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Article: Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study.

Mackinnon, Erin S / Leiter, Lawrence A / Wani, Rajvi J / Burke, Natasha / Shaw, Eileen / Witges, Kelcie / Goodman, Shaun G

Cardiology and therapy

2024 Volume 13, Issue 1, Page(s) 205–220

Abstract: Introduction: The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on ... ...

Abstract	Introduction: The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Methods: Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. Results: The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). Conclusion: This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2700626-8
ISSN	2193-6544 ; 2193-8261
ISSN (online)	2193-6544
ISSN	2193-8261
DOI	10.1007/s40119-024-00349-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Correction to: Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i.

Mackinnon, Erin S / Har, Bryan / Champsi, Salimah / Wani, Rajvi J / Geyer, Lee / Shaw, Eileen / Farris, Megan S / Anderson, Todd J

Cardiology and therapy

2023 Volume 12, Issue 2, Page(s) 339

Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2700626-8
ISSN	2193-6544 ; 2193-8261
ISSN (online)	2193-6544
ISSN	2193-8261
DOI	10.1007/s40119-023-00310-z
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Article: Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i.

Mackinnon, Erin S / Har, Bryan / Champsi, Salimah / Wani, Rajvi J / Geyer, Lee / Shaw, Eileen / Farris, Megan S / Anderson, Todd J

Cardiology and therapy

2023 Volume 12, Issue 2, Page(s) 327–338

Abstract: Introduction: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the ... ...

Abstract	Introduction: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events. Here, we assess LDL-C levels and threshold achievement among patients by lipid-lowering therapies (LLT) received post-AMI. Methods: A retrospective cohort study of patients identified with AMI between 2015 and 2019 was conducted using administrative health databases in Alberta, Canada. Patients were grouped by their highest-intensity LLT post-AMI (proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT; PCSK9i alone; ezetimibe + statin; statins (high, moderate, low intensity); or ezetimibe alone), and available LDL-C levels were examined in the year before and after LLT dispense date. Results: The cohort included 15,283 patients. In patients on PCSK9i + LLT, the median [95% confidence interval (CI)] LDL-C levels decreased from 2.7 (2.3-3.4) before to 0.9 (0.5-1.2) mmol/l after treatment, the largest decrease among treatment groups. In the ezetimibe + statin and high-intensity statin groups, median (95% CI) values after treatment were 1.5 (1.5-1.6) and 1.4 (1.4-1.4) mmol/l, respectively. The proportion of patients below the 1.8 mmol/l threshold increased by 77.7% in the PSCK9i + LLT group after treatment, compared to 45.4 and 32.4% in the ezetimibe + statin and high-intensity statin groups, respectively. Conclusions: Intensification with PCSK9i in AMI patients results in a greater proportion of patients achieving below the recommended LDL-C threshold versus statins and or ezetimibe alone. Increased focus on achieving below the LDL-C thresholds with additional LLT as required may benefit patient cardiovascular outcomes.
Language	English
Publishing date	2023-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2700626-8
ISSN	2193-6544 ; 2193-8261
ISSN (online)	2193-6544
ISSN	2193-8261
DOI	10.1007/s40119-022-00300-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Trends in major adverse cardiac events and healthcare utilization during the COVID-19 pandemic in Alberta, Canada.

Mackinnon, Erin S / Anderson, Todd / Raggi, Paulo / Gregoire, Jean / Wani, Rajvi J / Packalen, Millicent S / Graves, Erin / Ekwaru, Paul / McMullen, Suzanne / Goodman, Shaun G

CJC open

2023

Abstract: Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in Canada. The COVID-19 pandemic altered the usual care of ambulatory and acute cardiac patients. This study aimed to describe ASCVD-related ... ...

Abstract	Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in Canada. The COVID-19 pandemic altered the usual care of ambulatory and acute cardiac patients. This study aimed to describe ASCVD-related clinical outcomes and healthcare resource utilization (HCRU) patterns during the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada, relative to the three preceding years. Methods: A repeated cross-sectional study design was conducted over three-month periods using administrative health data between March 15, 2017, and March 14, 2021. ASCVD-related clinical outcomes included major adverse cardiovascular events (MACE) endpoints. HCRU was assessed through general practitioner and other healthcare professional visits (including telehealth claims) for ASCVD events, emergency department visits, ASCVD diagnostic imaging tests, laboratory tests, and hospital length of stay. Results: Relative to the control year period (March to June 2019) ASCVD-related events (i.e., hospitalizations, emergency department (ED) visits and physician office visits) declined by 23% during the three-months COVID-19 period (March to June 2020). Acute declines were not sustained following June 2020. In contrast, in-patient mortality rates involving a primary MACE endpoint increased from March to June 2020 COVID-19 period. Conclusions: This study demonstrates the COVID-19 pandemic and corresponding public health restrictions impacted ASCVD-related care. While many clinical outcomes returned to pre-pandemic levels at the end of the observation period, our results suggest that patients' HCRU declined, which could lead to further CV events and mortality. Understanding the impact of COVID-19 restrictions on ASCVD-related care may help improve healthcare resiliency.
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2589-790X
ISSN (online)	2589-790X
DOI	10.1016/j.cjco.2023.06.004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.

Gupta, Milan / Wani, Rajvi J / Al Faraidy, Khalid / Bergeron, Jean / Contreras, Eduardo / Peña, Angel Alberto Garcia / Mancini, G B John / Padilla, Francisco / Lopez, Abel Alberto Pavia / Philip, Kiran / Wu, Johnny / Mackinnon, Erin S

Cardiology and therapy

2023 Volume 12, Issue 4, Page(s) 703–722

Abstract: Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries.: Methods: This retrospective and prospective observational study ... ...

Abstract	Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries. Methods: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available. Results: A total of 578 patients were enrolled (40.1% female, median age 60 [interquartile range (IQR) 51-68] years); 83.7% had atherosclerotic cardiovascular disease and/or familial hypercholesterolemia. Median low-density lipoprotein cholesterol (LDL-C) at baseline was 3.4 (IQR 2.7-4.2) mmol/L (131.5 [IQR 104.4-162.4] mg/dL), with 75.6% of patients receiving a statin (59.2% high intensity). Compared to baseline, the median lowest LDL-C was reduced by 70.2% and remained stable over 12 months of treatment. Guideline-recommended LDL-C thresholds < 1.8, < 1.4 and < 1.0 mmol/L (< 70, < 55 and < 40 mg/dL) were achieved by 75.3%, 63.6% and 47.4% of patients. LDL-C outcomes were consistent across high- and very high-risk patients. Background lipid-lowering therapy remained relatively stable. No serious treatment-emergent adverse events were reported, and persistence to evolocumab was 90.2% at 12 months. Conclusion: These findings provide real-world evidence that evolocumab use is in accordance with its international guideline-recommended place in dyslipidemia therapy, as well as confirmation of its effectiveness and safety in a heterogeneous population. Evolocumab can address a healthcare gap in the management of dyslipidemia by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.
Language	English
Publishing date	2023-10-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2700626-8
ISSN	2193-6544 ; 2193-8261
ISSN (online)	2193-6544
ISSN	2193-8261
DOI	10.1007/s40119-023-00334-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Increasing Prevalence and Incidence of Atherosclerotic Cardiovascular Disease in Adult Patients in Ontario, Canada From 2002 to 2018.

Mackinnon, Erin S / Goeree, Ron / Goodman, Shaun G / Rogoza, Raina M / Packalen, Millicent / Pericleous, Louisa / Motsepe-Ditshego, Ponda / Oh, Paul

CJC open

2021 Volume 4, Issue 2, Page(s) 206–213

Abstract: Background: Cardiovascular disease is the second-leading cause of death in Canada. However, limited data are available on the prevalence of atherosclerotic cardiovascular disease (ASCVD) in Canada. The study objective was to describe the incidence and ... ...

Abstract	Background: Cardiovascular disease is the second-leading cause of death in Canada. However, limited data are available on the prevalence of atherosclerotic cardiovascular disease (ASCVD) in Canada. The study objective was to describe the incidence and prevalence of ASCVD in adult patients in Ontario, Canada, and to evaluate temporal trends for subsequent ASCVD events among those with new-onset ASCVD. Methods: This retrospective, observational study identified ASCVD incidence and prevalence data from the Institute for Clinical Evaluative Sciences Data Repository for adults from Ontario. Overall prevalence was established for the period from 2002 to 2018. Incident cases from April 1, 2005 to March 2016 were then identified, and followed up to 2018. Primary outcomes were date and type of index event/procedure, patient characteristics/baseline demographics, and comorbidities. Secondary outcomes assessed were time from first to second ASCVD event, subsequent event(s) and/or mortality, and type of subsequent event(s) relative to the type of index/primary event. Results: A total of 1,042,621 eligible prevalent ASCVD cases were identified; of these, 743,309 patients (69%) were newly diagnosed with incident ASCVD. The 10-year prevalence rates for all ASCVD subtypes increased over the study period. Overall event incidence rates per 1000 person-years were mostly stable or increased. Among incident cases, 50% experienced subsequent events over the study period. Conclusions: This observational study demonstrated increasing prevalence and high incidence of new ASCVD diagnoses in adults from Ontario, over the study period. These data, together with the substantial number of subsequent events in ASCVD patients, demonstrate significant clinical burden of this disease in Ontario.
Language	English
Publishing date	2021-10-20
Publishing country	United States
Document type	Journal Article
ISSN	2589-790X
ISSN (online)	2589-790X
DOI	10.1016/j.cjco.2021.10.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study.

Gupta, Milan / Mancini, G B John / Wani, Rajvi J / Ahooja, Vineeta / Bergeron, Jean / Manjoo, Priya / Pandey, A Shekhar / Reiner, Maureen / Beltran, Johnny / Oliveira, Thiago / Mackinnon, Erin S

CJC open

2022 Volume 4, Issue 6, Page(s) 558–567

Abstract: Background: The 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) ... ...

Abstract	Background: The 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) concentration remains ≥ 1.8 mmol/L despite maximally tolerated statin therapy. This retrospective and prospective observational study characterizes Canadian patients treated with evolocumab and describes its effectiveness and safety. Methods: Between August 2017 and July 2019, a total of 131 patients initiated on evolocumab therapy were enrolled at 15 sites in Canada. Data were extracted from medical records every 3 months between 6 months prior to, and for 12 months following evolocumab therapy initiation, until July 6, 2020. Baseline and prospectively collected data are reported as available. Results: A total of 131 patients were enrolled (59.5% male; mean age [standard deviation (SD)] 64.7 ± 10.6 years), most with a diagnosis of atherosclerotic cardiovascular disease and/or familial hypercholesterolemia (93.4%). Mean (± SD) LDL-C concentration at baseline was 3.7 (± 1.7) mmol/L (n = 119), with 58.0% of patients receiving a statin (36.6% high intensity). Mean (± SD) LDL-C concentration after evolocumab treatment was 1.6 (± 1.0) mmol/L (n = 120), representing a 58.7% decrease from baseline (n = 109). This level remained stable over 12 months. An LDL-C concentration < 1.8 mmol/L was achieved by 77.5% of patients. Persistence was 92%, and no serious treatment-emergent adverse events were reported. Conclusions: These findings provide real-world evidence of guideline-recommended initiation of evolocumab therapy, as well as confirmation of its effectiveness and safety in a Canadian population. Evolocumab therapy can address a healthcare gap in the management of dyslipidemia, by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.
Language	English
Publishing date	2022-03-12
Publishing country	United States
Document type	Journal Article
ISSN	2589-790X
ISSN (online)	2589-790X
DOI	10.1016/j.cjco.2022.03.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Bone strength and management of postmenopausal fracture risk with antiresorptive therapies: considerations for women's health practice.

Cheung, Angela M / Frame, Heather / Ho, Michael / Mackinnon, Erin S / Brown, Jacques P

International journal of women's health

2016 Volume 8, Page(s) 537–547

Abstract: Bone strength - and, hence, fracture risk - reflects the structural and material properties of the skeleton, which changes with bone turnover during aging and following effective pharmacotherapy. A variety of powerful new techniques (quantitative ... ...

Abstract	Bone strength - and, hence, fracture risk - reflects the structural and material properties of the skeleton, which changes with bone turnover during aging and following effective pharmacotherapy. A variety of powerful new techniques (quantitative computed tomography, as well as peripheral quantitative computed tomography and high-resolution peripheral quantitative computed tomography) provide precise images of bone structure and can be used to model the response of specific bones to different types of mechanical load. This review explores the various components of bone strength and the clinical significance of measures, such as bone mineral density, bone turnover markers, and modern imaging data, with regard to fracture risk in women with postmenopausal osteoporosis, before and after initiating antiresorptive therapy. These imaging and related techniques offer an ever-clearer picture of the changes in bone structure and bone mineral metabolism during normal aging and in osteoporosis, as well as in response to treatment. However, because the newer techniques are not yet available in routine practice, validated tools for absolute fracture risk assessment remain essential for clinical decision making. These tools, which are tailored to patient risk data in individual countries, are based on bone mineral density and other readily available clinical data. In addition, bone turnover marker measurements can be useful in assessing risk and guiding treatment decisions for women with postmenopausal osteoporosis. Such tests may be used before starting a patient on antiresorptive therapy and for ongoing monitoring of treatment effectiveness.
Language	English
Publishing date	2016-09-28
Publishing country	New Zealand
Document type	Review ; Journal Article
ZDB-ID	2508161-5
ISSN	1179-1411
ISSN	1179-1411
DOI	10.2147/IJWH.S112621
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Article ; Online: Effect of cell-based VEGF gene therapy on healing of a segmental bone defect.

Li, Ru / Stewart, Duncan J / von Schroeder, Herbert P / Mackinnon, Erin S / Schemitsch, Emil H

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2009 Volume 27, Issue 1, Page(s) 8–14

Abstract: Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the ... ...

Abstract	Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p < 0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits.
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Cell Proliferation ; Cell Survival ; Dermis/metabolism ; Fibroblasts/metabolism ; Fracture Healing ; Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors ; Neovascularization, Pathologic ; Osteogenesis ; Rabbits ; Tibia/metabolism ; Tibia/pathology ; Tomography, X-Ray Computed/methods ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2009-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.20658
Database	MEDical Literature Analysis and Retrieval System OnLINE

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