Statistical Difference In All-cause Mortality Research Articles

Efficacy and safety of total parathyroidectomy with autotransplantation vs. subtotal parathyroidectomy for secondary hyperparathyroidism: A retrospective study

BackgroundNo consensus has been reached on the best surgical approach for secondary hyperparathyroidism (SHPT). We evaluated the short-term and long-term efficacy and safety of total parathyroidectomy with autotransplantation (TPTX + AT) and subtotal parathyroidectomy (SPTX). MethodsWe retrospectively analyzed the data of 140 patients undergoing TPTX + AT and 64 undergoing SPTX between 2010 and 2021 in Second Affiliated Hospital of Soochow University, and carried out follow-up. We compared the differences in symptoms, serological examinations, complications and mortality between the two methods, and explored the independent risk factors of secondary hyperparathyroidism recurrence. ResultsIn short time after surgery, serum intact parathyroid hormone and calcium level was lower in TPTX + AT group than that in SPTX group (both P < 0.05). Severe hypocalcemia was more common in TPTX group (P = 0.003). The recurrent rate was 17.1% for TPTX + AT and 34.4% for SPTX (P = 0.006). There was no statistical difference in all-cause mortality, cardiovascular events, cardiovascular mortality between the two methods. Higher preoperative serum phosphorus level (HR: 1.929 95% CI 1.045–3.563, P = 0.011) and the SPTX surgical method (HR: 2.309, 95% CI 1.276–4.176, P = 0.006) were found to be independent risk factors for SHPT recurrence. ConclusionsCompared with SPTX, TPTX + AT is more effective in reducing the recurrent risk of SHPT without increasing the risk of all-cause mortality and cardiovascular events.

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Parkash et al (Circulation 2022;145:1693, PMID 35313733) conducted a multicenter, open-label trial randomizing patients with paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II-III heart failure (HF), and elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events. Secondary outcomes included left ventricular ejection fraction (LVEF), 6-minute walk test, and NT-proBNP. Overall, 411 patients were randomized to ablation (n = 214) or rate control (n = 197). The primary outcome occurred in 50 patients (23.4%) in the ablation group and 64 patients (32.5%) in the rate control group (hazard ratio 0.71; P = .066). LVEF increased in the ablation group (10.1% ± 1.2% vs 3.8% ± 1.2%; P = .017); 6-minute walk distance improved (44.9 ± 9.1 m vs 27.5 ± 9.7 m; P = .025) and NT-proBNP decreased (−77.1% vs −39.2%; P < .0001). Adverse events were observed in 50% of patients in both groups. The authors conclude that there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control vs rate control. There was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control.

Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II to III HF, and elevated NT-proBNP (N-terminal pro brain natriuretic peptide) were randomly assigned to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow-up of 2 years. Secondary outcomes included left ventricular ejection fraction, 6-minute walk test, and NT-proBNP. Quality of life was measured using the Minnesota Living With Heart Failure Questionnaire and the AF Effect on Quality of Life. The primary analysis was time-to-event using Cox proportional hazards modeling. The trial was stopped early because of a determination of apparent futility by the Data Safety Monitoring Committee. From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49-1.03]; P=0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P=0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P=0.025), and NT-proBNP demonstrated a decrease (mean change -77.1% versus -39.2%, P<0.0001). Minnesota Living With Heart Failure Questionnaire demonstrated greater improvement in the ablation-based rhythm-control group (least-squares mean difference of -5.4 [95% CI, -10.5 to -0.3]; P=0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7-10.7]; P=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. URL: https://www. gov; Unique identifier: NCT01420393.

Antibiotic Treatment of Pulmonary Infections: An Umbrella Review and Evidence Map.

Background: Considering the global burden of pulmonary infections, there is an urgent need for optimal empirical antimicrobial therapy strategies for pulmonary infections, which should rely on reliable evidence. Therefore, we aim to investigate the optimal treatment options for pulmonary infections in adults and assess the strength of that evidence. Methods: We searched PubMed, Embase, the Cochrane Library, and China Biology Medicine disc to identify systematic reviews and meta-analyses of randomized controlled trials (RCTs) focusing on antimicrobial treatments for pulmonary infections. The outcomes of the included meta-analyses should include all-cause mortality or clinical treatment success. For each meta-analysis, we estimated relative risk (RR) with 95% CI. We also created an evidence map to show the efficacy of each antimicrobial treatment strategy and the certainty of the evidence. Results: Twenty-six meta-analyses and two new RCTs were included that contained 31 types of antimicrobial therapy strategies. We found that carbapenems were related to lower mortality than other β-lactams or fluoroquinolones alone or in combination with aminoglycosides for HAP patients (RR 0.76, 95% CI: 0.58–0.99). There was no statistical difference in all-cause mortality between the other antimicrobial therapy strategies. As for clinical cure, treatment with fluoroquinolones was associated with better success versus macrolides or β-lactams alone for CAP patients in both the intention-to-treat (ITT) population (RR 1.22, 95% CI: 1.02–1.47) and clinically evaluable (CE) population (RR 1.37, 95% CI: 1.11–1.68). Treatment with carbapenems showed a better clinical cure over non-carbapenems for VAP patients (RR 1.21, 95% CI: 1.05–1.4). Adjunctive inhaled antibiotics compared with intravenous antibiotics alone showed a benefit for VAP (RR 1.2, 95% CI: 1.05–1.35). In addition, adjunctive nebulized aminoglycoside for nosocomial pneumonia was associated with a higher cure rate versus intravenous antibiotics alone in the ITT population (RR 1.28, 95% CI: 1.04–1.57), while no statistical difference in clinical cure was observed between other intervention groups. Conclusions: We cannot evaluate which antibiotic is the best choice for the treatment of pulmonary infection. Carbapenems or adjunctive inhaled antibiotics showed a reasonable choice for HAP or VAP. However, we do not find a statistical difference between most antimicrobial therapy strategies for CAP patients.

The prognostic impact of catheter ablation for atrial fibrillation after heart failure hospitalization on long-term mortality – Propensity-score matching analysis

Abstract Background In the last two decades, catheter ablation (CA) for atrial fibrillation (AF) including pulmonary vein isolation (PVI) has been developed as a standard and effective treatment for atrial fibrillation (AF). In patients with chronic heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF), PVI CA for AF dramatically improves LVEF, resulting in better clinical prognoses. On the contrary, there still has been no data that PVI CA for AF improves the prognosis in heart failure patients with preserved LVEF (HFpEF). Purpose The aim of this study was to evaluate the prognostic impact of PVI CA for AF after the hospitalization due to decompensation of heart failureHF, focusing on LVEF. Methods From the database including 1,793 consecutive patients who were hospitalized due to congestive HF, we ultimately analyzed 624 AF patients who were discharged alive. They were assigned into two groups due that PVI CA for AF procedure done after the index hospitalization for HF; the PVI CA group (n=62) and Non-PVI CA group (n=562). For the two groups, we performed propensity-score (PS) matching using variables as follows: age, sex, LVEF, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) at discharge. Further analysis was performed separately in HFrEF (LVEF &amp;lt;50%) and HFpEF (LVEF &amp;gt;50%). The primary endpoint of this study was death from any cause. Results In unmatched patients, Kaplan-Meier analysis showed that patients in the PVI CA group had a significantly lower all-cause mortality than those in the Non-PVI CA group during 678 median follow-up period (Log-rank test: P=0.003, Figure A). In 96 PS-matched patients, patients in the PVI CA group still had lower mortality rate than those in the Non-PVI CA group (hazard ratio 0.28, 95% confidence interval 0.09–0.86, p=0.018, Figure B). When the whole study population was classified into HFrEF and HFpEF, HFrEF patients who received PVI showed a significantly lower mortality than those who did not (p=0.007); whereas, in HFpEF patients, PVI CA for AF did not make statistical difference in all-cause mortality (p=0.061). Conclusions In this observational study, PVI CA for AF may improve the mortality in HF patients with reduced LVEF. However, the prognostic impact of PVI CA for AF was not observed in HF patients with preserved LVEF. Funding Acknowledgement Type of funding source: None

Coexistence of clinically significant obstructive sleep apnea with physician-diagnosed asthma or chronic obstructive pulmonary disease: A population study of prevalence and mortality

RATIONALE: Despite potential importance, the epidemiology of coexisting obstructive sleep apnea and asthma (OSA/asthma) or OSA and COPD (OSA/COPD) has not been well studied. OBJECTIVES To access the trends in prevalence and mortality of coexisting OSA/asthma or OSA/COPD among individuals 35-years or older in Ontario, Canada. METHODS AND MEASUREMENTS: We conducted a population-based study using provincial health administrative data. Validated case definitions were used to identify individuals with physician-diagnosed asthma or COPD. Individuals with clinically significant OSA were those who initiated positive airway pressure treatment. Age- and sex-standardized annual prevalence and mortality rates were estimated and compared from 2009 to 2015. Generalized linear models were used. MAIN RESULTS: The standardized prevalence increased from 0.42% to 0.66% for OSA/asthma and from 0.23% to 0.35% for OSA/COPD from 2009 to 2015. The standardized all-cause mortality rates remained stable over time. Both coexistence conditions were associated with higher mortality than OSA alone. Adjusting for age, sex and calendar year, mortality was modestly but statistically significantly higher for OSA/asthma than asthma alone (OR = 1.03; 1.00–1.06) with the highest OR noted in 35-49 years old group (1.85; 1.63–2.09). There was no statistical difference in all-cause mortality among individuals with coexisting OSA/COPD compared to patients with COPD alone. In women only, OSA/COPD was associated with a modestly higher mortality than COPD alone (OR = 1.05; 1.01–1.09). CONCLUSIONS In this population-based study of coexisting clinically significant OSA and chronic lung disease, we report population prevalence and mortality, including their age and sex distribution. These findings can alert health care providers and policymakers to the large and increasing burden of these coexisting conditions and high-risk groups.

Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens.

Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI + mTA or CNI + AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections, and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fifteen eligible studies (5 studies comparing mTA + AM vs. CNI + AM, 9 comparing CNI + mTA vs. CNI + AM, 1 comparing mTA + AM vs. CNI + mTA, 8 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI + mTA (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI + AM (OR 0.26, 95% CI 0.12-0.56) and with CNI + mTA (OR 0.16, 95% CI 0.07-0.33) compared with mTA + AM without significant heterogeneity (I2= 43%, p = 0.9). CMV infections were significantly lower with mTA + AM (OR 0.13, 95% CI 0.03-0.46) and with CNI + mTA (OR 0.27, 95% CI 0.2-0.38) compared with CNI + AM without heterogeneity. mTA + AM led to higher eGFR compared with CNI + AM (9.06ml/min/1.73m2, 95% CI 3.15-14.97) and CNI + Mta (9.64ml/min/1.73m2, 95% CI 0.91-18.36), but the heterogeneity among studies was significant. CNI + mTA ranked better for CAV (p = 0.78), and acute rejection (p = 0.99) while mTA + AM for CMV infection (p = 0.94) and improvement in renal function (p = 0.93) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI + mTA was associated with lower CAV rates, and acute rejection, while mTA + AM with less CMV infection post HT.

Comparative Outcomes of Maintenance Immunosuppression Regimens in Heart Transplantation: Insights from Network Meta-Analysis

Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI+mTA or CNI+ AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fourteen eligible studies (5 studies comparing mTA+AM vs. CNI+AM, 9 comparing CNI+mTA vs. CNI+ AM, 7 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI+ mTA (Odds Ratio [OR] 0.53, 95% Confidence Interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI+AM (OR 0.25, 95% CI 0.07-0.96) and with CNI+ mTA (OR 0.17, 95% CI 0.04-0.71) (Figure) compared with mTA+AM with significant heterogeneity (I2=69.5%, p=0.003). CMV infections were significantly lower with mTA+AM (OR 0.13, 95% CI 0.03-0.46) and with CNI+ mTA (OR 0.27, 95% CI 0.2-0.38) (Figure) compared with CNI+AM without heterogeneity. mTA+AM lead to significant improvement of eGFR compared with CNI+ mTA. CNI+ mTA ranked better for CAV (p=0.78), CNI+AM for acute rejection (p=0.96) and mTA+AM for CMV infection (p=0.94) and improvement in renal function (p=0.86) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI+ mTA was associated with lower CAV rates, CNI+AM with less rejection, and mTA+AM with less CMV infection and improved eGFR post HT.

ST-Segment– Elevation Myocardial Infarction for Pharmacoinvasive Strategy or Primary Percutaneous Coronary Intervention in Gaza (STEPP- PCI)

Background A primary percutaneous coronary intervention (PCI) Primary PCI continues to be the optimal reperfusion therapy in patients with ST elevation myocardial infarction however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed. This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with primary (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in Gaza. Methods: We randomized 145 patients presenting within 2 hours of symptom onset of acute ST elevation myocardial infarction to primary CPI (PCI) or for pharmaco-invasive PCI 2-24 hours after streptokinase, except in the event of failed reperfusion, in which case, emergency angiography was recommended. The primary endpoint a composite of death, shock and congestive heart failure at 30 days. Results: Total 145 patients with mean age 56.5+10.48 years. (The mean age of patients is) The primary endpoint in primary PCI (17%) and in pharmaco-invasive PCI (16.1%) p = 0.24.???? There was no difference in 30-day mortality (4.7 % in primary PCI and 4.9% in pharmacoinvasive strategy (P=0.94). Secondary endpoints:Emergency angiography was required in 39.5% of the patients in the pharmaco-invasive strategy and the median time for underwent angiography was 6 hours after randomization. TIMI major bleeding occurred among 4 patients ( 4.9 % ) in the pharmacoinvasive group and in 2 patients (3.1%) of the primary PCI group (P = 0.59).The pharmacoinvasive group had 1.9 times the odds of having TIMI major bleed compared with the primary PCI group Conclusions In this randomized trial, early-presenting STEMI patients unable to undergo primary PCI within 1 hour (median, 75±20 minutes) were randomized to primary PCI or a pharmaco-invasive strategy with streptokinase followed by PCI. At 1 month follow-up, there was no statistical difference in all-cause mortality, heart failure or shock. This study suggests that, if primary PCI cannot be performed within 1 hour of presentation, a pharmaco-invasive strategy may be as good as primary PCI.

Impact of body mass index on survival in patients undergoing peritoneal dialysis: Analysis of data from the Insan Memorial End-Stage Renal Disease Registry of Korea (1985-2014).

BackgroundSignificant increases in the prevalence of obesity have been observed among patients with peritoneal dialysis (PD). The impact of body mass index (BMI) on survival remains unknown in Korean PD patients.MethodsAmong data of 80,674 patients on PD acquired from the Insan Memorial ESRD Registry database for the years 1985 to 2014, 6,071 cases were analyzed. Subjects were classified by baseline BMI; < 21.19 kg/m2 (quartile 1, n = 1,518), 21.19 to 23.18 kg/m2 (quartile 2, reference; n = 1,453), 23.19 to 25.71 kg/m2 (quartile 3, n = 1,583), and > 25.71 kg/m2 (quartile 4, n = 1,517).ResultsMean age was 65.8 years, and baseline BMI was 23.57 kg/m2. Numbers of male and diabetic patients were 3,492 (57.5%) and 2,192 (36.1%), respectively. Among 6,071 cases, 2,229 (36.7%) all-cause deaths occurred. As a whole, Kaplan–Meier survival curves according to BMI quartiles was significantly different (P = 0.001). All-cause mortality was significantly higher in quartile 4 than in the reference (hazard ratio [HR] = 1.154, 95% confidence interval [CI], 1.025–1.300; P = 0.018). There was no statistical difference in all-cause mortality among BMI quartiles in diabetic patients on PD. In non-diabetic patients, all-cause mortality of quartiles 1 and 3 was not different from the reference, but the HR was 1.176 times higher in quartile 4 (95% CI, 1.024–1.350; P = 0.022).ConclusionBaseline BMI > 25.71 kg/m2 seems to be an important risk factor for all-cause mortality in Korean PD patients.

Antibiotics for ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients.While guidelines exist for the antibiotic treatment of hospital-acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP. The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator-associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016. Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new-onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review. Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non-carbapenem therapy. We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies.We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence.For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study.We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

Azimilide, A Novel Oral Class III Antiarrhythmic for Both Supraventricular and Ventricular Arrhythmias

Azimilide is an investigational Class III antiarrhythmic that has been developed for treating both supraventricular and ventricular tachyarrhythmias. Similar to other Class III antiarrhythmics, azimilide prolongs myocardial repolarization in a dose-dependent manner by increasing the action potential duration, QT interval, and effective refractory period. The most frequent reported side effect is headache, with rare serious adverse events of early reversible neutropenia and Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been low. Azimilide has very predictable pharmacokinetics, is predominantly hepatically metabolized, and has no significant drug interactions with digoxin or warfarin. In animal models, azimilide has been shown to be very effective in suppressing both atrial and ventricular tachyarrhythmias, decreasing the defibrillation energy requirement, and preventing post-myocardial infarction ventricular tachycardia and fibrillation. Clinically, in a series of 4 double-blind, randomized, placebo-controlled trials, the Azimilide Supraventricular Arrhythmia Program which included over 1000 patients and approximately 70% with structural heart disease, azimilide showed a significant prolongation in the time to first recurrence of paroxysmal supraventricular tachycardia or atrial fibrillation/flutter. With respect to ventricular tachyarrhythmias, the AzimiLide post-Infarct surVival Evaluation Trial was a large randomized, multinational, prospective, placebo-controlled study in recent survivors of myocardial infarction at high risk for sudden cardiac death. After 1 year of follow-up, this study showed no statistical difference in all-cause mortality between placebo and azimilide. However, azimilide did statistically reduce the incidence of new atrial fibrillation. Further trials are necessary to evaluate the efficacy of azimilide in patients with symptomatic ventricular arrhythmias.