Anand Deshmukh

Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling.  We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an ‘outlier’ manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

Quetiapine and the need for a thorough QT/QTc study

The Food and Drug Administration (FDA) directed AstraZeneca in 2011 to add a warning to the labeling of the atypical antipsychotic agent quetiapine (Seroquel) about quetiapine-induced QTc interval prolongation and the potential for drug-induced torsade de pointes (TdP). This warning was updated the following year. Rather than relying on a thorough QT/QTc (TQT) study, this update was based on postmarketing reports of patients (1) overdosing on quetiapine, (2) having severe hypokalemia, or (3) receiving drugs associated with QTc interval prolongation such as (1) class I-A or class III antiarrhythmics, (2) certain antipsychotics (eg, ziprasidone, chlorpromazine, thioridazine), (3) certain antibiotics (eg, gatifloxacin, moxifloxacin), or (4) any other classes of drugs linked to QTc interval prolongation (eg, pentamidine, L-methadyl acetate, methadone). Interestingly, of the 3095 patients, 2 (0.06%) developed QTc interval prolongation of more than 500 milliseconds in quetiapine premarketing trials. They were older women with dementia. There was no link between quetiapine dose and QTc interval prolongation. Here, we evaluate available information on quetiapine in respect of QTc inteval prolongation and TdP, taking into account both information from preclinical experimental studies and human data. A striking feature of the latter is a lack of information from ‘‘thorough QT’’ (TQT) studies. We argue that TQT data for quetiapine would be invaluable in reaching an integrated assessment of its cardiac risk.

Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and new directions derived from a systematic review of case reports.

Objective: In the light of the recent United States Food and Drug Administration (FDA) warning to clinicians on using previously approved doses of citalopram because of the purported higher risk of torsade de pointes (TdP), we pursued the broader question: are selective serotonin reuptake inhibitor (SSRI) antidepressant agents as a group unsafe because they might induce QTc interval prolongation and TdP? Method: We reviewed the literature and found only 15 case reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated QTc interval prolongation linking to TdP. Results: A total of 13 cases contained sufficient information for analysis. In the setting of TdP, QTc interval prolongation does not clearly relate to SSRI dose. Conclusion: Applying conventional statistics as the FDA does may not be the best tool to study this phenomenon because SSRI-associated TdP is a very rare event and hence best understood as an ‘extreme outlier’. Despite the limitations inherent in case report material, case reports on drug-associated QTc interval prolongation and TdP provide valuable information that should be considered along with other sources of information for clinical guidance.

Efficacy and safety of transulnar coronary angiography and interventions--a single center experience.

To evaluate the efficacy and long‐term safety of transulnar approach in complex coronary interventions.

SSRIs and torsade de pointes New concepts and new directions derived from a systematic review of case reports

Objective: In the light of the recent United States Food and Drug Administration (FDA) warning to clinicians on using previously approved doses of citalopram because of the purported higher risk of torsade de pointes (TdP), we pursued the broader question: are selective serotonin reuptake inhibitor (SSRI) antidepressant agents as a group unsafe because they might induce QTc interval prolongation and TdP? Method: We reviewed the literature and found only 15 case reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated QTc interval prolongation linking to TdP. Results: A total of 13 cases contained sufficient information for analysis. In the setting of TdP, QTc interval prolongation does not clearly relate to SSRI dose. Conclusion: Applying conventional statistics as the FDA does may not be the best tool to study this phenomenon because SSRI-associated TdP is a very rare event and hence best understood as an ‘extreme outlier’. Despite the limitations inherent in case report material, case reports on drug-associated QTc interval prolongation and TdP provide valuable information that should be considered along with other sources of information for clinical guidance.

Antithrombotic regimens in patients with indication for long-term anticoagulation undergoing coronary interventions-systematic analysis, review of literature, and implications on management.

There is lack of consensus regarding use of antithrombotic therapy (AT) in patients with indications for long-term anticoagulation who undergo percutaneous coronary intervention. We sought to evaluate the safety and efficacy of various antithrombotic regimens in this patient population. We conducted a Medline search for all English language, full-text articles from January 2000 to June 2009 that evaluated major cardiovascular outcomes in patients with indications for anticoagulation who undergo percutaneous coronary intervention. Data were analyzed from these studies to calculate annual incidence of major bleeding, stroke, and stent thrombosis with various antithrombotic regimens. Major bleeding events were calculated at 30 days and at 1 year. Ten retrospective studies, 1 post hoc analysis of a major registry, and 2 prospective studies qualified for our analysis. Atrial fibrillation was the most common indication for anticoagulation. Risk of major bleeding was 1.5% at 30 days and 5.2% at 1 year with triple AT (aspirin + warfarin + clopidogrel/ticlopidine). Dual antiplatelet therapy (aspirin + clopidogrel/ticlopidine) was associated with 2.4% annual risk of major bleeding. The annual incidence of both ischemic stroke and stent thrombosis was 1% with triple antithrombotic regimen. Risk of major bleeding increases proportionately with incremental duration of triple AT. Triple AT is effective in the prevention of ischemic stroke and stent thrombosis. Dual antiplatelet regimen is effective in patients with low annual risk of ischemic stroke (<4%; CHADS-2 score <2) due to lower annual risk of bleeding associated with this regimen (2.4%).

Spontaneous hemopericardium leading to cardiac tamponade in a patient with essential thrombocythemia.

Acute cardiac tamponade requires urgent diagnosis and treatment. Spontaneous hemopericardium leading to cardiac tamponade as an initial manifestation of essential thrombocythemia (ET) has never been reported in the literature. We report a case of a 72-year-old Caucasian female who presented with spontaneous hemopericardium and tamponade requiring emergent pericardiocentesis. The patient was subsequently diagnosed to have ET. ET is characterized by elevated platelet counts that can lead to thrombosis but paradoxically it can also lead to a bleeding diathesis. Physicians should be aware of this complication so that timely life-saving measures can be taken if this complication arises.

Selective serotonin reuptake inhibitors and torsade de pointes

Objective: In the light of the recent United States Food and Drug Administration (FDA) warning to clinicians on using previously approved doses of citalopram because of the purported higher risk of torsade de pointes (TdP), we pursued the broader question: are selective serotonin reuptake inhibitor (SSRI) antidepressant agents as a group unsafe because they might induce QTc interval prolongation and TdP? Method: We reviewed the literature and found only 15 case reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated QTc interval prolongation linking to TdP. Results: A total of 13 cases contained sufficient information for analysis. In the setting of TdP, QTc interval prolongation does not clearly relate to SSRI dose. Conclusion: Applying conventional statistics as the FDA does may not be the best tool to study this phenomenon because SSRI-associated TdP is a very rare event and hence best understood as an ‘extreme outlier’. Despite the limitations inherent in case report material, case reports on drug-associated QTc interval prolongation and TdP provide valuable information that should be considered along with other sources of information for clinical guidance.

SAFETY AND FEASIBILITY OF SAME–DAY PCI AND CAROTID ARTERY STENTING

methods: We analyzed patients undergoing CAS at a tertiary care center between June 2003 & July 2012 who were planned to undergo same day PCI. Patients undergoing the procedure after March 2007 were prospectively followed for 1 year & in remaining patients, data was retrospectively retrieved by chart review to evaluate safety & efficacy endpoints. All patients underwent PCI prior to undergoing CAS. All CAS was performed using filter-wire based distal protection technique. Successful PCI & CAS were defined as residual stenosis less than 30%.

COMPARISON OF OUTCOMES OF PATIENTS PRESENTING WITH INFERIOR STEMI WITH PROXIMAL AND DISTAL RIGHT CORONARY ARTERY OBSTRUCTION

While, proximal right coronary artery (RCA) occlusion in patients with inferior STEMI would suggest right ventricular (RV) involvement, the effect of location of RCA occlusion on outcomes has not been studied. We sought to evaluate the impact of site of occlusion of RCA on outcomes of patients with