Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study.

BACKGROUND: Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 inflammation markers in patients with moderate to severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. OBJECTIVE: To investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting ß2-agonist combination FF/VI, or doubling the FF dose. METHODS: Prespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire]) following addition of UMEC to FF/VI or doubling the FF dose in FF/VI or FF/UMEC/VI. RESULTS: Adding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling the FF dose across all baseline characteristics assessed. Doubling the FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling the FF dose generally led to improvements in Asthma Control Questionnaire scores irrespective of baseline characteristics. CONCLUSIONS: Unlike previous findings with type 2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.

Real-world users of triple therapy for asthma in the US.

OBJECTIVES: For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting ß2 agonist, addition of a long-acting muscarinic antagonist as a supplementary controller is a recommended option. However, real-world data on the characteristics and treatment patterns of these patients are limited. This study described the demographics and clinical characteristics of new users of single- or multiple-inhaler triple therapy and treatment patterns preceding triple-therapy initiation. STUDY DESIGN: This retrospective cohort study used medical and pharmacy claims data from the IQVIA PharMetrics Plus database. METHODS: The study population comprised adults with asthma with or without chronic obstructive pulmonary disease (COPD) initiating triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 µg) or multiple-inhaler triple therapy (MITT) between September 18, 2017, and September 30, 2019. Demographics, clinical characteristics, and treatment patterns in the 12 months preceding triple-therapy initiation were described (baseline period). RESULTS: A total of 12,395 patients were included. Among FF/UMEC/VI initiators with asthma (n = 1301), the mean age was 49.0 years and 59.3% were women. During the baseline period, 81.5% of patients used controller therapy, 94.7% used rescue medications, and 42.0% reported at least 1 asthma-related exacerbation; the annual mean exacerbation rate was 0.96. Similar trends were observed among patients with asthma initiating MITT and patients with comorbid asthma-COPD initiating FF/UMEC/VI or MITT. CONCLUSION: In real-world practice, triple therapy is often utilized following other asthma controller medication use. High disease burden, as evidenced by substantial use of rescue medications and continued asthma-related exacerbations, suggests that patients may not have achieved adequate asthma control prior to triple-therapy initiation.

Changes in Oral Corticosteroid Utilization in Patients with COPD Following Initiation of FF/UMEC/VI.

Purpose: Oral corticosteroids (OCS) play a role in the treatment of acute chronic obstructive pulmonary disease (COPD) exacerbations; however, chronic use is not recommended due to the high rate of systemic complications, development of comorbidities, and increased mortality. Data assessing the real-world impact of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) on OCS utilization rates are limited. This study assessed the impact of FF/UMEC/VI on OCS use among patients with COPD previously treated with OCS. Patients and Methods: A retrospective database study of patients with COPD aged ≥40 years who initiated FF/UMEC/VI from 1 November 2017 to 31 December 2018, identified through the MarketScan® Commercial and Medicare Supplemental databases. Patients were required to have ≥1 dispensing of an OCS prior to initiation of FF/UMEC/VI (index) and were followed up for 12 months post-index. OCS utilization patterns, potential OCS-related adverse events, healthcare resource utilization (HCRU), and costs were compared between the 12-month pre- and post-index periods. Results: A total of 2013 patients were identified (mean age 63.5 years, 55.7% female). The proportion of patients with ≥1 OCS claim decreased by 32.2% between the pre- and post-index period (67.8% vs 100%; p < 0.001). Comparing the post-index period to the pre-index period, mean number of OCS pharmacy claims per patient decreased from 3.3 to 2.5 (p < 0.001) and mean daily dose was reduced from 3.1 to 2.6 mg/day (p = 0.004); 30.0% of patients reduced their daily dose by 90-100%. Reductions were also seen in COPD-related HCRU. The proportion of patients with an inpatient admission for COPD decreased from 11.4% to 7.1% (p < 0.001), emergency room visits decreased from 23.1% to 17.4% (p < 0.001), and office visits from 97.5% to 90.1% (p < 0.001). Similar results were seen for all-cause HCRU. Conclusion: Among patients with COPD with prior OCS use, FF/UMEC/VI initiation resulted in significant reductions in OCS utilization, COPD-related HCRU (including hospitalization), and all-cause HCRU.

Adherence and Persistence to Single-Inhaler Versus Multiple-Inhaler Triple Therapy for Asthma Management.

BACKGROUND: Treatment guidelines recommend triple therapy for patients with asthma who remain uncontrolled on inhaled corticosteroid/long-acting ß2-agonist therapy. Previously, triple therapy was only available via multiple inhalers. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) is approved as maintenance treatment for asthma; however, real-world information on adherence and persistence is limited. OBJECTIVE: To compare adherence and persistence among adult patients with asthma receiving single-inhaler FF/UMEC/VI versus multiple-inhaler triple therapy (MITT) in the United States. METHODS: This retrospective cohort study used IQVIA PharMetrics Plus data to evaluate patients with asthma who initiated once-daily FF/UMEC/VI 100/62.5/25 mcg or MITT between September 18, 2017, and September 30, 2019. Inverse probability weighting and multivariable regression adjusted for differences in characteristics between the FF/UMEC/VI and MITT cohorts. Adherence was assessed using proportion of days covered (PDC) and proportion of patients achieving PDC ≥0.8 and PDC ≥0.5. Non-persistence was identified as a >45-day gap between fills. RESULTS: The study included 1396 FF/UMEC/VI and 5115 MITT initiators. Three months after initiation, FF/UMEC/VI users had significantly higher mean PDC versus MITT users (0.68 vs 0.59; P < .001) and 31% more likely to be adherent (PDC ≥0.8; 40.6% vs 31.3%; adjusted risk ratio [95% confidence interval (CI)]: 1.31 [1.13-1.54]; P < .001). Similar patterns were observed at 6 and 12 months post initiation. In addition, FF/UMEC/VI users were 49% more likely to persist at 12 months than MITT users (25.9% vs 15.1%, adjusted hazard ratio [95% CI]: 1.49 [1.39-1.60]; P < .001). CONCLUSIONS: Patients with asthma initiating triple therapy with FF/UMEC/VI had significantly better adherence and persistence compared with MITT initiators.

Orofacial rehabilitation with zygomatic implants: CAD-CAM bar and magnets for patients with nasal cancer after rhinectomy and partial maxillectomy.

Nasal carcinoma extending into the premaxilla requires radical surgical excision including rhinectomy and partial maxillectomy. Rehabilitation is complex and involves the use of removable prostheses. Three patients treated with zygomatic implants and custom-milled bars to retain an obturator and nasal prosthesis are presented.

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 1--blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on appropriate blood pressure measurement, the timely assessment of serially elevated readings, the degree of blood pressure elevation, the method of measurement (office, ambulatory, home) and associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk and determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2007 to October 2008 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Key messages include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of global risk assessment and the need for ongoing monitoring of hypertensive patients to identify incident type 2 diabetes. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.

The 2008 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 1 - blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on appropriate blood pressure measurement, the timely assessment of serially elevated readings, degree of blood pressure elevation, method of measurement (office, ambulatory, home) and associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk and determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2006 to October 2007 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed, full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Key messages in 2008 include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of global risk assessment and the need for ongoing monitoring of hypertensive patients to identify incident type 2 diabetes. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here received at least 70% consensus. These guidelines will continue to be updated annually.

The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 1- blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on the appropriate measurement of blood pressure, the timely assessment of serially elevated readings, the degree of blood pressure elevation, the method of measurement (office, ambulatory, home) and any associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk, and to determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2005 to October 2006 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed, full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Key messages in 2007 include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of assessing the risk of cerebrovascular events as part of global risk assessment, the need for ongoing reassessment of patients with high normal blood pressure, and reviews of recent studies involving laboratory testing and home monitoring. VALIDATION: All recommendations were graded according to strength of the evidence and were voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here received at least 70% consensus. These guidelines will continue to be updated annually.

The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I--Blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with high blood pressure. OPTIONS AND OUTCOMES: For persons in whom a high blood pressure value is recorded, a diagnosis of hypertension is dependent on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the approach used to monitor blood pressure (office, ambulatory or home/self), and the duration of follow-up. In addition, the presence of cardiovascular risk factors and target organ damage should be assessed to determine the urgency, intensity and type of treatment. For persons diagnosed as having hypertension, estimating the overall risk of adverse cardiovascular outcomes requires an assessment for other vascular risk factors and hypertensive target organ damage. EVIDENCE: MEDLINE searches were conducted from November 2004 to October 2005 to update the 2005 recommendations. Reference lists were scanned, experts were polled, and the personal files of the authors and subgroup members were used to identify other studies. Identified articles were reviewed and appraised using prespecified levels of evidence by content and methodological experts. As per previous years, the authors only included studies that had been published in the peer-reviewed literature and did not include evidence from abstracts, conference presentations or unpublished personal communications. RECOMMENDATIONS: The present document contains recommendations for blood pressure measurement, diagnosis of hypertension, and assessment of cardiovascular risk for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, and the role of echocardiography for those with hypertension. Key features of the 2006 recommendations include continued emphasis on an expedited diagnosis of hypertension, an in-depth review of the role of global risk assessment in hypertension therapy, and the use of home/self blood pressure monitoring for patients with masked hypertension (subjects with hypertension who have a blood pressure that is normal in clinic but elevated on home/self measurement). VALIDATION: All recommendations were graded according to the strength of the evidence and were voted on by the 45 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported herein received at least 95% consensus. These guidelines will continue to be updated annually.

The 2005 Canadian Hypertension Education Program recommendations for the management of hypertension: part 1- blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with high blood pressure (BP). OPTIONS AND OUTCOMES: For persons in whom a high BP value is recorded, the assignment of a diagnosis of hypertension is dependent on the appropriate measurement of BP, the level of the BP elevation and the duration of follow-up. In addition, the presence of cardiovascular risk factors and target organ damage should be assessed to determine the urgency, intensity and type of treatment. For persons diagnosed as having hypertension, estimating overall risk of adverse cardiovascular outcomes requires an assessment of other vascular risk factors and hypertensive target organ damage. EVIDENCE: MEDLINE searches were conducted from November 2003 to October 2004 to update the 2004 recommendations. Reference lists were scanned, experts were polled, and the personal files of the authors and subgroup members were used to identify other studies. Identified articles were reviewed and appraised using prespecified levels of evidence by content and methodological experts. As per previous years, only studies that had been published in the peer-reviewed literature were included; evidence from abstracts, conference presentations and unpublished personal communications was not included. RECOMMENDATIONS: This document contains recommendations for BP measurement, diagnosis of hypertension and assessment of cardiovascular risk for adults with high BP. These include the accurate measurement of BP, criteria for diagnosis of hypertension, and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory BP monitoring, and the role of echocardiography for those with hypertension. Key features of the 2005 recommendations include an expedited diagnostic algorithm for hypertension and an endorsement of the use of home/self and ambulatory BP assessment as validated techniques in establishing the diagnosis of hypertension. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the 43 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported in the present paper received at least 95% consensus. These guidelines will continue to be updated annually.

Hormone replacement use, arterial distensibility, cardiac structure and circadian blood pressure profile in menopausal women.

Observational and interventional studies that evaluate the impact of hormone replacement therapy (HRT) on cardiovascular changes have produced inconsistent and inconclusive results. The present study sought to elucidate the influence of HRT on aortic distensibility, left ventricular mass (LVM) and 24-h blood pressure (BP) profile in 38 menopausal women who were either HRT users or non-users. The two groups were similar for age, ambulatory BP, aortic distensibility, cardiac mass, lipid profile and body mass index but differed in clinic diastolic BP (DBP). HRT non-dippers had significantly lower clinic and daytime DBP and a smaller nocturnal BP reduction than dippers. Daytime DBP was significantly and inversely related to duration of HRT use. The present study demonstrates that hormonal therapy after menopause lowers DBP, but shows no significant influence on aortic distensibility, cardiac mass or 24-h BP profile. HRT users who were dippers demonstrated a significantly greater nocturnal BP reduction. Long-term controlled trails are needed to better define the effects of estrogen and progestin on the aorta, the heart and 24-h BP profile in normotensive and hypertensive menopausal women.

The 2001 Canadian recommendations for the management of hypertension: Part one--Assessment for diagnosis, cardiovascular risk, causes and lifestyle modification.

OBJECTIVE: To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure. OPTIONS: For persons in whom a high blood pressure value is recorded, hypertension is diagnosed based on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases must be assessed to determine the urgency, intensity and type of treatment. For persons receiving a diagnosis of hypertension, defining the overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: The outcomes were: the identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension. EVIDENCE: Medline searches were conducted from one year before the period of the last revision of the Canadian recommendations for the management of hypertension (May 1999 to May 2001). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. In addition to an update of the previous year's review, new sections on assessing overall cardiovascular risk and endocrine causes are provided. VALUES: A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and of persons with identifiable causes of hypertension. BENEFITS, HARMS AND COSTS: The identification of persons at higher risk of cardiovascular disease will permit counseling for lifestyle manoeuvres and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. In certain subgroups of patients, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity or mortality. RECOMMENDATIONS: The present document contains recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, the role of echocardiography and lifestyle modifications. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported. These guidelines will be updated annually. ENDORSEMENT: These guidelines are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control, Health Canada.