Peter Loewen

The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.

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The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.

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Introduction: Heart failure with reduced ejection fraction (HFrEF) is a debilitating condition that can be managed with pharmacotherapy, consisting of an angiotensin receptor- neprilysin inhibitor (ARNI), a beta-blocker (BB), a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter-2 inhibitor (SGLT2I). However, the optimal process of initiating and titrating these medications, known as sequencing strategy, is widely debated. Methods and Results: A scoping review was conducted to identify ambulatory sequencing strategies for treatment-naïve, de novo HFrEF patients, revealing a trend in the selection of attributes from the identified strategies, with a focus on expediting the initiation of quadruple therapy. Two attributes were found to heavily influence this trend: the number of medications initiated during the first visit and whether to prioritize initiation or titration. Based on these attributes, we developed a framework to classify sequencing strategies into 3 strategy types, and proposed 2 profiles to represent each type. A benefit-harm and cost-utility analysis was performed using an individual-based state-transition microsimulation model, where each profile was modeled in 2 versions with medication adjustment made fortnightly (a) or weekly (b). Probabilistic analysis of 10,000 trials and 1,000 samples with a willingness-to-pay threshold of $50,000/QALY were conducted, along with one-way sensitivity analysis, and 2 scenario analyses. The analysis demonstrated that the incremental cost-effectiveness among the different strategies is minimal, favoring more intensive strategies after considering benefits, harms and costs. In the base scenario, “simultaneous” sequencing strategy with fortnightly adjustment (Profile 6a) was most likely to be cost-effective. However, in the scenario where sub-target doses were assumed to be ineffective, strategies involved weekly adjustment were more likely to be optimal compared to fortnightly adjustment. In the scenario where medication adjustments were stopped after 3 months, “traditional” sequencing strategy with fortnightly adjustment (Profile 1a) failed to achieve quadruple therapy, resulting in substantially fewer benefits.Conclusions: There was a noticeable trend towards prioritizing the speed of sequencing HFrEF quadruple therapy in the literature. However, this analysis revealed that the incremental cost-effectiveness among the different strategies was marginal. The key factor determining optimal outcomes was the successful establishment of patients on quadruple therapy within a reasonable timeframe.

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Introduction: Atrial fibrillation (AF) is the most common clinically significant heart arrhythmia. AF increases the risk of stroke or systemic embolism (SSE) by 3-5 times. Oral anticoagulants (OACs) reduce the risk of SSE in AF patients. Given the differing attributes of the five available OACs, the valuation or preferences of AF patients and the different timelines of approval of the OACs, switching is expected.Objective: To comprehensively describe OAC switching among Canadian patients with AF and to characterize the potential benefits of OAC switching using administrative health data.Methods: A scoping review was used to map the available evidence on OAC switching in patients with AF. To evaluate OAC switching, a longitudinal study was conducted using an established cohort of adult AF patients, using population-based administrative health data in British Columbia (BC). Switching was defined as a change from one OAC to another with ≤30 days gap between the prescriptions. The patterns of OAC switches and switchbacks for patients with more than one switch were characterized. Multivariable Cox regression was used to determine factors associated with OAC switching. A Delphi process was used to develop a taxonomy on the beneficial effects of OAC switching which was applied to information on OAC switching from the longitudinal study using administrative health data.Results: The scoping review revealed many gaps in the literature. Among the cohort of patients with AF in BC, OAC switching was common with 25% of patients in the cohort experiencing at least one switch. Up to 26% of patients on each OAC experienced a switchback to an OAC they had been on before. Stroke, heart failure and vascular disease had the highest hazards for switches between OAC classes. Potential safety, effectiveness, convenience, economic and, drug-interaction benefits to OAC switches were observed.Conclusion: I showed the extent of OAC switching in AF patients and the potential beneficial attributes. Apixaban is increasingly becoming the OAC to switch to. There are more convenience and drug-interaction benefits to OAC switches observed compared to effectiveness, safety and economic benefits. Findings may be useful in AF patient education, health policies, and OAC reimbursement criteria.

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Introduction: Education facilitates construction of a correct illness representation, corrects beliefs about medications and improves patients’ illness-treatment coherence. There is no consensus on the best education strategy for atrial fibrillation (AF) patients. Identifying patients’ education needs is the first step towards development of an effective education program.Purpose: The overall aim of this thesis was to provide insights into AF patients’ education needs from patient and clinician viewpoints, and to inform the design of AF patient education programs and initiatives.Methods: The current evidence on AF patients’ knowledge gaps was summarized through a literature review. This was followed by a qualitative descriptive study utilizing semi-structured interviews with patients and clinicians who were recruited through purposive sampling. All interviews were conducted by a Master of science student. The interviews were conducted in English, in a private room or over the phone, without the presence of any non-participants. Each interview lasted approximately 30 minutes and was audio-recorded. Verbatim transcripts were generated within three days of the interview. The reporting of this qualitative study conforms to the Standards for Reporting Qualitative Research (SQRQ) and the Consolidated Criteria for Reporting Qualitative Research (COREQ).Analysis: The analysis of the data was iterative, occurring as interviews proceeded. The interview guides were revised frequently based on the emerging data. The data collected were analyzed through inductive qualitative thematic analysis. Data from patients and clinicians were analyzed independently.Results: Eleven clinicians and ten patients were interviewed. Clinician and patient interviews led to emergence of three and four themes, respectively. This research went beyond identification of knowledge gaps by offering a rich description on patients’ misconceptions, information seeking behavior, education style preferences, attitudes towards online education, expectations of an education program, emotional education needs, preferences for risk communication, and clinicians’ views on the topic. A key finding of my study was the identification of patients’ emotional education needs: the need for education that addresses patients’ concerns and relieves their anxiety. Summarizing my study findings, I offered a set of recommendations that can be used by those involved in educating AF patients.

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