Drug-drug interactions contributing to QT prolongation in cardiac intensive care units

Purpose

To determine the most common drug-drug interaction (DDI) pairs contributing to QTc prolongation in cardiac intensive care units (ICUs).

Materials and Methods

This retrospective evaluation included patients who were admitted to the cardiac ICUs between January 2009 and July 2009 aged ≥ 18 years with electrocardiographic evidence of a QTc ≥ 500 ms. Patients receiving at least two concomitant drugs known to prolong the QT interval were considered to experience a pharmacodynamic DDI. Drugs causing CYP450 inhibition of the metabolism of QT prolonging medications were considered to cause pharmacokinetic DDIs. The causality between drug and QTc prolongation was evaluated with an objective scale.

Results

One hundred eighty-seven patients experienced QT prolongation out of a total of 501 patients (37%) admitted during the study period. Forty-three percent and 47% of patients experienced 133 and 179 temporally-related pharmacodynamic and pharmacokinetic interactions, respectively. The most common medications related to these DDIs were ondansetron, amiodarone, metronidazole, and haloperidol.

Conclusion

DDIs may be a significant cause of QT prolongation in cardiac ICUs. These data can be used to educate clinicians on safe medication use. Computerized clinical decision support could be applied to aid in the detection of these events.     

Inappropriate prescribing in older residents of Australian care homes

What is known and objective: The incidence of inappropriate prescribing is higher amongst the older age group than the younger population. Inappropriate prescribing potentially leads to drug‐related problems such as adverse drug reactions. We aimed to determine the prevalence of inappropriate prescribing in residents of Tasmanian (Australia) residential care homes using Beers and McLeod criteria. Methods: Patient demographics, medical conditions and medications were collected from medical records. The patients who fulfilled either Beers or McLeod criteria were identified and the characteristics of these patients were then compared. Results: Data for 2345 residents were collected between 2006 and 2007. There were 1027 (43·8%) patients prescribed at least one inappropriate medication. Beers criteria identified more patients (828 patients, 35·3%) as being prescribed inappropriate medication compared with McLeod criteria (438 patients, 18·7%). Patients taking psychotropic medication/s, more than six medications or diagnosed with five or more medical conditions were more likely to be prescribed an inappropriate medication (P < 0·001). The most frequently identified inappropriate medications included benzodiazepines, amitriptyline, oxybutynin and non‐steroidal anti‐inflammatory drugs. What is new and conclusion: Inappropriate prescribing, as defined by either Beers criteria or McLeod criteria, is relatively common in Australian nursing homes. The prevalence of inappropriate prescribing, and factors influencing it, are consistent with other countries. Both Beers and McLeod criteria are a general guide to prescribing, and do not substitute for professional judgment.     

Adverse drug reactions and drug interactions as causes of hospital admission in oncology

Context

Although several studies have evaluated the frequency of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in general medicine, few studies have looked at the epidemiology of adverse drug events (ADEs) in oncology.

Objectives

We sought to investigate how many hospital admissions in oncology are related to a DDI or an ADR.

Methods

All cancer patients admitted to an oncology ward during an eight-month period had their charts retrospectively evaluated for reasons of hospitalization, using a 4-point scale (definitely, probably, possibly, or unlikely associated) to classify admissions by their probability of being associated with either a DDI or an ADR.

Results

From September 2007 to May 2008, there were 550 hospital admissions and 458 were eligible. Among unplanned admissions (n = 298), 39 (13.0%, 95% confidence interval [CI] 9.4%–17.4%) were considered to be associated with an ADE, 33 (11.0%, 95% CI 7.7%–15.2%) with an ADR, and six (2.0%, 95% CI 0.7%–4.3%) with a DDI. The most common DDIs involved warfarin, captopril, and anti-inflammatory agents, and the most frequent ADR was neutropenic fever post-chemotherapy. Most patients were discharged completely recovered, but two patients died.

Conclusion

Approximately one in 10 unplanned hospitalizations of cancer patients is associated with an ADE. Prospective and population-based studies are warranted to evaluate their magnitude in oncology.     

Factors associated with compliance to thiazide diuretics among 8551 Chinese patients

What is known and Objective: Good compliance to anti‐hypertensive medications has been recognized as a crucial factor to achieve optimal blood pressure control, but there were few studies addressing this issue among ethnic Chinese patients. This study aims to evaluate the factors associated with compliance to thiazide diuretics in a Chinese hypertensive population. Methods: From a clinical database, all adult Chinese patients aged ≥18 years who were prescribed a thiazide diuretic from the public health care sector in one large Territory of Hong Kong during January 2004 to June 2007 and attended at least twice for anti‐hypertensive drug refill were included. Medication Possession Ratios were used to measure drug compliance for each patient, with a level ≥80% defined as compliant. We used binary logistic regression analysis to evaluate the factors associated with good compliance. Results and Discussion: From 8551 eligible patients, 84·5% were compliant (defined as MPR ≥ 80%). Fee payers (adjusted odds ratio [aOR] 1·28; 95% CI 1·12–1·46, P < 0·001) and follow‐up visitors (aOR 2·47, 95% CI 2·13–2·87, P < 0·001) were significantly associated with better anti‐hypertensive compliance. Patients who were newly prescribed thiazide diuretics and those with poorer socioeconomic status were more likely to be non‐compliant to anti‐hypertensive therapies. Patients’ age, gender and number of co‐morbidities were not significant associated factors. What is new and Conclusion: Among Chinese patients, those who were newly prescribed thiazide diuretics and those with poorer socioeconomic status were more likely to be non‐compliant to anti‐hypertensive therapies. Closer monitoring and more intensive compliance‐enhancing strategies had to be targeted towards these patients to enhance clinical outcomes.     

Impact of a self-administration of medications programme on elderly inpatients' competence to manage medications: a pilot study

What is known and objectives: Changes to medication regimens and failure to involve patients in management of their medications whilst in hospital may result in medication errors or non‐adherence at home after discharge. Self‐administration of medications programmes (SAMP) have been used to address this issue. The objective of this study was to assess the impact of a SAMP on elderly hospital inpatients’ competence to manage medications and their medication adherence behaviours. Methods: The SAMP comprised three stages: education, progressing to supervised self‐administration and finally to independent self‐administration. Decisions to progress patients to the next level, and whether they passed or failed the SAMP, were made by the ward pharmacist and nursing staff. The Drug Regimen Unassisted Grading Scale (DRUGS) was used to assess patients’ competence to manage medications at various time points. Tablet count and the Tool for Adherence Behaviour Screening (TABS) were used as adherence measures. Results and discussion: Participants (n = 24) with a mean age of 77·4 years, were mainly female and generally had a high level of functioning. They were prescribed a mean of 9·0 medications at the time of commencing the SAMP. Twenty‐two of the 24 participants successfully completed the SAMP. DRUGS scores at discharge improved significantly (P < 0·001) compared with that before commencement of medication self‐administration. Participants reported a significant decrease (P = 0·02) in non‐adherent behaviour and a trend towards improved adherent behaviour (P = 0·08) after participation in the SAMP. What is new and conclusion: An inpatient SAMP improved elderly patients’ ability to competently manage and adhere to their prescribed medications regimen. This finding needs to be confirmed in a larger controlled trial.     

Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients

Study Objective

The aim of the study was to evaluate the impact of prospective review of significant drug-drug interactions (DDIs) occurring in medical intensive care unit (MICU) patients by the critical care pharmacist participating in patient care rounds on improvement of safer and more efficacious medication use.

Study Design

A prospective consecutive 10-week study was conducted in the MICU, St Luke's/Roosevelt Hospital Center (St Luke's site), New York, NY.This study compared baseline period when clinical pharmacist services were not provided with the period when each patient's profile was reviewed daily during MICU rounds and interactions were minimized. The study examined whether the presence of critical care pharmacist would decrease the number of significant DDIs in the MICU. Impact of decreasing presence of severe DDIs on length of stay (LOS) and discharge status was also evaluated.

Results

Having a pharmacist on rounds resulted in statistically significant decrease in number of clinically important interactions requiring therapy modification, rated D-X (Poisson regression B = −1.036; 95% confidence interval, −1.318 to −0.753; P < .01). The coefficient (−1.036) indicates the incidence rate ratio of 0.35, meaning that the presence of clinical pharmacist in MICU rounds decreased DDI rate by 65%.According to the multiple linear regression, lower number of DDIs was associated with shorter LOS (P < .01).Inpatient mortality rate was lower in the intervention group compared with the preintervention group. Number of DDIs was not significantly associated with mortality based on simple regression (P = .45) or multiple regression analysis (P = .09).

Conclusion

Implementing a DDI screening procedure results in significantly lower number of important DDI in the MICU and shortens LOS.     

Comparing the cumulative incidences of add‐on therapy among the major antihypertensive classes in 2531 Asian patients: a cohort study

Background: Published literature addressing the efficacy of different antihypertensive drug classes among Asian patients is scarce. Methods: This cohort study included all patients prescribed their first‐ever antihypertensive monotherapy without concomitant use of chronic medications in two primary care clinics in Hong Kong during 1990–2002. The incidence of add‐on therapy within 48 weeks because of suboptimal blood pressure control was evaluated and compared among different age and gender groups. Results and discussion: Among the 2531 patients, the incidence of add‐on therapy among users of angiotensin converting enzyme inhibitors (ACEI) was highest in young females (31·1%, 95% CI 22·2%, 40·0%, P < 0·001) and elderly females (18·0%, 95% CI 11·3%, 24·7%, P = 0·049) as compared with thiazide diuretics, beta‐blockers and calcium channel blockers. The incidence of add‐on therapy among young males (20·3%, 95% CI 11·1%, 29·5%; P > 0·50) and elderly males (12·5%, 95% CI 3·8%, 21·2%) was also highest with the ACEI than other drug classes although statistical significance was not reached. Conclusion: The incidence of add‐on therapy among first‐time antiypertensives appear to be significantly different between drug classes. This deserves further investigation.     

Emergency department admissions induced by drug–drug interactions in the elderly: A cross‐sectional study

The elderly people are increasingly exposed to polymedication and therefore to the risks of drug–drug interactions (DDIs). However, there are few data available on the clinical consequences of these drug combinations. We investigated the impact of the various DDIs classified as severe in terms of emergency admissions in the elderly. A cross‐sectional study was conducted using information from the emergency department admissions of Bordeaux University Hospital between September 2016 and August 2017. Events of interest were frequency of concomitant uses of interacting drugs that are contraindicated or warned against and frequency of emergency admissions due to contraindicated or warned against concomitant uses of interacting drugs. Five thousand, eight hundred sixty (5860) admissions to the emergency department were analyzed. A total of 375 (6.4%) contraindicated or warned against concomitant uses were identified, including 163 contraindicated (43.5%) and 212 warned against (56.5%). Reason for admission appeared likely related to the underlying DDI in 58 cases. Within these, 36 admissions were assessed as probably due to a DDI (0.6% of hospitalizations) and 22 as certainly (0.4% of hospitalizations). Of these, there were 24 (45%) admissions related to a long QT syndrome (LQTS), nine (16%) related to a drug overdose, and eight (14%) related to a hemorrhage. An antidepressant was involved in 22 of the 24 cases of LQTS. Seven of the eight cases of hemorrhage involved the antithrombotic agents / non‐steroidal anti‐inflammatory drugs combination. Elderly patients admitted to emergency departments are particularly exposed to high‐risk potential DDIs. These drug combinations lead mainly to LQTS and involve certain antidepressants.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

The prevalence of polypharmacy is high in elderly patients admitted to the emergency department, which theoretically exposes this population to many potential drug–drug‐interactions (DDIs).

• WHAT QUESTION DID THIS STUDY ADDRESS?

What is the real clinical impact of potential DDIs classified as severe?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Reason for emergency admission appeared likely related to a potential DDI for 0.4–1% of elderly patients. Among the drugs involved, psychotropic drugs and in particular two antidepressants: citalopram and escitalopram, are the drugs which seem to cause the most hospitalizations. Particularly due to the risk of long QT syndrome.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

We strongly recommend systematizing electrocardiogram monitoring in all elderly patients admitted to the emergency department and treated with an antidepressant.     

PPI use in patients commenced on clopidogrel: a retrospective cross‐sectional evaluation

Background/Aims: Antiplatelet therapy with aspirin and clopidogrel is an important component of the management of acute coronary syndrome, but it also increases the risk of bleeding. There are no formal guidelines about the use of a proton pump inhibitor (PPI) for gastroprotection in patients on clopidogrel. This study assessed how many patients in the Royal Darwin Hospital (RDH) and the Royal Hobart Hospital (RHH) prescribed clopidogrel and at risk of bleeding were co‐prescribed PPIs. Methods: We conducted a retrospective cohort study using a pharmacy database to select all patients commenced on clopidogrel in a 1‐year period. We identified all patients newly prescribed clopidogrel and determined the proportion that had a risk factor for bleeding and also received a PPI. We also assessed the effect of the use of PPIs on the number of reported bleeds. Results: The final study cohort consisted of 385 patients who had been newly prescribed clopidogrel. Of all patients discharged on clopidogrel, 95·6% (368/385) had ≥1 risk factor for bleeding. One hundred and twenty‐eight of these patients [128/368, (34·8%)] were discharged on a PPI. Patients on dual antiplatelet therapy with an additional risk factor for bleeding and not discharged on a PPI were more likely to develop a major bleed than patients on dual antiplatelet therapy without a risk factor for bleeding not discharged on a PPI (11·1% vs. 1·8%; P < 0·01). Patients on dual antiplatelet therapy with an additional risk factor for bleeding not discharged on a PPI had a higher probability (borderline significance) of major bleeding, compared with patients on dual antiplatelet therapy with an additional risk factor for bleeding discharged on a PPI [PPI: 1/60, (1·7%) vs. no PPI: 6/54, (11·1%); P = 0·05]. Conclusions: Our results indicate that PPIs may only lower the probability of major bleeding in patients treated with dual antiplatelet therapy, who possess additional risk factor(s) for bleeding.     

Control of modifiable risk factors in ischemic stroke outpatients by pharmacist intervention: an equal allocation stratified randomized study

Objective: To evaluate the adequacy of management of modifiable risk factors (MRF) in a group of ischemic stroke outpatients and the value of pharmacist intervention in a randomized controlled study in a tertiary referral hospital. Methods: 160 ischemic stroke outpatients from the same catchment area and with the same financial arrangements for healthcare, went through a 6‐month equal allocation stratified randomized study. Routine practice was not altered except for a monthly 1‐hour pharmacist‐intervention education programme. We evaluated the differences in blood pressure (BP), blood glucose and lipid profiles before and after study. The proportion of patients with adequate management of MRF was studied. Results: There were no differences in the demographic characteristics, MRF and medications prescribed throughout the study. Before the study, the proportions of adequate control of BP in the control and intervention groups were 43% vs. 40% (P = 0·64), lipid 27% vs. 13% (P = 0·09) and glucose 36% vs. 21% (P = 0·15) . At the end of the study, the corresponding proportions were for BP 43% vs. 83% (P = 0·00), lipid 27% vs. 40% (P = 0·16) and glucose 46% vs. 35% (P = 0·40). Conclusion: Pharmacist intervention was associated with improved BP control but not with the other MRF. Earlier initiation and longer duration of intervention may improve the outcome further, and whether targeting of high‐risk subjects may be particularly rewarding is worthy of investigation.