Scot H. Simpson

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.

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.

Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes

Aim  Metformin therapy reduces microvascular complications in Type 2 diabetes; questions remain, however, regarding its impact on macrovascular events. This study examined metformin use in relation to risk of cardiovascular‐related hospitalization and mortality.

Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study

Objective To determine if the use of sitagliptin in newly treated patients with type 2 diabetes is associated with any changes in clinical outcomes. Design Retrospective population based cohort study. Setting Large national commercially insured US claims and integrated laboratory database. Participants Inception cohort of new users of oral antidiabetic drugs between 2004 and 2009 followed until death, termination of medical insurance, or December 31 2010. Main outcome measure Composite endpoint of all cause hospital admission and all cause mortality, assessed with time varying Cox proportional hazards regression after adjustment for demographics, clinical and laboratory data, pharmacy claims data, healthcare use, and time varying propensity scores. Results The cohort included 72 738 new users of oral antidiabetic drugs (8032 (11%) used sitagliptin; 7293 (91%) were taking it in combination with other agents) followed for a total of 182 409 patient years. The mean age was 52 (SD 9) years, 54% (39 573) were men, 11% (8111) had ischemic heart disease, and 9% (6378) had diabetes related complications at the time their first antidiabetic drug was prescribed. 14 215 (20%) patients met the combined endpoint. Sitagliptin users showed similar rates of all cause hospital admission or mortality to patients not using sitagliptin (adjusted hazard ratio 0.98, 95% confidence interval 0.91 to 1.06), including patients with a history of ischemic heart disease (adjusted hazard ratio 1.10, 0.94 to 1.28) and those with estimated glomerular filtration rate below 60 mL/min (1.11, 0.88 to 1.41). Conclusions Sitagliptin use was not associated with an excess risk of all cause hospital admission or death compared with other glucose lowering agents among newly treated patients with type 2 diabetes. Most patients prescribed sitagliptin in this cohort were concordant with clinical practice guidelines, in that it was used as add-on treatment.

Insulin use and increased risk of mortality in type 2 diabetes: a cohort study

Aim: To compare population‐based rates of all‐cause and cardiovascular (CV) mortality in newly treated patients with type 2 diabetes according to levels of insulin exposure.

A Systematic Review of Patient Self-Reported Barriers of Adherence to Antihypertensive Medications Using the World Health Organization Multidimensional Adherence Model

J Clin Hypertens (Greenwich). 2012;14:877–886. ©2012 Wiley Periodicals, Inc.

Effect of Adding Pharmacists to Primary Care Teams on Blood Pressure Control in Patients With Type 2 Diabetes A randomized controlled trial

OBJECTIVE To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a randomized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton, Canada. Pharmacists performed medication assessments and limited history and physical examinations and provided guideline-concordant recommendations to optimize medication management. Follow-up contact was completed as necessary. Control patients received usual care. The primary outcome was a ≥10% decrease in systolic blood pressure at 1 year. RESULTS A total of 260 patients were enrolled, 57% were women, the mean age was 59 years, diabetes duration was 6 years, and blood pressure was 129/74 mmHg. Forty-eight of 131 (37%) intervention patients and 30 of 129 (23%) control patients achieved the primary outcome (odds ratio 1.9 [95% CI 1.1–3.3]; P = 0.02). Among 153 patients with inadequately controlled hypertension at baseline, intervention patients (n = 82) were significantly more likely than control patients (n = 71) to achieve the primary outcome (41 [50%] vs. 20 [28%]; 2.6 [1.3–5.0]; P = 0.007) and recommended blood pressure targets (44 [54%] vs. 21 [30%]; 2.8 [1.4–5.4]; P = 0.003). The 10-year risk of cardiovascular disease, based on changes to the UK Prospective Diabetes Study Risk Engine, were predicted to decrease by 3% for intervention patients and 1% for control patients (P = 0.005). CONCLUSIONS Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams, which suggests that pharmacists can make important contributions to the primary care of these patients.

Recurrent Community-acquired Pneumonia in Patients Starting Acid-suppressing Drugs

BACKGROUND Several studies suggest that proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H2s) increase risk of community-acquired pneumonia. To test this hypothesis, we examined a prospective population-based cohort predisposed to pneumonia: elderly patients (> or =65 years) who had survived hospitalization for pneumonia. METHODS This study featured a nested case-control design where cases were patients hospitalized for recurrent pneumonia (> or =30 days after initial episode) and controls were age, sex, and incidence-density sampling matched but never had recurrent pneumonia. PPI/H2 exposure was classified as never, past, or current use before recurrent pneumonia. The association between PPI/H2s and pneumonia was assessed using multivariable conditional logistic regression. RESULTS During 5.4 years of follow-up, 248 recurrent pneumonia cases were matched with 2476 controls. Overall, 71 of 608 (12%) current PPI/H2 users had recurrent pneumonia, compared with 130 of 1487 (8%) nonusers (adjusted odds ratio [aOR] 1.5; 95% confidence interval [CI], 1.1-2.1). Stratifying the 608 current users according to timing of PPI/H2 initiation revealed incident current-users (initiated PPI/H2 after initial pneumonia hospitalization, n=303) bore the entire increased risk of recurrent community-acquired pneumonia (15% vs 8% among nonusers, aOR 2.1; 95% CI, 1.4-3.0). The 305 prevalent current-users (PPI/H2 exposure before and after initial community-acquired pneumonia hospitalization) were equally likely to develop recurrent pneumonia as nonusers (aOR 0.99; 95% CI, 0.63-1.57). CONCLUSION Acid-suppressing drug use substantially increased the likelihood of recurrent pneumonia in high-risk elderly patients. The association was confined to patients initiating PPI/H2s after hospital discharge. Our findings should be considered when deciding to prescribe these drugs in patients with a recent history of pneumonia.

Mortality risk among sulfonylureas: a systematic review and network meta-analysis

BACKGROUND Sulfonylureas are common second-line options for management of type 2 diabetes; however, they are associated with a higher risk of cardiovascular events compared with other antidiabetic drugs. Since tissue selectivity and risk of hypoglycaemia differ among sulfonylureas, we aimed to assess whether mortality and the risk of cardiovascular events also varies. METHODS We searched Medline and Embase from inception to June 11, 2014, to identify controlled studies reporting the risk of all-cause mortality, cardiovascular-related mortality, or myocardial infarction for at least two sulfonylureas. We examined differences in cardiovascular event risk among sulfonylureas with random effects models for direct pairwise comparisons and network meta-analyses to incorporate direct and indirect data. FINDINGS 14 970 (9%) of 167 327 patients in 18 studies died: 841 (4%) of 19 334 gliclazide users, 5482 (11%) of 49 389 glimepiride users, 2106 (15%) of 14 464 glipizide users, 5296 (7%) of 77 169 glibenclamide users, 1066 (17%) of 6187 tolbutamide users, and 179 (23%) of 784 chlorpropamide users. Inconsistency was low for the network meta-analysis of all-cause mortality, and the relative risk of death compared with glibenclamide was 0·65 (95% credible interval 0·53-0·79) for gliclazide, 0·83 (0·68-1·00) for glimepiride, 0·98 (0·80-1·19) for glipizide, 1·13 (0·90-1·42) for tolbutamide, and 1·34 (0·98-1·86) for chlorpropamide. Similar associations were noted for cardiovascular-related mortality: the relative risk compared with glibenclamide was 0·60 (95% credible interval 0·45-0·84) for gliclazide, 0·79 (0·57-1·11) for glimepiride, 1·01 (0·72-1·43) for glipizide, 1·11 (0·79-1·55) for tolbutamide, and 1·45 (0·88-2·44) for chlorpropamide. INTERPRETATION Gliclazide and glimepiride were associated with a lower risk of all-cause and cardiovascular-related mortality compared with glibenclamide. Clinicians should consider possible differences in risk of mortality when selecting a sulfonylurea. FUNDING None.