Meenal Patwardhan

Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension

Context Are angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) more effective for treating essential hypertension? Contribution This systematic review of trials that directly compared ACE inhibitors and ARBs in adults with essential hypertension found good evidence that the agents had similar long-term effects on blood pressure. There were no consistent differential effects for mortality, cardiovascular events, progression to diabetes, left ventricular function, or kidney disease. Cough was more frequent with ACE inhibitors than ARBs. Implication Both ACE inhibitors and ARBs have similar effects on blood pressure and may not have differential effects on other clinical outcomes, although ACE inhibitors do cause cough more often than ARBs. The Editors More than 65 million U.S. adultsapproximately one thirdhave hypertension. In addition to being the leading attributable risk factor for death throughout the world (1), hypertension results in substantial illness due to its effect on several target organs, including the brain, eyes, heart, arteries, and kidneys. Despite the high rate of morbidity and mortality attributable to hypertension, control remains suboptimal (2). In addition to several effective nonpharmacologic interventions, many individuals require antihypertensive medication to lower blood pressure and often require several medications together (2). Among the most common of the many choices in antihypertensive therapy are those aimed at inhibiting the reninangiotensinaldosterone (renin) system. Currently, renin system inhibitors include angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Although clinicians regard ACE inhibitors and ARBs as effectively equivalent, it is not clear whether this is appropriate. For example, ACE inhibitors do not entirely block production of angiotensin II because of other, unaffected converting enzymes. Also, ACE inhibitors are associated with well-known adverse events not shared by ARBs, including cough (estimated incidence, 5% to 20%) and the possibly related phenomenon of angioedema (estimated incidence, 0.1% to 0.2%) (3). Although both ACE inhibitors and ARBs are highly effective in lowering blood pressure among patients with essential hypertension (4, 5), their comparative effectiveness and the relative advantages and disadvantages of ACE inhibitors versus ARBs are unknown. This review summarizes the evidence on the comparative long-term benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. The full technical report was commissioned by the Agency for Healthcare Research and Quality (6). Methods We developed and followed a standardized protocol for all steps of the review. Data Sources and Searches We searched MEDLINE (1966 to week 3 of May 2006) and the Cochrane Central Register of Controlled Trials (Issue 2, 2006) for studies published in English after 1988, using terms for drug interventions, hypertension, and study design. We also reviewed bibliographies submitted by pharmaceutical companies to the Scientific Resource Center for the Agency for Healthcare Research and Qualitys Effective Health Care Program, reference lists of relevant review articles, and citations identified by reviewers of the draft report. For the current review, we updated our MEDLINE search to August 2007 to identify new head-to-head trials that reported blood pressure outcomes and major cardiovascular events. Results from the newly identified studies (721) were consistent with the evidence described in the full technical report and are not presented here. Study Selection We included comparative clinical studies of any design (including randomized, controlled trials and nonrandomized, controlled trials; cohort studies; and casecontrol studies) that provided direct comparisons of ACE inhibitors versus ARBs at 12 weeks or more after the initial intervention. In addition to simple comparisons of a single ACE inhibitor versus a single ARB, we included studies with grouped comparisons (such as a specific ARB versus ACE inhibitors or unspecified ARBs versus unspecified ACE inhibitors) and comparisons in which the same drug was administered with an ACE inhibitor versus that drug with an ARB (for example, losartan and hydrochlorothiazide vs. enalapril and hydrochlorothiazide). We excluded studies with comparisons in which the drugs administered with an ACE inhibitor differed from those administered with an ARB (for example, enalapril and manidipine vs. irbesartan and hydrochlorothiazide). We included studies with treatment protocols that permitted the addition of other antihypertensive medications during the trial, provided that the co-intervention protocols were the same in the ACE inhibitor and ARB treatment groups. Outcomes we considered included blood pressure control, adherence, quality of life, several intermediate outcomes, and harms. We excluded studies with fewer than 20 total patients in the ACE inhibitor and ARB treatment groups and focused on studies of adults (18 years of age) with essential hypertension, as defined by the study authors. We also evaluated studies of ARBs versus other (nonACE inhibitor) comparators and ACE inhibitors versus other (non-ARB) comparators, which were to be considered in case too few direct head-to-head trials were identified for outcomes of interest. Appendix 1 contains the details of how we identified and reviewed indirect comparison studies. Data Extraction and Quality, Applicability, and Strength of Evidence Assessments One author extracted data from each study, which were confirmed by another author. Extracted information included study design; interventions; population characteristics; recruitment setting; inclusion and exclusion criteria; numbers of participants screened, eligible, enrolled, and lost to follow-up; and results for each outcome. We used predefined criteria adapted from those developed by the U.S. Preventive Services Task Force (22) and the Centre for Reviews and Dissemination in the United Kingdom (23) to assess the quality of individual studies as good, fair, or poor, and we noted important limitations on internal validity for studies rated as fair or poor. The applicability of individual studies was assessed by noting the most important potential limitations (up to 3) in a studys applicability from among the list described by Rothwell (24), as adapted by the Scientific Resource Center (Appendix 2). Quality and applicability assessments are detailed for individual studies in the evidence tables included in the full report (6). Finally, we assessed the strength of the body of evidence for each key question as high, moderate, low, or very low by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework (25). Data Synthesis and Analysis Given that many studies did not have the statistical power to determine equivalence for relevant outcomes, we considered pooling (without regard to the specific drug within the ACE inhibitor or ARB class) to overcome a type II error. In evaluating direct comparison studies for potential data synthesis, we primarily considered clinical homogeneity. In general, we considered groups of studies as suitable for quantitative synthesis when we identified at least 4 clinically and relatively similar studies that assessed the same outcome. We used additional and more detailed criteria to determine suitability for pooling of indirect comparisons, as such comparisons are tenuous (Appendix 1). We did not attempt to pool direct and indirect comparison studies in a single analysis, primarily because we did not identify a sufficient number of clinically similar indirect comparison studies to analyze. When we pooled studies, we used the random-effects model for the primary analysis and the fixed-effect model for sensitivity analysis. We stratified analyses by study design, separating randomized, controlled trials from observational studies. We performed all analyses by using Comprehensive Meta-analysis, version 2 (Biostat, Englewood, New Jersey). For count outcomes, we calculated summaries of the relative effect (odds ratios) and absolute effect (risk difference). We chose the Peto method for analyzing data on cough and withdrawals due to adverse events because event rates were low and treatment groups were not substantially imbalanced, conditions under which this method is the least biased and most powerful (26). This method also allows inclusion of studies with zero events in 1 group with no continuity correction. For data on rates of successful monotherapy, we used risk differences because event rates were high, which makes the assumption of a constant odds ratio unreasonable. Role of the Funding Source The Agency for Healthcare Research and Quality formulated the initial study questions and reviewed and commented on planned methods, data analysis, and the draft report. The funding source did not participate in the search of the literature, determination of study eligibility, or evaluation of individual studies. Results Of 1185 citations, 69 reports (61 distinct studies) directly compared ACE inhibitors with ARBs (Figure 1). Forty-seven studies were randomized, controlled trials; 1 was a nonrandomized, controlled trial; 9 were retrospective cohort studies; 2 were prospective cohort studies; 1 was a cross-sectional cohort study; and 1 was a casecontrol study. Table 1 shows the numbers of studies that compared different agents. Enalapril was the most frequently studied ACE inhibitor (24 studies), and losartan the most frequently studied ARB (19 studies). Most studies were relatively short-term; 19 followed patients for 12 weeks, and 21 followed patients between 12 weeks and 6 months. Most studies excluded patients with secondary causes of hypertension, as well as patients with recent acute events, such as myocardial infarction or stroke. Table 2 summarizes the number

Improving Health Care Efficiency and Quality Using Tablet Personal Computers to Collect Research-Quality, Patient-Reported Data

OBJECTIVE To determine whether e/Tablets (wireless tablet computers used in community oncology clinics to collect review of systems information at point of care) are feasible, acceptable, and valid for collecting research-quality data in academic oncology. DATA/SETTING: Primary/Duke Breast Cancer Clinic. DESIGN Pilot study enrolling sample of 66 breast cancer patients. METHODS Data were collected using paper- and e/Tablet-based surveys: Functional Assessment of Cancer Therapy General, Functional Assessment of Cancer Therapy-Breast, MD Anderson Symptom Inventory, Functional Assessment of Chronic Illness Therapy (FACIT), Self-Efficacy; and two questionnaires: feasibility, satisfaction. PRINCIPAL FINDINGS Patients supported e/Tablets as: easy to read (94 percent), easy to respond to (98 percent), comfortable weight (87 percent). Generally, electronic responses validly reflected responses provided by standard paper data collection on nearly all subscales tested. CONCLUSIONS e/Tablets offer a valid, feasible, acceptable method for collecting research-quality, patient-reported outcomes data in outpatient academic oncology.

Cost of multiple sclerosis by level of disability: a review of literature

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

Advanced Chronic Kidney Disease Practice Patterns among Nephrologists and Non-Nephrologists: A Database Analysis

Chronic kidney disease (CKD) outcomes, including progression to end stage, is influenced by patient treatment and is known to be suboptimal. A commercial database was analyzed to assess practice patterns and conformance to clinical practice guidelines among nephrologists and non-nephrologists who care for patients with advanced CKD (estimated GFR [eGFR] < or = 30 ml/min per 1.73 m2). Data from 1933 adults with advanced CKD on the basis of prestipulated inclusion criteria were analyzed. Individuals were designated as in a nephrologist or non-nephrologist group depending on whether a nephrologist was involved in their care. With the use of published guidelines, conformance to 10 recommendations was assessed for all patients and separately for the nephrologist and non-nephrologist groups. The average eGFR of included individuals was 23.6 ml/min per 1.73 m2. A majority were female and older than 65 yr. Non-nephrologists treated approximately half of all patients and a greater number of women and patients who were older than 65 yr. Nephrologists treated patients with a lower eGFR, equal numbers of men and women, and an equal number of individuals younger and older than 65 yr. Nephrologist conformance to guidelines was systematically better than that of non-nephrologists. These analyses reveal that a large number of patients with advanced CKD are being treated solely by non-nephrologists and that nephrologists treat patients with more advanced disease. Management of advanced CKD is suboptimal for all patients but is particularly poor for patients who are treated solely by non-nephrologists.

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

BackgroundStage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis.MethodsTwo distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression.Results342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58–1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race.ConclusionHigher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.

Quality measures for the use of adjuvant chemotherapy and radiation therapy in patients with colorectal cancer: a systematic review.

Chemotherapy (CT) and radiation therapy (RT) are essential components of adjuvant (preoperative or postoperative) therapy for many patients with colorectal cancer (CRC); however, quality measures (QMs) of these critical aspects of CRC treatment have not been characterized well. Therefore, the authors conducted a systematic review of the literature to determine the available QMs for adjuvant CT and RT in patients with CRC and rated their usefulness for assessing the delivery of quality care.

Poor Documentation Prevents Adequate Assessment of Quality Metrics in Colorectal Cancer

To standardize oncology clinical practice and improve patient outcomes, multiple organizations have developed cancer-specific metrics on the basis of a systematic background review, expert guidance, and fundamental elements of cancer care-staging and treatment.

Opportunities for Improving Management of Advanced Chronic Kidney Disease

Evidence suggests that management of advanced chronic kidney disease affects patient outcomes. To identify clinical areas that demand attention from a quality improvement perspective, we sought to examine the extent of conformance to an advanced chronic kidney disease guideline in a range of practices. A total of 237 patient medical records were abstracted from 4 primary care providers and 4 nephrology private practices across the country. In the practices studied, management of advanced chronic kidney disease patients was suboptimal for patients managed by primary care providers as well as those managed by nephrologists (overall conformance 27% and 42%, respectively), specifically for anemia, bone disease, and timing for renal replacement therapy. The current exercise (in conjunction with a literature search and focused and individual interviews with providers and patients) offered valuable information that was used to develop a toolkit for optimizing management of advanced chronic kidney disease. (Am J Med Qual 2008;23:184-192)

Utility of the Advanced Chronic Kidney Disease Patient Management Tools: Case Studies

Appropriate management of advanced chronic kidney disease (CKD) delays or limits its progression. The Advanced CKD Patient Management Toolkit was developed using a process-improvement technique to assist patient management and address CKD-specific management issues. We pilot tested the toolkit in 2 community nephrology practices, assessed the utility of individual tools, and evaluated the impact on conformance to an advanced CKD guideline through patient chart abstraction. Tool use was distinct in the 2 sites and depended on the site champions involvement, the extent of process reconfiguration demanded by a tool, and its perceived value. Baseline conformance varied across guideline recommendations (averaged 54%). Posttrial conformance increased in all clinical areas (averaged 59%). Valuable features of the toolkit in real-world settings were its ability to: facilitate tool selection, direct implementation efforts in response to a baseline performance audit, and allow selection of tool versions and customizing them. Our results suggest that systematically created, multifaceted, and customizable tools can promote guideline conformance. (Am J Med Qual 2008; 23:105-114)

What is the impact of physician communication and patient understanding in the management of headache

Migraine is a common and debilitating condition. Despite the burden of disease and increasing availability of effective treatment, migraine management is unsatisfactory. Evidence in other chronic conditions indicates that effective physician communication results in better patient understanding and health outcomes. The current literature review was intended to evaluate evidence regarding the relationship of effective physician-provider communication to health outcomes and patient satisfaction among patients with migraine. The authors searched MEDLINE® (1966–June 2007) and the Cochrane Database of Systematic Reviews for relevant publications. The search strategy combined the concepts of “headache disorders” and “physician-patient relations”. 912 abstracts were identified, and 80 (9%) of them were included for data abstraction. There were no studies that met our eligibility criteria. Therefore we revised the eligibility criteria to allow for the inclusion of non-migraine primary headache disorders or the role of non-physician health care providers. Twelve published papers met the revised criteria. The findings from the limited evidence available suggests, but does not prove, that improvements in physician-patient communication could result in a significant decrease in the burden of suffering and health care resource utilization associated with migraine. More research is needed to assess the explicit role of physician-patient communication in the management of migraine.