QT interval prolongation and torsades de pointes in a patient undergoing treatment with vorinostat: A case report and review of the literature

Vorinostat is a histone deacetylase inhibitor used in the treatment of recurrent or persistent cases of cutaneous T-cell lymphoma (CTCL). A retrospective review of 116 patients from phase I and II clinical trials who had a baseline and at least one subsequent ECG revealed that four patients had Grade 2 and one patient had Grade 3 QTc interval prolongation; however, a MEDLINE search found no reported cases of torsades de pointes (TdP) in patients treated with vorinostat. We describe the case of a 49 year-old male with a history of CTCL actively undergoing treatment with vorinostat. During day 1 of hospitalization, he developed a pulseless polymorphic ventricular tachycardia requiring resuscitation. He was found to have a QTc of 826 ms. Following correction of potassium and magnesium, QTc gradually decreased and no further ventricular arrhythmia was noted. Other factors implicated in this case included concurrent sertraline and doxepin therapy (both drugs have been associated with the development of TdP in overdose). The mechanism of development of TdP in this patient is postulated to be related to vorinostat use in combination with hypokalemia and concomitant treatment with medications associated with QTc prolongation. This case highlights the importance of post-market surveillance

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention:The ROCKET AF Trial

AbstractObjectivesThe authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).BackgroundThe frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown.MethodsThe study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial.ResultsAmong 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups.ConclusionsIn patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy

Perioperative beta blockade in noncardiac surgery: A systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American college of cardiology/American heart association task force on practice guidelines

Objective: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates.Methods: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions.Results: We identified 17 studies, of which 16 were RCTs (12,043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI:1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR:0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded.Conclusions: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap

Perioperative beta blockade in noncardiac surgery: A systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American college of cardiology/American heart association task force on practice guidelines

Objective: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates.Methods: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions.Results: We identified 17 studies, of which 16 were RCTs (12 043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI: 1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR: 0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded.Conclusions: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap

Perioperative beta blockade in noncardiac surgery: A systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American college of cardiology/American heart association task force on practice guidelines

Objective: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates.Methods: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions.Results: We identified 17 studies, of which 16 were RCTs (12,043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI:1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR:0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded.Conclusions: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap