Ross T. Tsuyuki

Comparison of Candesartan, Enalapril, and Their Combination in Congestive Heart Failure Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study: The RESOLVD Pilot Study Investigators

BACKGROUND We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF). METHODS AND RESULTS Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (0.025+/-0.004) than with candesartan alone (0.015+/-0.004) or enalapril alone(0.015+/-0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8+/-4 mL; ESV 1+/-4 mL; P<0.01) than with candesartan alone (EDV 27+/-4 mL; ESV 18+/-3 mL) or enalapril alone (EDV 23+/-7 mL; ESV 14+/-6 mL). Blood pressure decreased with combination therapy (6+/-1/4+/-1 mm Hg) compared with candesartan or enalapril alone (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2+/-5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7+/-7.8 pg/mL) or enalapril (-0.8+/-11. 3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8+/-2.7 pmol/L; P<0.01) compared with candesartan (4. 4+/-3.8 pmol/L) and enalapril alone (4.0+/-5.0 pmol/L). CONCLUSIONS Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.

A meta-analysis of the association between adherence to drug therapy and mortality

Abstract Objective To evaluate the relation between adherence to drug therapy, including placebo, and mortality. Design Meta-analysis of observational studies. Data sources Electronic databases, contact with investigators, and textbooks and reviews on adherence. Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality. Results Data were available from 21 studies (46 847 participants), including eight studies with placebo arms (19 633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11). Conclusion Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the “healthy adherer” effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.

Validity and reliability of the Edmonton Frail Scale

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Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: Diagnosis and management

Heart failure remains a common diagnosis, especially in older individuals. It continues to be associated with significant morbidity and mortality, but major advances in both diagnosis and management have occurred and will continue to improve symptoms and other outcomes in patients. The Canadian Cardiovascular Society published its first consensus conference recommendations on the diagnosis and management of heart failure in 1994, followed by two brief updates, and reconvened this consensus conference to provide a comprehensive review of current knowledge and management strategies. New clinical trial evidence and meta-analyses were critically reviewed by a multidisciplinary primary panel who developed both recommendations and practical tips, which were reviewed by a secondary panel. The resulting document is intended to provide practical advice for specialists, family physicians, nurses, pharmacists and others who are involved in the care of heart failure patients. Management of heart failure begins with an accurate diagnosis, and requires rational combination drug therapy, individualization of care for each patient (based on their symptoms, clinical presentation and disease severity), appropriate mechanical interventions including revascularization and devices, collaborative efforts among health care professionals, and education and cooperation of the patient and their immediate caregivers. The goal is to translate best evidence-based therapies into clinical practice with a measureable impact on the health of heart failure patients in Canada.

Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.

BACKGROUND Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease. METHODS We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model. FINDINGS Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98). INTERPRETATION Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder. FUNDING None.

Pharmacist Care of Patients With Heart Failure A Systematic Review of Randomized Trials

BACKGROUND While the role of multidisciplinary teams in the treatment of patients with heart failure (HF) is well established, there is less evidence to characterize the role of individual team members. To clarify the role of pharmacists in the care of patients with HF, we performed a systematic review evaluating the effect of pharmacist care on patient outcomes in HF. METHODS We searched PubMed, MEDLINE, EMBASE, International Pharmaceutical Abstracts, Web of Science, Scopus, Dissertation Abstracts, CINAHL, Pascal, and Cochrane Central Register of Controlled Trials for controlled studies from database inception to August 2007. We included randomized controlled trials that evaluated the impact of pharmacist care activities on patients with HF (in both inpatient and outpatient settings). Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model for rates of all-cause hospitalization, HF hospitalization, and mortality. RESULTS A total of 12 randomized controlled trials (2060 patients) were identified. Extent of pharmacist involvement varied among studies, and each study intervention was categorized as pharmacist-directed care or pharmacist collaborative care using a priori definitions and feedback from primary study authors. Pharmacist care was associated with significant reductions in the rate of all-cause hospitalizations (11 studies [2026 patients]) (OR, 0.71; 95% CI, 0.54-0.94) and HF hospitalizations (11 studies [1977 patients]) (OR, 0.69; 95% CI, 0.51-0.94),and a nonsignificant reduction in mortality (12 studies [2060 patients])(OR, 0.84; 95% CI, 0.61-1.15). Pharmacist collaborative care led to greater reductions in the rate of HF hospitalizations (OR, 0.42; 95%CI, 0.24-0.74) than pharmacist-directed care (OR, 0.89; 95% CI, 0.68-1.17). CONCLUSIONS Pharmacist care in the treatment of patients with HF greatly reduces the risk of all-cause and HF hospitalizations. Since hospitalizations associated with HF are a major public health problem, the incorporation of pharmacists into HF care teams should be strongly considered.

Dose–response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study

Background: Over the past 30 years, the relation between use of sulfonylureas to treat type 2 diabetes and the risk of cardiovascular events has been vigorously debated. The purpose of this study was to determine if the risk of death changes with level of exposure to sulfonylurea drugs. Methods: This was a retrospective, inception cohort study using administrative data from Saskatchewan Health (1991– 1999). The 5795 subjects, identified by their first-ever dispensation for an oral antidiabetic agent, were grouped according to their use of such agents during follow-up. Potential subjects using insulin or combination therapy were excluded. Exposure level was defined by daily dose and degree of adherence. Separate multivariate Cox proportional-hazard models were constructed for each monotherapy group and used to calculate the risk of death associated with higher versus lower exposure category. Disease severity indicators were identified among the administrative data and entered as covariates in each model. The main outcomes were all-cause mortality and death from an acute ischemic event. Results: The mean age of the cohort members was 66.3 (standard deviation [SD] 13.4) years; 43.4% were female; and their mean duration of follow-up was 4.6 (SD 2.1) years. First-generation sulfonylureas were used exclusively by 120 subjects; glyburide, by 4138; and metformin, by 1537. A greater risk of death was associated with higher daily doses of the first-generation sulfonylureas (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.0–4.7) and glyburide (HR 1.3, 95% CI 1.2–1.4), but not metformin (HR 0.8, 95% CI 0.7–1.1). Similar associations were observed for death caused by an acute ischemic event. Interpretation: Higher exposure to sulfonylureas was associated with increased mortality among patients newly treated for type 2 diabetes. The same relation was not observed with metformin. This implies that the manner in which blood glucose concentration is lowered may be as important as achieving recommended glucose targets.

Effect of fish oil on arrhythmias and mortality: systematic review.

Objective To synthesise the literature on the effects of fish oil—docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—on mortality and arrhythmias and to explore dose response and formulation effects. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised controlled trials of fish oil as dietary supplements in humans. Data extraction The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. Data synthesis 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. Conclusions Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations for DHA and EPA remain unclear.

Blood-pressure reduction and cardiovascular risk in HOPE study

In the Heart Outcomes Prevention Evaluation (HOPE) study, use of the angiotensin-converting-enzyme inhibitor ramipril was associated with a 22% relative risk reduction in cardiovascular death, myocardial infarction, or stroke, despite only a modest reduction in blood pressure (23.3 mm Hg systolic). To test the hypothesis that the benefits seen were not due to reduced blood pressure alone, we calculated blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. We found that the benefits seen in HOPE were around three times greater than predicted from these calculations. In this well treated and largely normotensive population with coronary disease, but good left-ventricular function, the benefits from ramipril were additive to other proven therapies in normotensive patients and in those with higher baseline blood pressure.

A Randomized Trial of the Effect of Community Pharmacist and Nurse Care on Improving Blood Pressure Management in Patients With Diabetes Mellitus: Study of Cardiovascular Risk Intervention by Pharmacists–Hypertension (SCRIP-HTN)

BACKGROUND Blood pressure (BP) control in patients with diabetes mellitus is difficult to achieve and current patterns are suboptimal. Given increasing problems with access to primary care physicians, community pharmacists and nurses are well positioned to identify and observe these patients. This study aimed to determine the efficacy of a community-based multidisciplinary intervention on BP control in patients with diabetes mellitus. METHODS We performed a randomized controlled trial in 14 community pharmacies in Edmonton, Alberta, Canada, of patients with diabetes who had BPs higher than 130/80 mm Hg on 2 consecutive visits 2 weeks apart. Care from a pharmacist and nurse team included a wallet card with recorded BP measures, cardiovascular risk reduction education and counseling, a hypertension education pamphlet, referral to the patients primary care physician for further assessment or management, a 1-page local opinion leader-endorsed evidence summary sent to the physician reinforcing the guideline recommendations for the treatment of hypertension and diabetes, and 4 follow-up visits throughout 6 months. Control-arm patients received a BP wallet card, a pamphlet on diabetes, general diabetes advice, and usual care by their physician. The primary outcome measure was the difference in change in systolic BP between the 2 groups at 6 months. RESULTS A total of 227 eligible patients were randomized to intervention and control arms between May 5, 2005, and September 1, 2006. The mean (SD) patient age was 64.9 (12.1) years, 59.9% were male, and the mean (SD) baseline systolic/diastolic BP was 141.2 (13.9)/77.3 (8.9) mm Hg at baseline. The intervention group had an adjusted mean (SE) greater reduction in systolic BP at 6 months of 5.6 (2.1) mm Hg compared with controls (P = .008). In the subgroup of patients with a systolic BP greater than 160 mm Hg at baseline, BP was reduced by an adjusted mean (SE) of 24.1 (1.9) mm Hg more in intervention patients than in controls (P < .001). CONCLUSION Even in patients who have diabetes and hypertension that are relatively well controlled, a pharmacist and nurse team-based intervention resulted in a clinically important improvement in BP. Trial Registration clinicaltrials.gov Identifier: NCT00374270.