Hypertension is among the most prevalent chronic

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1 Switching Between Different ARBs in Patients With Controlled BP At a Glance Practical Implications e82 Author Information e86 Web Exclusive Original Research Khalid M. Kamal, PhD; Christopher Zacker, RPh, PhD; and Louis Civitarese, DO Hypertension is among the most prevalent chronic medical conditions and affects nearly 74.5 million Americans 20 years and older. 1 Hypertension is a major risk factor for cardiovascular mortality, yet only 33% of treated patients with hypertension achieve adequate blood pressure (BP) control. 2 In most patients, hypertension remains above national guidelines, increasing the risk for heart failure, stroke, coronary heart disease, and kidney failure. 3 The incremental direct medical expenditures of hypertension in the United States are estimated at $55.0 billion, 4 with additional expenditures estimated at $14 to $18 billion in indirect costs. 5 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) contains guidelines which recommend the use of thiazide-like diuretics, calcium-channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, or combination therapies as first-line treatment choices. 6 Based on clinical evidence and economic outcomes, the use of newer agents such as CCBs and ARBs has increased in recent years, and they account for a significant portion of all antihypertensive prescriptions in the United States. 7 The classic step therapy treatment paradigm of prescribing 1 drug and progressively increasing the drug s dosage to reduce BP is now considered to be inadequate in achieving BP control in most patients with uncontrolled hypertension or among those with compelling indications (eg, diabetes, heart failure, post-myocardial infarction, and chronic kidney disease). Consequently, such patients often require multiple titrations and/or combination therapy to improve BP goal attainment rates. 3,8 While such therapy modifications to achieve BP control are necessary, changes for non-medical reasons such as cost, especially among patients who are adequately controlled, should be done with caution. It is estimated that switches for non-medical (eg, formulary) reasons are more common among patients with hypertension than for ABSTRACT Objectives: To assess the impact of angiotensin receptor blocker (ARB) switching among patients with controlled blood pressure (BP) on changes in BP and BP control rates as well as physician offi ce visits and other antihypertensive medication modifi cations. Study Design: A retrospective study was conducted using the General Electric centricity electronic medical records of a primary care physician group. Methods: Hypertensive patients aged >18 years, with controlled BP (<130/80 mm Hg diabetes/renal impairment; <140/90 mm Hg all others) and receiving ARB therapy, were included. Switch must have occurred after the patient was on the fi rst ARB for at least 60 days. The nonswitch cohort also had controlled BP at baseline and remained on the same ARB throughout the study period. Results: A total of 4851 patients were given an ARB between 2004 and Switchers (n = 129) and nonswitch cohort (n = 129) with controlled BP at baseline were extracted from 714 matched pairs. Matching was done on the duration of initial ARB therapy and presence of diabetes or renal impairment. There was no difference in mean baseline SBP for switchers ( ± 13.84) and nonswitch cohort ( ± 11.37), but switchers had higher post-switch SBP ( ± 14.39) than nonswitch cohort ( ± 14.57) (P =.010). More switchers lost control from index to fi rst visit post-index period (31.8%) than control (22.5%) (P =.093), and more antihypertensive agents were added to switchers regimens (1.58 ± 1.5) than controls (0.98 ± 1.1) following the switch (P <.001). Conclusions: This study demonstrates that non-medical switches may result in loss of BP control and lead to additional medical resource use and cost. Careful consideration should be given before switching ARB therapy in patients with controlled BP. (Am J Pharm Benefi ts. 2012;4(4):e81-e87) Vol. 4, No. 4 The American Journal of Pharmacy Benefi ts e81

2 n Kamal Zacker Civitarese PRACTICAL IMPLICATIONS The study examined the clinical and economic implications of switching angiotensin receptor blocker therapy in patients with controlled blood pressure (BP). The results demonstrate that these switches may result in higher post-switch BP, possibly leading to loss of BP control and use of additional medical resources. n There is an association between switching among treatments and increase in healthcare resources and costs. n If the patient s condition is inadequately controlled after the switch, it can potentially lead to additional office visits, telephone contacts, extra tests, and discarded medications. n In the absence of clear guidelines on the practice of switching in controlled patients, careful consideration should be given to the potential benefits and costs before switching therapies. treatment of other chronic diseases. 9 However, changes to patients antihypertensive drug regimens could potentially result in loss of BP control, an increase in frequency of adverse events, and even increased treatment costs. 9,10 As the cost of medical care and prescription medicines continues to increase, formulary restrictions and increased patient cost sharing are being used with greater frequency to contain costs. As health plans and other payers negotiate rates for branded antihypertensive products, agents listed on preferred drug lists can change, resulting in products changing formulary tier and, consequently, copay amounts. Therapeutic switches without an underlying medical reason are not uncommon, even among patients who are effectively controlled with pharmacotherapy. 11,12 Although the specific rationale for these substitutions is not known with certainty, such decisions may occasionally be made from a cost perspective, without adequate consideration given to the clinical implications. From a clinical perspective, the impact of switching on treatment safety or effectiveness must be evaluated, while from an economic perspective, additional utilization of healthcare resources should be assessed. Although therapeutic switches in ARB therapy may occur due to changes in health plan formularies or drug availability, little information is available to guide these switches or to evaluate the impact of these switches on clinical and economic outcomes in an actual practice setting. The purpose of this study was to assess the realworld use of ARBs in the treatment of hypertension and the consequences, both clinical and economic, of switching between agents within the ARB class. This retrospective study uses electronic medical record data to evaluate patients who had controlled BP and yet were switched from the initially prescribed ARB to a different ARB to determine whether the new ARB provides equivalent and adequate BP control. A secondary objective was to assess whether additional medical resource utilization was observed subsequent to the therapeutic switch. METHODS Data Source Patients were retrospectively identified from the GE Centricity Electronic Medical Records (EMRs) database of a primary care physician group. At the time of the analysis, the database contained approximately 75,000 active patients receiving care from 34 primary care providers in Southwestern Pennsylvania. The EMR database allowed the capture of data from patient records including demographics and clinical diagnoses, prescribed medications, procedures, and laboratory test results. Since the data are captured at every visit, longitudinal follow-up and measurement of clinical outcomes and resource use is possible for each patient. Study Population Patients were included in the study if they were >18 years of age, had been continuously seen by the physician group, had visited a participating physician s office during the 4-year period ( ), had a recorded diagnosis of hypertension (International Classification of Diseases, Ninth Revision, Clinical Modification: 401. xx), and had initiated ARB therapy. Patients who had switched from one ARB to another ARB (index date) and remained on the second ARB for the duration of the study period (6 months) were identified. Eligible patients were required to have both a recorded BP reading on the index date and a subsequent measurement during the follow-up period. Patients with only 1 observation either before or after the index date were excluded from the study. Switchers were identified as those patients who had switched from one ARB to a different ARB. Switching from an ARB to an ARB/hydrochlorothiazide combination was not considered to be a switch unless the ARB component differed. Patients were required to have had an initial ARB prescribed for them for at least 60 days before the switch to a different ARB occurred. The selection of this time period (60 days) was based on the assumption that a patient would be stabilized on the first ARB during this time period, thus offering some assurance that the switch did not occur due to intolerance. The nonswitch cohort consisted of patients who remained on the same initial ARB therapy and did not switch. To reduce the potential influence of confounding variables, e82 The American Journal of Pharmacy Benefits July/August 2012

3 Switching Between Different Angiotensin Receptor Blockers Figure. Study Time Frame 2004 to 2008 BP closest to index date used for baseline First BP reading after index date (6 months) 6 months Index date 6 months BP indicates blood pressure. Baseline or pre-index reading was the most recent reading prior to the switch and post-index reading was the first reading after the switch within 6-month period. BP control was defined as BP of <140/90 mm Hg for all patients except <130/80 mm Hg for diabetic patients or those with renal conditions. the nonswitch cohort was matched with the switchers on the duration of initial ARB therapy and the presence/ absence of diabetes or a chronic kidney condition. The date of the ARB switch was identified as the index date for switchers. The index date for the nonswitch cohort was the matched index date with the switchers with a 2-month window in duration to allow easier matching between the 2 cohorts. Two 6-month periods were then identified around the index date: a 6-month pre-period and a 6-month follow-up period to capture clinical and economic outcomes (Figure). Study Outcomes The outcomes of interest included systolic (SBP) and diastolic blood pressure (DBP) measurements at baseline (pre-index) and post-index, number of office visits (postindex), and addition of other non-arb antihypertensive medications (post-index). At least 2 valid BP readings were required for each patient, with baseline or pre-index reading being the most recent reading prior to the switch and post-index reading being the first reading after the switch. BP Control was defined as BP of <140/90 mm Hg for all patients except <130/80 mm Hg for diabetic patients or those with renal conditions. Based on the changes to SBP and DBP, the percent of patients that lost BP control, gained BP control, or maintained the same BP control status from index to first visit post-period was calculated. In addition, the mean number of non-arb antihypertensive agents added in the post-index period for switchers and nonswitchers, and the number of office visits during the post-index dates, were measured. A number of other demographic and clinical variables such as age, gender, and presence of comorbid conditions (eg, diabetes and renal conditions) were included in the analyses for statistical control. Statistical Analyses Descriptive statistics were conducted across the 2 cohorts. Independent t tests were employed for comparisons of continuous variables, such as BP measurements and the number of office visits. χ 2 tests were used to compare categorical variables, such as changes to antihypertensive therapy before and after the switch, compared with the nonswitch cohort. Additional analysis using covariance (ANCOVA) with controlled potentially confounding factors such as age, gender, patient s diabetes and renal status, and numbers of days patients were on ARB was conducted. Data from the EMR database were extracted using Microsoft SQL, and all statistical analyses were conducted using SPSS version 18.0 (SPSS Inc, Chicago, Illinois). A P value of <.05 was considered statistically significant. The study was approved by the Institutional Review Board at Duquesne University (Pittsburgh, Pennsylvania). RESULTS Initial review of the EMR database identified 4851 patients with hypertension who were given an ARB between 2004 and A total of 656 (13.52%) patients were switched from one ARB to another, for any reason, during that time period. Based on the inclusion/exclusion criteria, 357 matched pairs of switchers and nonswitchers were identified using a 1:1 matching based on the duration of ARB treatment and the presence/absence of diabetes/renal condition. The mean age of the switchers was years and the nonswitch cohort was years (P <.001). Overall, 62.2% of the switchers were females compared with 58.0% of the nonswitch cohort (P =.252). The 2 cohorts were comparable on base days (numbers of days patients were on ARB), prevalence of diabetes or renal conditions, and pre-index SBP. Since the goal of the study was to assess the impact of ARB switch on changes in BP, switchers (n = 129) and their matched control nonswitchers (n = 129) who had controlled BP at baseline (<130/80 diabetes/renal impairment; <140/90 all others) were extracted from the 357 matched pairs. There were no statistically significant differences between the 2 groups in the duration of the ARB Vol. 4, No. 4 The American Journal of Pharmacy Benefits e83

4 n Kamal Zacker Civitarese Table 1. Patient Characteristics for the Subset of Patients With Controlled Blood Pressure at Baseline (n = 258) Switchers Nonswitch Cohort P N Age (mean ± SD) ± y ± y a Gender Male 53 (41.1%) 47 (36.4%) b Female 76 (58.9%) 82 (63.6%) Base days ± ± a Diabetes or renal condition Yes 30 (23.3%) 24 (18.6%) b Base days indicates numbers of days patients were on angiotensin receptor blocker therapy; SD, standard deviation. a Independent t test, P <.05. b χ 2 Test, P <.05. treatment and the presence/absence of diabetes/renal condition (Table 1). The mean age of the switchers was years and the nonswitch cohort was years (P =.232). Overall, 58.9% of the switchers were females compared with 61.9% of the nonswitch cohort (P =.443). Table 2 details the baseline SBP and DBP, loss of BP control in the post-index period, and changes in resource utilization (post-index) in patients who had controlled BP at baseline (univariate analysis). There was no difference in mean baseline SBP for switchers ( ) and nonswitch cohort ( ) but switchers had higher post-switch SBP ( ) than nonswitch cohort ( ) (P =.010). More switchers lost control from index to first visit post-index period (31.8%) than control (22.5%), although this finding was not statistically significant (P =.093). In the post-index period, more non-arb antihypertensive agents were added in switchers ( ) than control ( ) Table 2. Study Outcomes Among Patients With Controlled Blood Pressure at Baseline [Univariate Analysis] (n = 258) Switchers Nonswitch Cohort P SBP (mean ± SD) Pre-index ± ± Post-index ± ± a DBP (mean ± SD) Pre-index ± ± Post-index ± ± Stayed the same b 88 (68.2%) 100 (77.5%).093 Lost control c 41 (31.8%) 29 (22.5%).093 Other antihypertensive medications Post-index 1.58 ± ± a (mean ± SD) Office visits (mean ± SD) Post-index 2.91 ± ± DBP indicates diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation. a Independent t test, P <.05. b Stayed the same: a patient was considered to have stayed the same if the blood pressure readings remained high to high or low to low. c Lost control: a patient was considered to have lost control if the blood pressure readings went from low to high. (P <.001). Also, switchers had a slightly higher number of postindex office visits ( ) compared with the nonswitch cohort ( ), but the difference was not statistically significant (P =.239). Adjusted means and confidence intervals (CIs) for post-switch SBP and DBP and post-index changes in resource utilization from ANCOVA analysis after controlling for influencing factors such as age, gender, patient s diabetes and renal status, and number of days patients were on ARB are reported in Table 3. Switchers had higher post-switch SBP ( ; 95% CI ) than nonswitch cohort ( ; 95% CI ) (P =.019). There was no significant difference in post-switch DBP between switchers ( ; 95% CI ) and nonswitch cohort ( ; 95% CI ) (P =.525). In the post-index period, more non-arb antihypertensive agents were added in switchers ( ; 95% CI ) than control ( ; 95% CI ) (P <.001). There was no significant difference in post-index office visits between switchers ( ; 95% CI ) and nonswitch cohort ( ; 95% CI ) (P =.798). Table 4 reports the results from a paired sampled t test that provides the within-group changes in pre- and post-index SBP and DBP. Although both groups showed an increase in the SBP, the increase in SBP (as reported by mean differences) was higher for switchers (6.388; P =.001) compared with the nonswitch cohort (2.946; P =.025). For DBP, the mean differences for switchers was statistically significantly different (1.829; P =.025) whereas the pre- and post-differences were not statistically significant for the nonswitch cohort (1.481; P =.107). DISCUSSION This study examined the clinical and economic implications of switching ARB therapy in patients with controlled BP. The results demonstrate that e84 The American Journal of Pharmacy Benefits July/August 2012

5 Switching Between Different Angiotensin Receptor Blockers Table 3. Post-Index Study Outcomes Among Patients With Controlled Blood Pressure at Baseline [ANCOVA Analysis] (n = 258) switching patients who have controlled BP may result in higher post-switch BP, possibly leading to loss of BP control and use of additional medical resources. The JNC 7 recommends regular monitoring and follow-up of patients initiating new antihypertensive medications until their BP goals are achieved. 3 Since clear guidelines do not exist on therapeutically equivalent and interchangeable doses of different ARBs, patients who have switched ARB therapy may still require additional follow-up for dose titrations or additional antihypertensive agents, leading to the increased medication use and office visits observed in this study. Few studies have been reported in the literature that evaluated the clinical and economic impact of switches within the ARB class. Even though this study did not quantify the economic consequences of additional antihypertensive medications and office visits, other ARB-related studies have shown that switching medications can apparently affect clinical outcomes and the unintended economic consequences may go beyond the drug acquisition costs alone Usher-Smith and colleagues (2007) in the United Kingdom assessed the cost savings and patients perspective of switching patients (n = 115) from losartan to candesartan. 11 At the end of the study, 7 patients switched back to losartan and among those that stayed on candesartan, there was a slight reduction in BP with no adverse events attributable to the switch. The annual savings was estimated at 13, However, the authors cautioned that individual patients attitudes should be carefully considered by physicians prior to switching, since many of the patients were reportedly annoyed at the idea of switching between drugs. 11 Graham and Allcock (2002) evaluated the clinical outcomes in patients who were switched from losartan or valsartan to irbesartan. 12 Mean BP before and after the switch was similar in patients during the conversion process. Also, no serious adverse events were reported, although a higher number of patients (34 out of 79) discontinued irbesartan due to the incidence of adverse events. 12 An administrative claims database study by Signorovitch and colleagues (2010) estimated that patients who were switched from valsartan Adjusted Mean ± SD CI (95%) P SBP Switcher ± a Nonswitch ± DBP Switcher ± Nonswitch ± Other antihypertensive medications Switcher 1.58 ± a Nonswitch 0.98 ± Office visits Switcher 2.77 ± Nonswitch 2.69 ± CI indicates confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation. ANCOVA analysis: controlled for age, gender, base days, and presence/absence of diabetes or renal conditions. a Significant at P <.05. to other ARBs without any medical reasons incurred 19.1 additional outpatient visits per 100 patients, 9.3 additional hypertension-related inpatient days per 100 patients, and a higher medical cost of $748 per patient compared with $492 per patient for nonswitchers. 13 Another claims-based analysis of a US managed health plan s enrollees demonstrated that switching among ARBs was associated with a statistically significant greater all-cause health services cost than those who remained on the same ARB medication ($6286 vs $5701, respectively). 14 A survey of healthcare providers in a long-term care setting highlighted the concerns about non-medical switching that were based on formulary restrictions. 9 Nurses, pharmacists, and physicians reported that switching was common in patients with hypertension, and the practice of switching was perceived to increase administrative time, side effects, and overall risk of costly outcomes. 9 If the patient s condition is inadequately controlled after the switch, it can potentially lead to additional office visits, telephone contacts, extra laboratory and diagnostic tests, discarded medications, hospital and emergency department visits, and even loss of productivity. 10 The association between switching among treatments and increase in healthcare resources and costs has also been reported for statins, antidepressants, and antiepileptics. 13 These findings highlight the challenges and potential pitfalls in implementing cost-control mechanisms, such as tiered pharmacy benefits, that strive to achieve healthcare cost savings by influencing patient cost-sharing to drive patients toward less costly agents. While savings may be engendered on the impacted prescription product, it is worth considering that savings generated may be more than offset by increased healthcare costs. In the absence of clear guidelines on the practice of switching in patients who are controlled, careful consideration should be Vol. 4, No. 4 The American Journal of Pharmacy Benefits e85

6 n Kamal Zacker Civitarese Table 4. Study Outcomes Among Patients With Controlled Blood Pressure at Baseline and Post Index [Within-Group Differences] (n = 258) Mean ± SD Mean Difference CI (95%) P Switcher Baseline SBP ± SBP at post index ± a Baseline DBP ± 9.05 DBP at post index ± a Nonswitch Baseline SBP ± SBP at post index ± a Baseline DBP ± 9.22 DBP at post index ± CI indicates confidence interval; DBP indicates diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation. Paired sample t test. a Significant at P <.05. given to the potential benefits and costs before switching therapies. Several factors should be taken into account before making these switches: with respect to withinclass substitution, evidence on the effectiveness, safety, and different indications for different ARBs needs to be carefully considered. 10 Reports on the clinical effectiveness of different ARBs in patients with hypertension are mixed. Two meta-analyses reported no differences in the BP-lowering effects of different ARBs 15,16 while a third study showed significant differences between ARBs. 17 In addition, the indications vary among agents in the ARB class, making it important for clinicians to base their prescribing decisions on patient comorbidities and clinical evidence rather than on the assumptions of effectiveness and safety equivalency of different ARBs. 10 The results of our study should be interpreted in the context of the real-world data used in the study. The main limitation is that our results are based on a patient population and data of 1 physician group from a limited geographical area, and may not be generalizable to other populations or even those practices that do not have EMR. In addition, there may have been differences in the evaluation of patients by different providers within the practice itself or differences in the availability and cost of different ARBs available on local managed care formularies. Second, patient adherence and persistence with medications could not be assessed in our retrospective analysis using EMR data. Although it is well established that poor adherence results in additional resource use and costs, the impact of switching on patient adherence and persistence has been largely ignored. The reported use of the medications by the patients actually reflects the prescriptions written by the physicians, and thus the initiation of the therapy is assumed. Any assumption regarding differences in clinical outcomes due to differences in patient adherence rather than efficacy reflects the real-world practice. Third, the use of a single pre- and postindex BP measurement could be a limitation, and alternatives (such as multiple measurements) could produce differing results. However, given the structure of the EMR database and comparison of 2 groups, the use of single pre- and post-index BP measurement was considered a consistent measure. We were unable to ascertain the reason for each switch, and the assumption was made that switches resulted from formulary-related considerations; it is difficult to know the impact of this assumption or how this may have affected our study s findings. Some important information was not available for analysis, such as duration of hypertension, number and severity of all cardiovascular-related comorbid conditions, use of other medications which may affect BP, and patient body mass index, and it is difficult to know the role these covariates may have played in BP control. Nevertheless, our study provides useful information regarding the potential impact of switching from one ARB to another agent within the class. In summary, careful consideration should be given before switching patients with controlled BP between drugs within the same antihypertensive class, with such switches warranting the same consideration as any other change in medication regimen. Our study demonstrates that switching in controlled patients may result in unintended clinical and economic outcomes. Author Affiliations: From Department of Pharmacy Administration (KMK), Duquesne University, Mylan School of Pharmacy, Pittsburgh, PA; Novartis Pharmaceuticals Corporation (CZ), Emmaus, PA; Preferred Primary Care Physicians (LC), Oak Manor, Pittsburgh, PA. Funding Source: The study was sponsored by Novartis Pharmaceuticals Corporation. Author Disclosures: Dr Zacker reports employment and stock ownership with Novartis Pharmaceuticals Corporation, the funder of the study. The other authors (KMK, LC) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. Authorship Information: Concept and design (KMK, CZ, LC); acquisition of data (KMK, LC); analysis and interpretation of data (KMK, e86 The American Journal of Pharmacy Benefits July/August 2012

7 Switching Between Different Angiotensin Receptor Blockers CZ, LC); drafting of the manuscript (KMK, CZ); critical revision of the manuscript for important intellectual content (KMK, LC); statistical analysis (KMK); provision of study materials or patients (KMK, LC); obtaining funding (KMK, CZ); administrative, technical, or logistic support (KMK); and supervision (KMK, CZ). Address correspondence to: Khalid M. Kamal, PhD, 418 B Mellon Hall, Mylan School of Pharmacy, 600 Forbes Ave, Duquesne University, Pittsburgh, PA kamalk@duq.edu. REFERENCES 1. American Heart Association. High blood pressure statistics. Accessed October 29, Ong KL, Cheung BM, Man YB, Lau CP, Lam KS. Prevalence, awareness, treatment, and control of hypertension among United States adults Hypertension. 2007;49(1): Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension. 2003;42(6): Balu S, Thomas J III. Incremental expenditure of treating hypertension in the United States. Am J Hypertens. 2006;19(8): Hodgson TA, Cohen AJ. Medical care expenditures for selected circulatory diseases: opportunities for reducing national health expenditures. Med Care. 1999;37(10): US Department of Health and Human Services. National Heart Blood and Lung Institute. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. guidelines/hypertension/jnc7full.pdf. Published August Accessed September 4, Pickering TG. Advances in the treatment of hypertension. JAMA. 1999;281(2): Bakris GL. A practical approach to achieving recommended blood pressure goals in diabetic patients. Arch Intern Med. 2001;161(22): Cote BR, Petersen EA. Impact of therapeutic switching in long-term care. Am J Manag Care. 2008;14(11 suppl):sp23-sp Johnston A, Stafylas P, Stergiou G. Effectiveness, safety and cost of drug substitution in hypertension. Br J Clin Pharmacol. 2010;70(3): Usher-Smith JA, Ramsbottom T, Pearmain H, Kirby M. Evaluation of the cost savings and clinical outcomes of switching patients from atorvastatin to simvastatin and losartan to candesartan in a primary care setting. Int J Clin Pract. 2007; 61(1): Graham MR, Allcock NM. Irbesartan substitution for valsartan or losartan in treating hypertension. Ann Pharmacother. 2002:36(12): Signorovitch J, Zhang J, Wu EQ, et al. Economic impact of switching from valsartan to other angiotensin receptor blockers in patients with hypertension. Curr Med Res Opin. 2010;26(4): Thayer S, Dastani H. Can switching among the ARB class impact medical costs and medication adherence? Abstract from poster presented at AMCP s 21st Annual Meeting & Showcase. J Manag Care Pharm. 2009;15(2): Baguet JP, Legallicier B, Auquier P, Robitail S. Updated meta-analytical approach to the efficacy of anti-hypertensive drugs in reducing blood pressure. Clin Drug Investig. 2007;27(11): Conlin PR, Spence JD, Williams B, et al. Angiotensin II antagonists for hypertension: are there any differences in efficacy? Am J Hypertens. 2000;13(4, pt 1): Nixon RM, Muller E, Lowy A, Falvey H. Valsartan vs other angiotensin II receptor blockers in the treatment of hypertension: a meta-analytical approach. Int J Clin Pract. 2009;63(5): Vol. 4, No. 4 The American Journal of Pharmacy Benefits e87