Month: August 2016

Adverse drug events (ADE) are common in emergency departments and acute care hospitals but are poorly documented in electronic medical records and administrative data. This increases the likelihood of recurrence due to lack of information continuity between providers and across health sectors. The objective of this query is to determine the preventability of an ADE, identify contributing factors, determine the ADE-related harm and interventions required, and identify the kind of drug re-exposure that would likely cause a future repeat ADE.

In Phase 1 of the query, a retrospective chart review of 1,234 patients found 1,356 ADEs with the majority being from adverse drug reactions and non-adherence. 64%of ADEs were determined to be preventable and 29% were repeat events. Certain drugs, inadequate patient counselling, lack of follow-up after a change in the regimen, mental health diagnoses, diabetes, and a prior ADE to the same drug were associated with patients having preventable ADEs. Diabetes and renal failure were significant in association with patients having repeat ADEs.

In Phase 2, phase I data was linked to BC health data (PharmaNet) to determine the proportion of ADE patients that were re-exposed to contraindicated medications. 

Future work will involve survival analysis regression to examine risk factors for the hazard of re-exposure by modeling the time-to-re-dispensation

Woo SA, Cragg A, Wickham ME, Peddie D, Balka E, Scheuermeyer F, Villanyi D, Hohl CM. Methods for evaluating adverse drug event preventability in emergency department patients. BMC Red Res Methodol. 2018;18:160.

Hohl CM, Woo SA, Cragg A, Wickham ME, Ackerley C, Scheuermeyer F, Villanyi D. Repeat adverse drug events associated with outpatient medications: a descriptive analysis of 3 observational studies in British Columbia, Canada. CMAJ Open. July 2019;7(3):E446-53.

Woo SA, Cragg A, Wickham ME, Villanyi D, Scheuermeyer F, Hau JP, Hohl C. Preventable adverse drug events: Descriptive epidemiology. Br J Clin Pharmacol. 2020 Feb;86(2):291-302. 

Hohl et al. Repeat exposures to culprit drugs contribute to adverse drug events in emergency department patients. 2017 (CAEP abstract).

Hohl et al. Preventable adverse drug events in Canadian emergency departments. 2017 (CAEP abstract).

Woo et al. Factors contributing to the development of adverse drug events treated in emergency departments. 2017 (CAEP abstract).

Wickham et al. Preventable and repeat adverse drug events in Canadian emergency department patients. 2017 (CAHSPR abstract).

Woo et al. Preventable adverse drug events in Canadian emergency departments. 2019 (CAEP abstract).

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research is funded by CIHR-DSEN 
Lead investigator: Dr. Corinne Hohl
Query 16-03 raised by Health Canada

Query 15-11: Intravitreal bevacizumab for retinal conditions: a real-world safety assessment.

 

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Sasha Bernatsky, Cristiano Moura, Robert Campbell, Marina Machado, Hassan Behlouli.

Issue:

• Age-related macular degeneration (AMD) is one of the leading causes of blindness among older Canadians, leading to severe disability. Anti-vascular endothelial growth factor (anti-VEGF, e.g., bevacizumab) agents have dramatically changed the management of neovascular AMD and other retinal conditions.
• Drug‐related adverse events associated with anti-VEGF agents have been reported, but there is a paucity of real-world safety data.
• This study examined ocular and systemic complications of anti-VEGF injections given for neovascular (‘wet’) AMD and other serious retinal conditions, using population-based cohorts.

Study aim:

• We studied the safety of bevacizumab when injected intravitreally for the treatment of patients threatened with the following causes of serious vision loss:

1. neovascular (wet) AMD;
2. diabetic macular edema;
3. macular edema due to retinal vein occlusion;
4. choroidal neovascularization secondary to pathologic myopia.

Study description:

• The first cohort study used previously validated International Classification of Diseases (ICD) diagnostic codes to identify the above diagnoses of interest within the United States Marketscan Commercial Claims administrative health database (2011-2016).
• The second study used drug codes to identify a treatment-based cohort of anti-VEGF users within the National Prescription Drug Utilization Information System, NPDUIS (2012-2016).
• In all analyses, we used time-to-event analyses of safety outcomes, including.

1. Local complications (endophthalmitis, rhegmatogenous retinal detachment, retinal tear, uveitis, glaucoma, and vitreous hemorrhage)
2. Systemic complications (stroke, heart attack, deep vein thrombosis, and pulmonary embolism).

Study findings:

• The current use of any anti-VEGF (versus no current use) was associated with a higher risk of both local and systemic complications.
• In the direct comparisons of different anti-VEGF agents, we found a greater risk of local complications for bevacizumab versus ranibizumab in patients with diabetic retinal conditions. We also noted a higher risk of uveitis for aflibercept versus ranibizumab in AMD patients and a lower risk of vitreous hemorrhage when comparing the same agents in patients with AMD and diabetic retinal conditions.
• No clear differences were seen in systemic complications, comparing anti-VEGF agents with each other.
• These drugs, which hold promise to prevent or delay blindness for millions of Canadians, are associated with relatively low rates of systemic complications, which did not differ amongst the different agents. However, differences in the profile of local complications were noted for some anti-VEGF agents.

Summary:

• Age-related macular degeneration (AMD) is a leading cause of blindness and may affect up to 3.2% of Canadians. Our objective was to examine anti-VEGF agents’ safety when injected intravitreally as the treatment of AMD or other retinal conditions.
• The current study’s results support prior findings, suggesting that different anti-VEGF agents have similar safety profiles regarding systemic effects (stroke, heart attack, deep vein thrombosis, pulmonary embolism).
• We did find a greater risk of ocular adverse outcomes for bevacizumab versus ranibizumab or aflibercept versus ranibizumab in some instances.
• We evaluated the risk associated with current exposure of anti-VEGF agents, examined as both therapeutic class and individual drugs, on primary and secondary outcomes in Marketscan data (2011-2015).
• We also presented the AMD cohort’s updated results for anti-VEGF agents examined as individual drugs, using one additional year of MarketScan data (2011-2016) in a report to DSEN in July 2018.
• We presented these alongside results from one previously published population-based nested case-control study using health care data sets in Ontario (April 2006-March 2011) comparing serious adverse events between bevacizumab and ranibizumab.
• We noted that bevacizumab was widely used in Ontario before public formulary coverage through the Ontario Drug Benefit (ODB) program.
• The use of bevacizumab for retinal diseases has become negligible in Ontario among patients 65 years of age, and older (ODB eligible population) since the initiation of coverage within the ODB formulary for the Health Canada approved drug ranibizumab.

A webinar to present final results was held in October 2019.

Moura et al. Safety of anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections for the treatment of patients with age-related macular degeneration (AMD). 2017 (ICPE abstract)

Machado et al. Safety of intravitreal injections for the treatment of patients with diabetic retinopathy: a population-based study. 2017 (ICPE abstract)

Full report submitted to DSEN and query submitters.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

Query 11-03: How do thiazide diuretics compare to ACE inhibitors and combination antihypertensive products in terms of effectiveness (and cost-effectiveness) for the management of hypertension in non-diabetic patients?

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Cristiano S Moura, Sasha Bernatsky, Michal Abrahamowicz, Louise Pilote and the CAN-AIM team.

Issue:

• Pharmacological treatment that controls blood pressure can reduce morbidity and mortality in hypertensive patients; however, gaps remain regarding the best approaches.
• Thiazide diuretics (TD) are cheaper than other antihypertensive classes and have great potential for saving costs when used first-line hypertension.

Study aim:

• This study aimed to compare TD with other antihypertensive, including angiotensin-converting enzyme (ACE) inhibitors, used as monotherapy for hypertension in non-diabetic patients.

Study description:

• CAN-AIM conducted one cross-sectional analysis with data from a Canadian population-based study and two longitudinal analyses from international databases.
• CAN-AIM investigators conducted a comprehensive comparison between TD and three other classes of antihypertensive (ACE inhibitors, angiotensin receptor blocker [ARB], and calcium-channel blockers [CCB]) in terms of peripheral and central blood pressure measurements, therapy persistence, and clinical outcomes (cardiovascular and cerebrovascular fatal and non-fatal events).

Study findings:

• Most patients who started with monotherapy treatment for hypertension do not stay long on the monotherapy regimen. Patients starting on TD were more likely to discontinue or add a new antihypertensive medication compared with initiators of ACEi or ARB.
• Patients using TDs were similar to non-TD users in terms of central blood pressure measurements. Over a 12-month period, the use of TDs was associated with a clinically significant reduction of systolic blood pressure when compared to ACEi and ARBs (8.3 mmHg reduction in the TD group compared to 6.3 and 2.6 in the ACEi and ARB groups, respectively).
• TD users exhibited a lower risk of cardiovascular and cerebrovascular events compared with ACEi and CCB users; patients using ACEi were 69% more likely to have these events when compared to TD users (among CCB users the risk was 74% higher). This association was clearer in women than in men.

Summary:

• Hypertensive patients using TDs in monotherapy are more likely to discontinue or initiate a new treatment, but those who remain on TD have a greater reduction in their blood pressure compared to ACEi and ARB and lower risk of cardiovascular and cerebrovascular outcomes when compared to ACEi and CCB. This later result is more clearly seen in women than in men, in part due to our limited power in males.
• Our results bring evidence from real-world population and support prior findings that TDs are effective in treating hypertension in non-diabetic adults. Considering our results and the low cost of the medication, TDs are the most rational first-line choice in treating hypertension in non-diabetic adults, especially in women.

Machado et al. Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population-based study. J Clin Hypertens (Greenwich). 2017 Oct;19(10):999-1009.

Moura et al. Comparison of the Effect of Thiazide Diuretics and Other Antihypertensive Drugs on Central Blood Pressure: Cross-Sectional Analysis Among Nondiabetic Patients; J Clin Hypertens. 2015;17:848–854

Moura et al. Hypertension treatment and cross-sectional relationship with peripheral and central blood pressure in non–diabetic participants from the CARTaGENE Cohort Study. 2014. (CAPT abstract)

Machado MAA et al. Comparative effectiveness of thiazide diuretics and other monotherapies for nondiabetic individuals with hypertension. 2016. (CAPT abstract)

For more information, contact: Autumn Neville, Research Coordinator. [email protected]