A.S. Chitnis

Effect of certain angiotensin-converting enzyme inhibitors on mortality in heart failure: a multiple-propensity analysis.

BACKGROUND Heart failure is a major and growing public health problem in United States. There is a substantial evidence about efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in heart failure (HF); however, there is no conclusive evidence on the relative effectiveness of individual ACEIs. OBJECTIVE To evaluate the effect of individual ACEIs on mortality using multiple-propensity score analysis in a large real-world population. METHODS The study was a retrospective analysis of a national cohort of patients with HF identified from the Department of Veterans Affairs. A multiple-propensity score analysis was used to balance 47 baseline patient characteristics between different nontissue ACEIs. The effect of different ACEIs on time to death was assessed using a propensity score-weighted, multivariable Cox proportional hazard model. RESULTS The study included 139,994 patients with 69.50% (97,293) on lisinopril, 21.79% (30,503) on fosinopril, 8.41% (11,775) on captopril, and 0.30% (423) on enalapril. Propensity scores balanced nearly all differences between different ACEI groups. Fosinopril (hazard ratio [HR]=0.739, 95% confidence interval [CI]: 0.686-0.797) and lisinopril (HR=0.818, 95% CI: 0.766-0.874) were significantly associated with reduced mortality as compared with captopril. Similar mortality was observed with enalapril (HR=0.944, 95% CI: 0.675-1.320) as compared with captopril. CONCLUSIONS In patients with HF, fosinopril and lisinopril were associated with lower mortality as compared with captopril. However, the results of this observational study should be interpreted with caution, and need to be replicated and confirmed in studies for which HF severity data are available.

Development and validation of RP-HPLC method for estimation of eplerenone in spiked human plasma

A rapid and simple high performance liquid chromatography (HPLC) method with a UV detection (241 nm) was developed and validated for estimation of eplerenone from spiked human plasma. The analyte and the internal standard (valdecoxib) were extracted with a mixture of dichloromethane and diethyl ether. The chromatographic separation was performed on a HiQSil C-18HS column (250 mm×4.6 mm, 5 μm) with a mobile phase consisting of acetonitrile:water (50:50, v/v) at flow rate of 1 mL/min. The calibration curve was linear in the range 100–3200 ng/mL and the heteroscedasticity was minimized by using weighted least squares regression with weighting factor 1/X.

Comparative effectiveness of different angiotensin-converting enzyme inhibitors on the risk of hospitalization in patients with heart failure

AIMS Existing randomized controlled trials do not address the comparative effectiveness of different angiotensin-converting enzyme inhibitors (ACEIs) on hospitalization due to heart failure (HF)-hospitalization in patients with HF. We sought to examine the effect of four ACEIs on HF-hospitalization in a large real-world HF population. METHODS The study was a retrospective analysis of a national cohort of patients with HF identified from the Department of Veterans Affairs (TX, USA). A multiple propensity score analysis was used to balance 47 baseline patient characteristics between the different ACEIs. The effect of different ACEIs on time to HF-hospitalization was assessed using the multiple propensity score-weighted multivariable Cox proportional hazard model. RESULTS The study included 139,994 patients with 69.50% (97,293) on lisinopril, 21.79% (30,503) on fosinopril, 8.41% (11,775) on captopril and 0.30% (423) on enalapril. Propensity scores balanced nearly all differences between different ACEIs groups. Enalapril (hazard ratio [HR]: 0.800; 95% CI: 0.492-1.297), fosinopril (HR: 0.971; 95% CI: 0.877-1.074), and lisinopril (HR: 1.005; 95% CI: 0.918-1.101) when compared with captopril were found to have similar effectiveness in reducing HF-hospitalizations. CONCLUSION In patients with HF, we found that the four ACEIs are equally effective in reducing HF-hospitalization in day-to-day practice.

Comparative effectiveness research: guidelines for good practices are just the beginning

The International Society for Pharmacoeconomics and Outcomes Research formed a task force to gather state-of-the-art recommendations on good research practices for comparative effectiveness research using retrospective databases. The report of the task force was published in three sections in the journal Value in Health in December 2009, and addressed issues of design, analysis, framing the research question, and reporting and interpreting the findings from nonrandomized studies of treatment effects. This article will briefly examine the structure, process and outcomes of that task force, comment on the potential impact of the report in the context of comparative effectiveness research, and offer a few observations on the future of this field.

Use of Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Risk of Dementia in Heart Failure

Objective: To test the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) on reducing the risk of dementia in patients with heart failure (HF). Methods: This retrospective, longitudinal study used a cohort of HF patients identified from a local Medicare advantage prescription drug plan. Multivariable time-dependent Cox model and marginal structural model using inverse-probability-oftreatment weighting were used to estimate the risk of developing dementia. Adjusted dementia rate ratios were estimated among current and former ACEI/ARB users, as compared with nonusers. Results: Using the time-dependent Cox model, the adjusted dementia rate ratios (95% confidence-interval) among current and former users were 0.90(0.70-1.16) and 0.89 (0.71-1.10), respectively. Use of marginal structural model resulted in similar effect estimates for current and former users as compared with the nonusers. Conclusion: This study found no difference in risk of dementia among the current and former users of ACEI/ARB as compared with the nonusers in an already at-risk HF population.

PCV9 COMPARATIVE EFFECTIVENESS OF INDIVIDUAL ANGIOTENSINCONVERTING ENZYME INHIBITORS IN PATIENTS WITH CHRONIC HEART FAILURE

plan in US covering 4 million lives. Outcomes measure was any occurrence of CV including ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. A multivariate logistic model was developed to evaluate adjusted CV-risk. Multicollinearity test and Hosemer-Lemeshow test were performed. RESULTS: Mean( / SD) age was 57( / 8) years in combo-group(N 53) and 57( / 11) years in mono-group(N 5670). In combo-group, mean( / SD) treatment-duration was 779( / 424) days for statin fi brate combination-therapy. In mono-group, mean( / SD) treatment-duration was 987( / 588) days for statin-monotherapy. Unadjusted CV-rates of combo-group versus mono-group were not signifi cantly different (odds ratio [OR] 1.39, P 0.2313). Although adjusting for age, gender, prior CV, CV related pharmacy-costs, total medical-costs, diabetes with complication, and Elixhauser-comorbidity, CV-rates of combo-group versus mono-group were not signifi cantly different (OR 1.186, P 0.5929). All covariates were signifi cantly associated with CV-rates. The model did not suffer from multicollinearity and the model goodness-of-fi t was satisfactory (P 0.5575). CONCLUSIONS: In a managed care population with type-II diabetes after adjusting for known baseline differences, CVrisks among subjects who used statin fi brate combination-therapy compared to those who used statin-monotherapy did not signifi cantly differ. This is different from what people expected for the combination-therapy, due to low power resulting from small sample size for combo-group. We hope this result will be useful in health policy to fi nd treatment strategies to reduce CV-risk in diabetics. Future research is in progress to address the causality behind this association.