Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study

Villacorta, Aline Sterque; Villacorta, Humberto; Caldas, José Antônio; Precht, Bernardo Campanário; Porto, Pilar Barreto de Araújo; Rodrigues, Letícia Ubaldo; Neves, Marcos Cesar Danhoni; Xavier, Analúcia Rampazzo; Kanaan, Salim; Mesquita, Cláudio Tinoco; Nóbrega, Antônio Cláudio Lucas da

doi:10.1177/1074248418799364

Cited by 11 publications

(14 citation statements)

References 25 publications

(31 reference statements)

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“…In some patients, vital signs showed a circulatory shock state, requiring vasopressors. Distigmine can induce bradycardia, which is consistent with the report that pyridostigmine, a combination of two molecules in distigmine, shows heart rate reduction in patients with heart failure [26]. In contrast, as in case 2, patients with rivastigmine intoxication developed elevated BP and a relatively increased PR.…”

Section: Discussionsupporting

confidence: 90%

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Sedogawa

Matsuo

2020

JA Clin Rep

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Background: Cholinergic crisis caused by cholinesterase inhibitors is rare but life-threatening. Clinical manifestations are thought to be similar to those caused by organophosphates. Case presentation: A 77-year-old woman on a standard dose of distigmine presented with impaired consciousness, blood pressure (BP) of 69/40 mmHg, a pulse rate (PR) of 60 beats/min, miosis, bronchorrhea, and serum cholinesterase (ChE) of 8 IU/L. After discontinuation of distigmine, altered mental status and pupil miosis were gradually resolved in 5 days with a concomitant increase of serum ChE. A 91-year-old woman presented with a headache, BP of 202/86 mmHg, PR of 83 beats/min, miosis, 9 rivastigmine patches on her knees, and ChE of 22 IU/L. The day after close observation without rivastigmine use, her symptoms were almost resolved with a concomitant increase of serum ChE. Conclusion: Our cases and a literature review suggested that, in contrast to distigmine, rivastigmine-induced cholinergic crisis caused hypertension and tachycardia.

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Section: Discussionsupporting

confidence: 90%

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Sedogawa

Matsuo

2020

JA Clin Rep

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“…Characteristics of the included studies on HFpEF are summarized in Table 1 [15][16][17], and those on HFrEF in Table 2 [18][19][20][21][22][23][24][25][26][27]. A total of 821 patients were enrolled in the 13 included RCTs with duration of follow-up ranging from 7 days to 6 months.…”

Section: Resultsmentioning

confidence: 99%

Effect of Ivabradine on Left Ventricular Diastolic Function, Exercise Tolerance and Quality of Life in Patients With Heart Failure: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2020

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Background: Ivabradine is a heart rate-lowering drug that selectively inhibits the funny (I f ) current of the sinoatrial node. It is currently recommended in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in sinus rhythm and a heart rate of ≥ 70 beats per minute (bpm) at rest. To investigate whether ivabradine has an effect on diastolic dysfunction, exercise tolerance and quality of life (QOL), we conducted a systemic review and meta-analysis of randomized controlled trials (RCTs). Methods: We searched PubMed, EMBASE and Cochrane CentralRegister of Clinical Trials for studies on the effect of ivabradine on left ventricular (LV) diastolic dysfunction, exercise tolerance, QOL, readmission for worsening HF and mortality in both patients with HF with preserved ejection fraction (HFpEF) and HFrEF.Results: Thirteen RCTs with 881 patients met the inclusion criteria. According to the pooled analysis, for the HFpEF subgroup, treatment with ivabradine resulted in a decrease in early diastolic mitral inflow to late diastolic flow ratio (E/A) (standardized mean difference (SMD): -0.53; 95% confidence interval (CI): -0.99, -0.07; P < 0.000) and increase in peak oxygen uptake during exercise (VO 2 ) (SMD: 0.05; 95% CI: -0.35, 0.45; P < 0.00; I 2 = 95.1%). Similar effect was seen in the HFrEF subgroup with decrease in E/A ratio (SMD: -0.33; 95% CI: -0.59, -0.06; P < 0.000) and early diastolic mitral inflow to annular velocity ratio (E/e') (SMD: -1.01; 95% CI: -1.49, -0.54; P < 0.012). Ivabradine therapy increased peak VO 2 and 6-min walk test (6MWT) in HFrEF patients (SMD: 0.83; 95% CI: 0.35, 1.32; P < 0.00; I 2 = 97.5% and SMD: 1.11; 95% CI: 0.82, 1.41; P < 0.000, respectively). There was also significant reduction in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (SMD: -0.68; 95% CI: -0.91, -0.45; P < 0.000). However, there was no significant difference in readmission for worsening HF and all-cause mortality between ivabradine and control (risk ratio (RR): 1.44; 95% CI: 0.73, 2.16; P < 0.148 and RR: 0.76; 95% CI: 0.19, 1.33; P < 0.907, respectively). Conclusions:Ivabradine therapy is associated with improved LV diastolic function, increases exercise tolerance and hence QOL, but it has no significant effect on readmission for worsening HF and allcause mortality.

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“…It was effective at reducing the incidence of ventricular arrhythmia and improving heart rate variability in patients with heart failure [ 18 ]. Further, it was equally effective at reducing heart rate when compared to ivabradine, which was proven effective at reducing hospitalization and mortality due to chronic heart failure [ 19 ]. In a study related to the (atherosclerosis–methylprednisolone [a steroid]) pair, the group exposed to the inhaled steroid had a lower incidence of atherosclerosis compared with the non-exposed group, suggesting its effectiveness in preventing atherosclerosis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Article In Pressmentioning

confidence: 99%

Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus

et al. 2022

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Background: Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates' effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications. Methods: Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records. Results: We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44). Conclusion:To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.

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Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study

Abstract: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.

Cited by 11 publications

References 25 publications

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Opposite changes in blood pressure and pulse rate in two patients with distigmine and rivastigmine intoxication

Effect of Ivabradine on Left Ventricular Diastolic Function, Exercise Tolerance and Quality of Life in Patients With Heart Failure: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Drug Repositioning Using Temporal Trajectories of Accompanying Comorbidities in Diabetes Mellitus

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