Self-reported adherence to direct oral anticoagulants versus warfarin therapy in a specialized thrombosis service-a cross-sectional study of patients in a Canadian Health Region.

PURPOSE: Direct oral anticoagulants (DOACs) have a better safety and efficacy profile than warfarin and are currently recommended for stroke prevention in non-valvular atrial fibrillation (AF) and treatment of venous thromboembolism (VTE). Given that DOACs do not require regular laboratory monitoring compared to warfarin, patients' interactions with the health care system is reduced. Adequate adherence to DOACs is important and reported adherence to anticoagulation is unclear in clinical practice. This study aims to assess self-reported adherence to oral anticoagulants in a specialized Adult Outpatient Thrombosis Service (TS).  METHODS: This cross-sectional study included patients aged ≥ 18 years who were prescribed an oral anticoagulant and had attended at least one appointment with an Adult Outpatient Thrombosis Service (TS) between October 10, 2017, and May 31, 2019. Adherence to oral anticoagulant therapy was assessed using the 12-item validated Adherence to Refills and Medications Scale (ARMS) score. Logistic regression analyses were used to evaluate association between patient characteristics and medication adherence. Adherence rates in DOACs and warfarin were compared. RESULTS: Three hundred and ninety-nine patients completed and returned the survey. Of the 399 who completed the survey, 74% were prescribed DOACs and 26% received warfarin. Most of the patients (89.3%) were ≥ 50 years of age and half (57.3%) were male. About two-thirds (67%) had at least post-secondary education. The duration of anticoagulation use differed between patients on DOAC and warfarin; a greater proportion of those who had used anticoagulants for less than 1 year was on DOACs compared to warfarin (20.9% vs 4.9%, p = 0.001). For patients who had been on anticoagulation for > 5 years, the proportion of warfarin patients was greater than DOAC (57.8% vs 20.5%, p = 0.001). Self-reported adherence to oral anticoagulant therapy using the 12-item ARMS scale for warfarin and DOACs were 87.3% and 90.9%, respectively. Among the warfarin users, patient satisfaction with TS was associated with medication adherence (OR = 0.22; 95% CI: 0.05-0.89). CONCLUSIONS: Self-reported medication adherence was similar between warfarin and DOACs. Since suboptimal adherence is associated with poor clinical outcomes and increased costs, various stakeholders should emphasize the importance of medication adherence to oral anticoagulants at each patient encounter.

Association Between Medication Adherence and Risk of COPD in Adult Asthma Patients: A Retrospective Cohort Study in Canada.

Background: Poor adherence to prescribed asthma medications and risk of severe asthma exacerbations have been well established. However, the effects of changes in asthma medication compliance levels and subsequent risk of COPD is unknown and yet to be investigated. This study investigated the independent effect of medication adherence (MA) and asthma severity levels on the risk of COPD. Methods: We used four linked administrative health databases from the Population data BC to identify asthma patients aged 18 years and older between January 1, 1998 and December 31, 1999 without diagnosis of COPD. The primary event was time-to-COPD diagnosis during the follow-up period (January 1, 2000 to December 31, 2018). The proportion of days covered (PDC) - was used as a surrogate measure for medication adherence (MA) assessed at optimal-level (≥ 0.80), Intermediate-level (0.50-0.79), and low-level (< 0.5) of adherence. A propensity adjusted analysis with Marginal Structural Cox (MSC) model was employed to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for the effect of medication adherence and asthma severity over time. Results: At cohort entry, the sample included 68,211 asthma patients with an overall mean age of 48.2 years. The 18-year incidence of COPD in asthma patients was 9.8 per 1000-persons year. In an inverse weighted propensity adjusted analysis of the MSC model, higher MA levels were significantly associated with decreased risk of COPD as follows: optimal-level (aHR: 0.19, 95% CI: 0.17-0.24); Intermediate-level (aHR: 0.20, 95% CI: 0.18, 0.23) compared to the low-level adherence group. A significant increase in COPD risk was observed in severe asthma patients with low medication adherence (aHR: 1.72, 95% CI: 1.52-1.93), independent of other patient factors. Conclusion: Optimal (≥ 0.80) and intermediate adherence (0.5 to 0.79) levels were associated with reduced risk of COPD incidence over time. Interventions aimed at improving adherence to prescribed medications in adult asthma patients should be intensified to reduce their risk of COPD.

Effectiveness and safety of statins on outcomes in patients with HIV infection: a systematic review and meta-analysis.

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508-0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561-1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564-1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031-2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770-2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457-2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605-4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

Adherence to Antithrombotic Therapy for Patients Attending a Multidisciplinary Thrombosis Service in Canada - A Cross-Sectional Survey.

Background: Poor medication adherence puts patients who require antithrombotic therapy at greater risk of complications. We started a multidisciplinary Adult Outpatient Thrombosis Service in 2017 in a Canadian health authority and were interested in the level of medication adherence in the population attending. AimS: The aim of this study is to assess adherence to antithrombotic medications for patients attending a multidisciplinary Thrombosis Service. Methods: We conducted a cross-sectional survey of outpatients seen at the Thrombosis Service between 2017 and 2019 using the 12-item validated Adherence to Refills and Medications Scale (ARMS) to assess adherence to antithrombotic (anticoagulants and antiplatelet) therapy. Linear regression analysis examined the factors associated with adherence to antithrombotic therapy. Results: Of 1058 eligible patients, 53.2% responded to the survey. Seventeen were excluded from the analysis for missing more than 6 responses to the 12 items on the ARMS. About 55% (n = 297) were on direct oral anticoagulants (DOACs), 19% (n = 102) on warfarin, 5.0% (n = 27) on low molecular weight heparin, 3.3% (n = 18) on antiplatelet therapy and 18% (n = 96) were no longer on antithrombotic therapy. Nearly half (47%, n = 253) had taken antithrombotic therapy for 1-5 years while 28% (n = 150) and 25% (n = 137) had taken antithrombotic treatments for <1 and >5 years, respectively. Most patients (87%, n = 475) were ≥50 years and half (51%, n = 277) were male. The mean adherence score was 13.9 (SD±2.2) and 88% (n = 481) of participants were adherent to antithrombotic treatment (ARMS = 12-16). Multivariable linear regression showed that patients with post-graduate education had 0.4% lower adherence to antithrombotic therapy as compared with elementary education (ß = 0.0039, p = 0.048). Patients with prior antithrombotic agent use >5 years had 0.5% lower adherence to antithrombotic treatment compared to patients with <1 year (ß = 0.0047, p = 0.0244). Conclusion: Self-reported adherence to antithrombotic therapy was high (88%) within a multidisciplinary Thrombosis Service. Patients with advanced education and prolong duration of antithrombotic therapy were more likely to have lower self-reported adherence to antithrombotic treatment.

Assessment of a Pharmacist-Led Direct Oral Anticoagulant Monitoring Clinic.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as first-line therapy for treatment and prevention of venous thromboembolism (VTE) and prevention of stroke related to nonvalvular atrial fibrillation. Recent publications have suggested incorporating DOAC monitoring into anticoagulant management clinics. The Eastern Health Adult Outpatient Thrombosis Service (Newfoundland and Labrador) includes a pharmacist-led DOAC monitoring clinic that uses standardized evidence-based care processes. OBJECTIVES: To describe a new pharmacist-led DOAC monitoring clinic and to assess patients' adherence to medication therapy, adherence to guideline-recommended frequencies for blood work, and adverse and non-adverse events. METHODS: This retrospective chart review involved patients who attended their first visit to the DOAC clinic between October 10, 2017, and May 31, 2018. Patients were followed until November 30, 2018. Data were abstracted from electronic hospital records and the provincial pharmacy network. Descriptive statistics were used to analyze the data: categorical variables were presented as frequencies and percentages; continuous variables were analyzed and presented as means with standard deviations and, where applicable, as medians with interquartile ranges. RESULTS: Forty-seven patients, who attended a total of 74 clinic visits, were included. Twenty-eight patients (60%) were adherent to their DOAC therapy. All patients had blood work completed before each clinic appointment. The mean time between the first and second sets of blood tests was 6.2 (standard deviation [SD] 1.4) months and between the second and third sets of blood tests was 5.1 (SD 1.0) months. There were no episodes of VTE or major bleeding. There was 1 cerebrovascular accident (3.2 events per 100 person-years, 95% confidence interval [CI] 0.2-15.7) and 5 episodes of clinically relevant non-major bleeding (12.8 events per 100 person-years, 95% CI 4.1-30.1). Pharmacists identified 51 issues at the clinic appointments, of which 48 were medication-related. Referral to the Thrombosis Service physician was required to resolve 8 (16%) of the issues identified. A brief discussion between the Thrombosis Service physician and pharmacist was required to resolve 30 (59%) of the issues, with 13 (25%) resolved by the pharmacist alone. CONCLUSIONS: This study described the implementation and outcomes of a novel pharmacist-led DOAC clinic. Clinic patients underwent blood work at recommended intervals and received guidance on adherence and adverse events; as such, patients had follow-up that aligned with guideline recommendations.

CONTEXTE: Les anticoagulants oraux directs (AOD) sont recommandés comme thérapie de première ligne pour le traitement et la prévention de la thromboembolie veineuse (TEV) et la prévention des AVC liés à la fibrillation auriculaire non valvulaire. Des publications récentes ont proposé d'incorporer le contrôle des AOD dans les cliniques des anticoagulants. L'Eastern Health Adult Outpatient Thrombosis Service (St John's, Terre-Neuve-et-Labrador) comprend une clinique de surveillance des AOD, dirigée par des pharmaciens qui utilisent des processus de soins standardisés basés sur des éléments de preuve. OBJECTIFS: Décrire une nouvelle clinique de surveillance des AOD dirigée par des pharmaciens et évaluer l'adhésion des patients à la pharmacothérapie, le respect de la fréquence des analyses sanguines recommandées dans les lignes directrices ainsi que les effets indésirables et ceux qui ne le sont pas. MÉTHODES: Cet examen rétrospectif des dossiers impliquait des patients ayant effectué leur première visite à la clinique AOD entre le 10 octobre 2017 et le 31 mai 2018. Les patients étaient suivis jusqu'au 30 novembre 2018. Les données analysées provenaient de dossiers d'hospitalisation électroniques et du réseau des pharmacies provinciales. Des statistiques descriptives ont servi à analyser les données : les variables catégorielles ont été présentées sous forme de fréquences et de pourcentages; les variables continues ont été analysées et présentées sous forme de moyennes avec les écarts-types et, le cas échéant, sous forme de moyennes avec les écarts interquartiles. RÉSULTATS: Quarante-sept patients, ayant effectué 74 visites en clinique, ont participé à l'étude. Vingt-huit patients (60 %) se conformaient à leur thérapie AOD. Les analyses sanguines de tous les patients ont été effectuées avant chaque rendez-vous en clinique. Le temps moyen entre le premier et le deuxième ensemble de tests sanguins était de 6,2 mois (écart-type standard [ET] 1,4), et de 5,1 mois (ET 1) entre le deuxième et le troisième. Aucun épisode de TEV ou d'hémorragie importante n'a eu lieu. Il y a eu un accident cérébrovasculaire (3,2 événements par 100 années-personnes; intervalle de confiance [IC] à 95 % 0,2­15,7) et 5 épisodes de saignements non majeurs et cliniquement pertinents (12,8 événements par 100 années-personnes, IC 95 % 4,1­30,1). Les pharmaciens ont décelé 51 problèmes lors des rendez-vous en clinique; parmi ceux-ci, 48 étaient liés aux médicaments. Il a fallu faire appel au médecin du service des thromboses pour résoudre 8 (16 %) problèmes. Une brève discussion entre ce médecin et le pharmacien a été nécessaire pour résoudre 30 (59 %) problèmes et 13 (25 %) ont été réglés uniquement par le pharmacien. CONCLUSIONS: Cette étude décrivait la mise en place et les résultats d'une nouvelle clinique AOD dirigée par les pharmaciens. Les patients de la clinique ont subi une analyse sanguine aux intervalles recommandés et ont reçu des conseils sur l'adhésion et les effets indésirables; les patients ont donc bénéficié d'un suivi conforme aux lignes directrices.

The experiences of family caregivers living with breast cancer patients in low-and middle-income countries: a systematic review.

INTRODUCTION: Caregivers of women with breast cancer in low-and-middle-income countries experience significant physical and economic burdens. The review aimed to map the evidence of studies that had reported on the experiences of family caregivers of women diagnosed with breast cancer. METHODS: A systematic literature search was conducted in CINAHL, PubMed, PsycINFO, Scopus, and Web of Science databases using a combination of key search terms and medical subject heading terms such as "family caregiver," "breast cancer," "home care," "low-and-middle-income countries," "experience," "effect," and "coping mechanism." A total of 1781 articles were retrieved and screened. Nineteen studies addressing caregiving experiences were included in the final review based on the inclusion and exclusion criteria. RESULTS: The systematic review yielded 19 studies that focused on caregivers' motivation, needs of caregivers, intervention for caregivers, and consequences of caregiving. The most significant correlates of the quality of life among caregivers were disease severity, functional status of patients, and family income. The challenges encountered by caregivers were mostly psychosocial. CONCLUSIONS: Caregivers play a crucial role in the management of women with breast cancer. However, they are faced with increasing challenges in their caregiving roles. Understanding the nature and extent of the burden experienced by family caregivers in developing countries will facilitate the development of appropriate interventions that can help improve caregivers' quality of life. Gaps in recent studies were identified, and suggestions for future research were also addressed in this review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118391.

Ambulatory blood pressure monitoring and management of hypertension at a cardiac clinic in Kumasi Metropolis, Ghana.

Ambulatory blood pressure monitoring (ABPM) is considered a good intervention strategy to avoid misdiagnosis of hypertension and allow for targeted treatment of patients with hypertension. This study sought to assess the contribution of ABPM to blood pressure (BP) control and antihypertensive therapy at a cardiac clinic in Ghana. Medical records of 97 patients, aged 18-85 years (mean 55), were reviewed. Among patients with clinic BP (CBP) and ambulatory BP recorded on the same day, we assessed for the different hypertension phenotypes, CBP control 6 months following ABPM, and changes to antihypertensive therapy after review of the ABPM records in patients with controlled and uncontrolled ambulatory BP. From the clinic and ambulatory BP records measured at baseline, the proportion of patients with white-coat uncontrolled hypertension (WUCH) was 19.5% (17/87) and those with masked uncontrolled hypertension (MUCH) was 16.1% (n = 14). A significant reduction in average systolic CBP in the overall cohort (-6.2 mm Hg, P < .01) and in the uncontrolled subgroup (-8.8 mm Hg, P < .001) at follow-up was observed. After review of the ABPM records, 51.7% of the patients on treatment had changes made in their antihypertensive therapy. Antihypertensive therapy was deintensified or left unchanged in majority of the patients with WUCH and sustained controlled hypertension. In patients with MUCH and true uncontrolled hypertension (TUCH), therapy was intensified. In conclusion, ABPM improved clinical decision-making for antihypertensive therapy and BP control. ABPM should therefore be used more often in hypertension and cardiac clinics in low/middle-income countries for optimal care.

Coronary intervention door-to-balloon time and outcomes in ST-elevation myocardial infarction: a meta-analysis.

OBJECTIVE: This study aims to determine the relationship between door-to-balloon delay in primary percutaneous coronary intervention and ST-elevation myocardial infarction (MI) outcomes and examine for potential effect modifiers. METHODS: We conducted a systematic review and meta-analysis of prospective observational studies that have investigated the relationship of door-to-balloon delay and clinical outcomes. The main outcomes include mortality and heart failure. RESULTS: 32 studies involving 299 320 patients contained adequate data for quantitative reporting. Patients with ST-elevation MI who experienced longer (>90 min) door-to-balloon delay had a higher risk of short-term mortality (pooled OR 1.52, 95% CI 1.40 to 1.65) and medium-term to long-term mortality (pooled OR 1.53, 95% CI 1.13 to 2.06). A non-linear time-risk relation was observed (P=0.004 for non-linearity). The association between longer door-to-balloon delay and short-term mortality differed between those presented early and late after symptom onset (Cochran's Q 3.88, P value 0.049) with a stronger relationship among those with shorter prehospital delays. CONCLUSION: Longer door-to-balloon delay in primary percutaneous coronary intervention for ST-elevation MI is related to higher risk of adverse outcomes. Prehospital delays modified this effect. The non-linearity of the time-risk relation might explain the lack of population effect despite an improved door-to-balloon time in the USA. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42015026069).

Pharmacological treatments for heart failure with preserved ejection fraction-a systematic review and indirect comparison.

Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), ß-adrenoceptor blockers (ß-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017. The study outcomes were mortality, hospitalization, changes in indexes of cardiac structure and function, biomarkers, and indexes of functional capacity-quality of life (QoL) assessment and 6-min walk distance test (6-MWD). The random-effects models were used to estimate pooled relative risks (RRs) for the binary outcomes and standardized mean differences for continuous outcomes, with 95% CI. A network meta-analysis using a random-effects model was employed to estimate the comparative efficacy of treatments. We included data from 15 RCTs comprising 5930 patients. There was no significant effect seen with all treatments compared with placebo and comparative efficacy of any two treatments on all outcomes assessed. However, mineralocorticoid antagonist spironolactone demonstrated a trend towards reducing mortality compared with placebo (RR 0.92; 95% CI 0.79-1.08), sildenafil (0.14; 0.01-2.78), perindopril (0.87; 0.59-1.28), and eplerenone (0.91; 0.25-3.33). Similar trends in treatment effect were observed with spironolactone on surrogate outcomes while eplerenone demonstrated a trend of superior effect in reduction of hospitalizations compared with all other drug treatment. No drug treatment demonstrated statistically significant improvement in clinical and surrogate outcomes in HFpEF diagnosed according to the ESC 2016 guideline. Spironolactone and eplerenone showed clinically relevant reduction in mortality and hospitalization respectively compared with other drug treatments. Further trials with MRAs are warranted to confirm treatment effects in HFpEF.

Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis.

BACKGROUND: Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF. METHODS AND RESULTS: This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use. CONCLUSIONS: Among Africans with HF, statin treatment was associated with significant reduction in mortality.

Clinical characteristics and prognosis of patients admitted for heart failure: A 5-year retrospective study of African patients.

BACKGROUND: Mortality associated with heart failure (HF) remains high. There are limited clinical data on mortality among HF patients from African populations. We examined the clinical characteristics, long-term outcomes, and prognostic factors of African HF patients with preserved, mid-range or reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We conducted a retrospective longitudinal cohort study of individuals aged ≥18years discharged from first HF admission between January 1, 2009 and December 31, 2013 from the Cardiac Clinic, Directorate of Medicine of the Komfo Anokye Teaching Hospital, Ghana. A total of 1488 patients diagnosed of HF were included in the analysis. Of these, 345 patients (23.2%) had reduced LVEF (LVEF<40%) [HFrEF], 265(17.8%) with mid-range LVEF (40%≥LVEF<50%) [HFmEF] and 878 (59.0%) had preserved LVEF (LVEF≥50%) [HFpEF]. Kaplan-Meier curves and log-rank test demonstrated better prognosis for HFpEF compared to HFrEF and HFmEF patients. An adjusted Cox analysis showed a significantly lower risk of mortality for HFpEF (hazard ratio (HR); 0.74; 95% confidence interval (CI) 0.57-0.94) p=0.015). Multivariate analyses showed that age, higher New York Heart Association (NYHA) functional class, lower LVEF, chronic kidney disease, atrial fibrillation, anemia, diabetes mellitus and absence of statin and aldosterone antagonist treatment were independent predictors of mortality in HF. Although, prognostic factors varied across the three groups, age was a common predictor of mortality in HFpEF and HFmEF. CONCLUSIONS: This study identified the clinical characteristics, long-term mortality and prognostic factors of African HF patients with reduced, mid-range and preserved ejection fractions in a clinical setting.

Review of novel therapeutic targets for improving heart failure treatment based on experimental and clinical studies.

Heart failure (HF) is a major public health priority due to its epidemiological transition and the world's aging population. HF is typified by continuous loss of contractile function with reduced, normal, or preserved ejection fraction, elevated vascular resistance, fluid and autonomic imbalance, and ventricular dilatation. Despite considerable advances in the treatment of HF over the past few decades, mortality remains substantial. Pharmacological treatments including ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists have been proven to prolong the survival of patients with HF. However, there are still instances where patients remain symptomatic, despite optimal use of existing therapeutic agents. This understanding that patients with chronic HF progress into advanced stages despite receiving optimal treatment has increased the quest for alternatives, exploring the roles of additional pathways that contribute to the development and progression of HF. Several pharmacological targets associated with pathogenesis of HF have been identified and novel therapies have emerged. In this work, we review recent evidence from proposed mechanisms to the outcomes of experimental and clinical studies of the novel pharmacological agents that have emerged for the treatment of HF.

Lipophilic Statin Versus Rosuvastatin (Hydrophilic) Treatment for Heart Failure: a Meta-Analysis and Adjusted Indirect Comparison of Randomised Trials.

OBJECTIVES: This study aims to compare lipophilic and hydrophilic statin therapy on clinical outcomes of heart failure (HF) using a systematic review and an adjusted indirect comparison meta-analysis. Outcomes were all-cause mortality, cardiovascular mortality, cardiovascular hospitalization and hospitalization for worsening HF. METHODS: We conducted a search of PubMed, EMBASE and Cochrane databases until 31st December 2014 for randomized control trials (RCTs) in HF evaluating statins versus placebo. Identified RCTs and their respective abstracted information were grouped according to statin type evaluated and analyzed separately. Outcomes were initially pooled with the Peto's one-step method, producing odd ratios (OR) and 95 % confidence intervals (CI) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons of lipophilic versus hydrophilic statin for each outcome. RESULTS: Thirteen studies involving 10,966 patients were identified and analyzed. Lipophilic statins were superior to hydrophilic rosuvastatin regarding all-cause mortality (OR 0 · 50; 95 % CI, 0 · 11-0 · 89; p = 0 · 01), cardiovascular mortality (OR 0 · 61; 0 · 25-0 · 97; p = 0 · 009), and hospitalization for worsening HF (OR 0 · 52; 0 · 21-0 · 83; p = 0 · 0005). However, both statins were comparable with regards to cardiovascular hospitalization [OR 0 · 80 (0 · 31, 1 · 28); p = 0 · 36]. CONCLUSIONS: Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.

Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.

INTRODUCTION: Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. AIMS: The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. METHOD: We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. RESULTS: Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P < 0.001), BNP (SMD, -1.60; 95% CI, -2.56 to -0.65; P < 0.001), hsCRP (SMD, -1.13; 95% CI, -1.54 to -0.72; P < 0.001), and IL-6 (SMD, -3.75; 95% CI, -4.77 to -0.72; P < 0.001) in HF. CONCLUSIONS: Lipophilic statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF.

Statins in heart failure: do we need another trial?

Statins lower serum cholesterol and are employed for primary and secondary prevention of cardiovascular events. Clinical evidence from observational studies, retrospective data, and post hoc analyses of data from large statin trials in various cardiovascular conditions, as well as small scale randomized trials, suggest survival and other outcome benefits for heart failure. Two recent large randomized controlled trials, however, appear to suggest statins do not have beneficial effects in heart failure. In addition to lowering cholesterol, statins are believed to have many pleotropic effects which could possibly influence the pathophysiology of heart failure. Following the two large trials, evidence from recent studies appears to support the use of statins in heart failure. This review discusses the role of statins in the pathophysiology of heart failure, current evidence for statin use in heart failure, and suggests directions for future research.

Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis.

BACKGROUND: Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF. METHODS/DESIGN: We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are:1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation.3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis.We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include:1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF.2. RCTs that employed the intention-to-treat (ITT) principle in data analysis.3. Symptomatic HF patients of all aetiologies and on standard treatment.4. Statin of any dose as intervention.5. Placebo or no statin arm as control.The exclusion criteria include:1. RCTs involving cerivastatin in HF patients.2. RCTs with less than 4 weeks of follow-up. DISCUSSION: We will perform an adjusted indirect comparison meta-analysis of lipophilic versus hydrophilic statins in patients with HF using placebo or no statin arm as common comparator.