; Calcium Channels, L-Type; Connexins; Gap Junctions; Heart Atria; Heart Rate; Hyperthermia, Induced; Hyperthyroidism; Irbesartan; Male; Rabbits; Refractory Period, Electrophysiological; Renin-Angiotensin System; Shal Potassium Channels; Tetrazoles; Transcription, Genetic; Weight Loss

To investigate the effect of benazepril on atrial cytoskeleton remodeling in atrial fibrillation (AF) canines induced by chronic rapid atrial pacing (RAP).. Twenty canines were randomly divided into 3 groups: (1) Sham-operated group without RAP; (2) AF group: AF established by RAP at 600 beats per minute for 6 weeks; (3) Benazepril group: benazepril was dosed from 1 week pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was measured, collagen volume fraction (CVF) analyzed by Masson staining and the expression and distribution of desmin were assayed by immunohistochemistry. RT-PCR method was used to semi-quantify the mRNA expression of beta-tubulin and desmin.. The diameter of atrial cardiomyocyte increased in AF group [LA:(27.9 +/- 3.8) microm; RA: (26.8 +/- 3.2) microm] and benazepril group[LA: (25.1 +/- 3.4) microm; RA: (25.2 +/- 3.5) microm] than sham-operated group [LA: (19.6 +/- 2.9) microm; RA: (18.7 +/- 2.6) microm] (P < 0.01). CVF increased in AF group than sham-operated group [LA: (16.9 +/- 1.1)% vs (9.2 +/- 0.9)%, RA: (15.7 +/- 2.3)% vs (9.3 +/- 0.8)%, P < 0.01] and it decreased in benazepril group than AF group [LA: (11.3 +/- 0.8)% vs (16.9 +/- 1.1)%, RA: (10.9 +/- 0.8)% vs (15.7 +/- 2.3)%, P < 0.01]. Normal desmin cross-striations were lost in atrial cardiomyocyte and the desmin organization became irregular in AF group. The A values analyzed by immunohistochemistry of desmin increased in AF group than sham-operated group and they decreased in benazepril group than AF group (P < 0.01). The expression of mRNA level of desmin and beta-tubulin were up-regulated in AF group than sham-operated group, (LA:1.0 +/- 0.3 vs 0.6 +/- 0.3, 0.9 +/- 0.4 vs 0.6 +/- 0.3; RA: 1.0 +/- 0.6 vs 0.6 +/- 0.2, 1.1 +/- 0.3 vs 0.7 +/- 0.4, P < 0.01) and they were down-regulated in benazepril group than AF group (LA:0.8 +/- 0.4 vs 1.0 +/- 0.3, 0.7 +/- 0.3 vs 0.9 +/- 0.4; RA:0.7 +/- 0.3 vs 1.0 +/- 0.6, 0.7 +/- 0.3 vs 1.1 +/- 0.3, P < 0.01).. Benazepril can favorably improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Fibrillation; Benzazepines; Cytoskeleton; Desmin; Disease Models, Animal; Dogs; Heart Atria; Myocytes, Cardiac; RNA, Messenger; Tubulin