Carol E. Koro

Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse. This was a retrospective cohort study using electronic health care records. Participants were anemic hemodialysis patients treated during February 2012 and were followed for 15 months. Patients’ ESA response (responders) or lack of response (chronic and acute hyporesponders) based on longitudinal patterns of ESA dose and hemoglobin level was assessed. Persistence of hyporesponse, longitudinal iron measures, transfusion rates, and mortality rates were analyzed. Frequency of blood transfusions (monthly) and death rates (quarterly) were calculated. Log normalized serum ferritin concentration was analyzed. Of 97,677 eligible patients, 6632 had acute hyporesponsiveness (ESA responsiveness restituted in ≤ 4 months) and 3086 had chronic hyporesponsiveness (lack of ESA response for > 4 months). Over months 1–4 among chronic hyporesponders, mean serum ferritin (722–785 ng/mL) and transferrin saturation (TSAT; 26.76 %-27.08 %) were constant, while acute hyporesponsive patients experienced increased ferritin (654-760 ng/mL) and TSAT (25.71–30.88 %) levels. Compared to ESA responders (0.19–0.30 %), chronic hyporesponders were transfused 7-times (1.20–2.17 %) more frequently over follow-up. Quarterly mortality was greatest in chronic ESA hyporesponders (2.98–5.48 %), followed by acute ESA hyporesponders (2.17–3.30 %) and ESA responders (1.43–2.49 %). With consistence over the study, chronic hyporesponders died more frequently than patients in the other study cohorts. Findings indicate that 4 months of continuous ESA hyporesponsiveness can be used to differentiate acute from chronic hyporesponsiveness. This definition of chronic hyporesponsiveness is supported by outcome data showing higher mortality and transfusion rates in chronic hyporesponders compared to acute hyporesponders.

Purpose To determine the likelihood of myocardial infarction (MI) in type 2 diabetic patients exposed to rosiglitazone and pioglitazone, separately, compared to other antidiabetic therapies. Methods A case–control analysis nested within the cohort of type 2 diabetic subjects from the Integrated Healthcare Information Services (IHCIS) claims database. Incident cases of MI were matched to three controls each on age (±5 years), gender, and year of first diabetes diagnosis. Subjects were classified according to their antidiabetic drug exposure in the 3, < 6, 6–12, and > 12 months prior to the index date. The adjusted odds ratios of MI were calculated for subjects exposed to rosiglitazone and pioglitazone, separately, compared to other antidiabetic agents. Risk factors adjusted for are age, ACE inhibitors, β‐blockers, diuretics, nitrates, diagnosis of hyperlipidemia, and hypertension and coronary artery disease (CAD). Results A total of 891 901 diabetic subjects (9870 cases and 29 610 control) identified from 1999 to 2006 were included in the analysis. The mean age was 63 years for the cases and controls. Compared to those treated with other antidiabetic therapies, the adjusted odds ratio of MI was 1.03 [95%CI: 0.93–1.12] for rosiglitazone and 0.92 [95%CI: 0.83–1.01] for pioglitazone in the 3 months prior to the index date. Conclusions The results suggest that the risk of MI in subjects exposed to rosiglitazone or pioglitazone for ≤ 12 months is not different from those exposed to other antidiabetic agents but exposure for > 12 months is associated with 15 and 13% increased risk of MI, respectively. Copyright © 2008 John Wiley & Sons, Ltd.

Purpose To evaluate whether the risk of coronary heart disease (CHD) differs among adult diabetic patients treated with thiazolidinediones (TZDs) and similar patients treated with combined oral metformin and sulfonylurea (M + S) therapy. Methods We conducted a retrospective cohort study involving 25 140 diabetic patients aged 18 and older who had at least one pharmacy claim for a TZD or combined M + S therapy between 1 January 1999 and 30 June 2002. We used propensity score matching to adjust for observable differences between initiators of combined M + S therapy and TZD initiators. The data were analyzed in two ways: first based on the original matched groups, ‘as balanced’, without accounting for switching to another medication during follow‐up, and second based on actual antidiabetic drug use during follow‐up, ‘as treated’. Cox proportional hazards regression and multivariable Poisson regression were performed to compare the risk of CHD events. Results In the ‘as balanced’ analysis, the risk for CHD among TZD users relative to combination drug users was close to the null value (adjusted hazard ratio: 1.02, 95% confidence intervals (CI): 0.87–1.20). In the ‘as treated’ analysis, the risk of CHD was similar for periods of current use of TZDs compared to periods of non‐use (incidence rate ratio: 1.10, 95%CI: 0.96–1.25). Conclusions These results do not suggest a cardioprotective or deleterious effects of TZDs compared with combined M + S oral therapy on the short‐term CHD event risk in persons with type 2 diabetes after accounting for the greater baseline CHD risk in TZD initiators. Copyright © 2007 John Wiley & Sons, Ltd.

Purpose This study assesses the effect of the type of antidiabetic treatment on the risk of developing congestive heart failure (CHF) in type 2 diabetes. Methods The study was derived from the U.K.-based General Practice Research Database (GPRD) comprised of 3.5 million subjects followed between 1987 and 2001. A total of 21 888 type 2 diabetic patients were identified. A 6:1 matched nested case-control design was employed. Conditional logistic regression was used to derive adjusted odds ratios (ORs) for the association of drug treatment with CHF controlling for diabetes duration and for diseases known to affect the risk of CHF. Antidiabetic drug exposure was defined as the receipt of at least one prescription for an antidiabetic medication within the 3 months prior to the date of CHF diagnosis. Results There were 1301 incident cases of CHF in the cohort, matched to 7788 controls. After risk factor adjustment, there was a 1.2-fold increase in the risk of CHF for sulphonylureas (SUs) (OR = 1.17; 95%CI = 1.00–1.37) and metformin monotherapies (OR = 1.22; 95%CI = 0.97–1.52), a 1.6-fold increase with combinations of metformin and SUs (OR = 1.62; 95%CI = 1.30–2.02), a 2.2-fold increase with oral tricombinations (OR = 2.16; 95%CI = 0.96–4.86) and a 1.5-fold increase for insulin compared to no exposure (OR = 1.52; 95%CI = 1.06–2.17). Compared to SUs, bicombinations of metformin and SUs showed a statistically significant 1.4-fold increase in the odds of CHF (OR = 1.38; 95%CI = 1.13–1.69). Conclusions All antidiabetic medications were associated with an increased likelihood of CHF compared to no antidiabetic exposure. The risk of CHF increased with the complexity of the antidiabetic regimen suggesting that it is the diabetes severity, which imparts risk and not necessarily the antidiabetic regimen itself. Copyright © 2005 John Wiley & Sons, Ltd.

Conclusions Among African-Americans, more women than men are eligible for treatment under the new ATP III guidelines. Eligibility in women is based primarily on diabetes and lipid levels rather than absolute Framingham risk, which seems to be underestimated in African-American women. As compensation for this underestimate, drug-optional (lower) targets should be applied to this population.