ee cone rcs Predictors of Adherence With Antihypertensive and Lipid-Lowering Therapy Richard H. Chapman, PRD; Joshua S. Benner, PharmD, SeD; Allison A. Petvilla, BA: Jonothan C. Tierce, CPhil S. Robert Collins, BS; David S. Battleman, MD; J. Sanford Schw Background: Patients with comorbid hypertension and dyslipidemia are at high risk for cardiovascular disease, which can be considerably mitigated by treatment. Ad hherence with prescribed drug therapy ts, therefore, es- pecially important in these patients, This study was un- dertaken to describe the patterns and predictors of adherence with concomitant antihypertensive (AH) and lipid-lowering (LL) therapy Methods: This retrospective cohort study examined 8406 enrollees in a US managed care plan who initiated treat ment with AH and LL therapy within a 90-day period Adherence was measured as the proportion of days cov cred in each 3-month interval following initiation of con- comitant therapy (mean follow-up, 12.9 months). Pa- tients were considered adherent if they had filled prescriptions sullicient to cover atleast 80% of days with sartz, MD Results: The percentage of patients adherent with both AH and LL therapy declined sharply following treat- ment initiation, with 44.7%, 35.9%, and 35.89% of pa- tients adherent at 3, 6, nd 12 months, respectively. A ter adjustment for age, sex, and other potential predictors, patients were more likely to be adherent if they initiated AH and LL therapy together, had a history of coronary heart disease oF congestive heart failure, oF took fewer ‘other medications. Conelusions: Adherence with concomitant AH and LL therapy fs poor, with only 1 in 3 patients adherent with both medications at 6 months. Physicians may be able to significantly improve adherence by initiating AH and LL therapy concomitantly and by reducing pill burden. both classes of medic model evaluated potential predictors of adherence Arch Intern n Med. 2005;165:1147-1152 Author Affiliations ValueMedics Research, LLC, Arlington, Vs (Des Chapman snd Benner, Ms Pts, and Mr Tiece); Waratah Corporation, Durham, NC (Q4r Collins) Department of Outcomes Research, Pier Inc, [New York, NY (Dr Batteman): Leonard Davis Institute of Health Economics (Ds Bateman and Sehwart2) and Division of General, Internal Medicine, Department ‘of Medicine, School of Medicine snd Health Care Systems Department, Wharton School (Dr Schwan), University of Pennsylvania, Philadelphia Financial Disclosure ValueMedics Research, LLC, has received payments for research snd consulting from Pier Ine tnd Dr Schwartz has received research support fom and does ‘consulting for Plizer In. ARDIOVASCULAR DISEASE (Cvb) accounts for inex- cess of 930000 deaths and $350 billion in di rect medical costs and lost productivity in the United States each year-' Numerous clinical tials and met analyses have concluded that antihypes tensive (AH) and lipid-lowering (LL) medications substantially reduce the risk of coronary heart disease (CHD), stroke, and death in patients with CVD risk fac tors,**with long-term therapy yielding the sgreatest benefit" In actual practice, however, long: adherence and persistence with pr seribed drug therapy are poor. Of all wri ten prescriptions, 14% are never filled and another 13% are filled but never taken.” ‘Among patients who actually i therapy with 3-hydroxy-3-methylglu- taryl coenzyme A reductase inhibitors (statins), observational studies'**have re- ported 1-year discontintation rates of 15% to 60%, depending on the patient popu- lation, practice setting, and year of study. Among low-income elderly patients, only 2696 were sil taking statins regularly 5 years after initiating therapy. similar trends have been observed with AH medi- cations. Daring the first year of AH ie ment, the average elderly patient had filled AH prescriptions less than 50% of the Uime'* and only 1 patient in 5 exhibited compliance sufficient to obtain the thers- peutic benefits observed in clinical trials." Many’ patients have both hyperten- son and dyslipidemia." The presence of both of these cardiovascular risk factors places patientsat substantially greater isk of CHD events than either condition alone. In these patients, adhe: concomitant AH and LL therapy is espe- cially important However, adherence with concomitant therapy is not well unde stood, because previous studies have ex- amined persistence with single-drug clases. The objectives ofthis study were 19 (1) suudy the pattern of adherence with con- ence with, (©2003 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017comitant AH and LL therapy in a US managed care popu lation and (2) identify patient and regimen characteris- tics that predicted optimal adherence with concomitant therapy. 2s} PATIENTS “This retrospective cohort study examined enrollees ina US man- aged care organization from Janusty 1, 1990, unl April 30, 3001, Data were retrieved from a computerized databace (the BrotocareScencts Managed Care Database) of filled prescrp- ton records and pad claims for medical services and proce lures ll patient Kenifiers were removed before analysis 0 ‘maintain patent confident and to sdher to Health infor: Imation Portability and Accountability Act of 1900 sandards fd requirements ‘Allentolles who initiated AH or LL prescription dry therapy between January 1, 1097, and Janary 30" 2001, and ‘were continuously ligible for pharmacy benefits throughout nrolment were Mentiid. The analysis was restricted to new ‘users by requiring that patients had no illed prescriptions for the relevant drug class during the prior 12 months, New users Of AH medications were seo required tobe diagnosed as hav- {ng hypertension belor ination of therapy, becase many AH medications are used fr other indications “To dently new stars of concomiant therapy, only those patents who inated treatment with both AH and LL therapy ‘thina S0ay window were analyzed. 90-day window was Selected to minimize the possiblity that patients would have income nonadherent with the AH treatment before inating Li therapy. and vice versa, Patients were reaied in the analy sis rom the ist dat of concomitant therapy (the index date) tinul death, disenrollment rom the healt plan, or April 30, 3001, whichever occurred fist. OUTCOME MEASURES Adherence with AHalone, LI alone and oth AH and LL was fneasured in 9-day intervals rom the index date. Adherence thas defied an the proprtnn of dejo covered bya given dg {lassi each ime interval based om number of days supplied Snd quantity of mediation dapensed for each tilled prescrip tion "An imputed value for days supplied was used if miss ingor ifthe quantity dispensed divided by the days supplied yictled an implausible dy dosing frequency (0.32 fr sta dns.05-6 lor other drgn 03-4 or AH medion). The imputed yalue was based onthe modal diy desing requeney foreach drug This imputation sigrithm flected less than 1 othe patent intervals in our ile. A day was assumed tobe over ifany AH orLL drug was avalble. Ths estimates of fcherence represented an upper bound onactal adherence with rescribed therapy Patents were cased a adherent if they [oan indicatonspeiic proportion of days covered of 80% cormore ina given 9t-day interval, consistr with other stad itso of drug adherence Patents were considered adherent fvth concomitant therapy fat east 80% of days were covered Ty both Adv and LL drug POTENTIAL PREDICTORS OF ADHERENCE WITH CONCOMITANT THERAPY ‘To identify potential predictors of adherence with concomi- lant AH and LL therapy. we examined aset of demographic (eg, age and sex) and clinical (eg outpatient diagnoses, medical pro- (aernoyteD) ARCHINTERN WEDVOE TS, cedures, and prescriptions filled during the 365 days before the index date) characteristics that have been observed previously toalfect adherence with prescribed medication use for chronic conditions." Patients who ad evidence of pretreatment CHD ‘were categorized into 3 groups: (1) angina or coronary ang ‘ography; (2) coronary artery bypass graft, percutaneous tra luminal coronary angioplasty, or history of CHD: and (3) acute ‘or prior myocardial infarction.” Patients who met the criteria for more than one group were assigned tothe highest category whose criteria they mel. Other comorbid conditions assessed included history of stroke, congestive heart failure, diabetes mellitus, depression, and dementia. Health services use was also assessed based om the year be- fore initiating concomitant therapy, and included frequency of hospitalizations, frequency of outpatient physician visits, and number of medications prescribed. After examining the distr- butions ofthese measures, it was determined that hospital tion would be analyzed ava inary covariate, while the num- ber of physician vists would be analyzed in quartiles STATISTICAL ANALYSIS “The mean, median, and interquartile ranges for proprton of days covered were cleulated foreach dg indication (AH or LU} and for concomitant therapy (AH and LL). The propor: tin af patients classified a adherent in each 9-day interval twas determined for concomitant therapy and for AM and UL Unugs separately. Siguicant predictors ofadherence with con- omfin! herp werden sing generale Rn mod- itor repented measures to estimate the probably that Subject had at least 80% of days covered by both AH and LL therapy each interval The decline in perience ove ime {im months) was assumed oe linear onthe log cle Totenial predictors of adherence were constlered sats cally sigicintat P= 03-The inal malivariate model was ad sted fortime sinc the index date and foal the characters tesprvitny te Altay attics were efor ing, commercial sealable software program (SPSe 13 SPSS Ine Chicago, andthe mulvariate mol was ited ting SAS Satin soliware, version 802 (SAS fst Ine, Cary. NO). EES} POPULATION CHARACTERISTICS A total of 8406 concomitant AH and LL therapy users met study inclusion criteria. Patients were followed up for an average of 12.9 months (range, 3-36 months). Of the patients, 33.0% initiated concomitant therapy on the same date, while 36.79%, 16.0%, and 12.7% initiated AH. and LL therapy within 1 to 30, 31 t0 60, and 61 to 90 days, respectively “Approximately half of patients were younger than 65 ‘on the dave that they initiated concomitant therapy, and half were women (Fable 1). In the year before their in- dex date, 2.5% of patients had evidence of angina or coro- nary angiography, 18.2% underwent prior percutane- ous transluminal coronary angioplasty, prior coronary artery bypass grafling or treatment for chronic CHD, and 11.0% experienced or had a history of an acute myocar- dial infarction. Most patients (68.3%) had none of these CHD-related diagnoses or procedures, Diabetes melli- tus was the most prevalent comorbid condition, fol- lowed by stroke (Table 1). (©2003 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017PATTERNS OF USE OVER TIME The percentage of patients adherent with both AH and LL therapy (Figure) declined sharply following treat- ment initiation, with 44.7%, 35.9%, and 35.8% of the population adherent at 3, 6, and 12 months, respec- lively, after which adherence generally stabilized. In each time interval examined, an additional 25.3% to 29.6% of | patients were adherent with either AH of LL therapy, but not both, Relatively few patients were adherent with LL therapy and nonadherent with AH therapy (Figure). The proportion of patients who were nonadherent with both Adland LL medications increased from 27.4% a3 months 10 35.0% at 6 months, and reached its maximum of 39.0% after 27 months. PREDICTORS OF ADHERENCE WITH CONCOMITANT AH AND LL MEDICATIONS Alter adjusting for age, sex, and other measured vari- ables, the strongest predictor of adherence with con- ccomitant therapy was the number of other prescription, medications taken in the year before initiating concomi- tant therapy (Table 2). As the number of other pre- scribed medications decreased, the likelihood of adher~ cence with concomitant AH and LL therapy increased. For ‘example, patients taking no other medications were ap- proximately twice as likely tobe adherent with concomi- lant therapy as those taking 6 oF more other medica- The second strongest predictor of adherence with con- comitant AH and LL therapy was age. Adherence was greatest among patients aged 55 to 64 years, followed by those aged 65 to 74 and 45 to 54 years. Sex also was a significant predictor of adherence, with women less likely to be adherent than men, Time between initiation of AH and LL therapy was the third strongest predictor of adherence. Patients who started these regimens on the same day or within 1 month, ofeach other were 34% (95% confidence interval, 18%- 52%) more likely to be adherent with both medications during the 3-year study period, compared with patients who initiated therapy 2 to 3 months apart, Time since initiation of concomitant therapy also was a strong pre- dictor of nonadherence. The adjusted odds of being ad- hherent with concomitant therapy declined by 14% for ev- ery unit increase in months (on a natural log scale) following treatment initiation. For example, 14.3% fewer patients were adherent at 2.75 months than at 1 month (og.(2.75]=1). Patients with a higher CVD risk at baseline were gen- erally more adherent than those without CVD risk fac~ tors (Table 2).For example, patients with history ofacute ‘or prior myocardial infarction inthe year preceding treat- ment initiation had 28% greater odds of adherence than those without any evidence of CHD. However, a history of diabetes mellitus, a diagnosis of angina, ora history of coronary angiography without revascularization or myo- cardial infarction was not associated with significantly im- proved adherence. Patients who had been hospitalized at least once for any cause in the pretreatment year were slightly less likely to be adherent over time. ‘Table 1. Characteristies of 8406 Patients Who Initiated Both Lipid-Lowering and Antihypertensive Drug Therapy Within, ‘90 Days of Each Other ete Demographics ‘a. ez ar ut a9 aed 65 2554 199 5564 na en 5 rsa 189 285 18 Feral sox 469 Cine history forthe year bore the index date Coronary artery disease Lave (nga or eoronary anglogashy) 25 Lave 2 (CHD, CABG, o PTCA) 182 Love acta Ml) na Soke a5 Congestive eat talure 15 Depression 50 Dement 12 Diabetes mets 28 (halen comarbiy ndext 90 1.26) Heath services inthe yar before the index date No.of prescription mediatonst 296,391) No.of eutpatntpystianstst 00417) Hospital 8 ‘Abreviations: CABG, coronary arary bypass grat CHO, coronary heat dessa Ml, myocardial ron; PTCA, peretaneou anlaminal ‘onary angsty “Daa ate gven as percentage of paints unless otherwise inate, Daa are gn as mea (50), Le} —_ This study, one of the first to empirically estimate pat- terns and predictors of joint long-term adherence with ‘AH and LL medications, demonstrated that less than hall ‘of patients (44.7%) were adherent with both AH and LL therapies 3 months alter medication initiation, a figure that decreased to 35.8% at 12 months, However, at each time point, an additional 25.3% to 20.6% of patients wer adherent with either AH or LL therapy. Adherence with, [AH therapies was, on average, approximately 10% to 15% ‘greater than with LL medications over time. ‘Age was a strong predictor of adherence with con- comitant AH and LL therapy. Women were less adhe ‘ent than men. After adjusting for age, sex, and other mea- sured variables, the initiation of AH and LL therapy: together, a history of CHD or congestive heart failu and taking few other medications also were demon- strated to predict adherence with concomitant AH and LL therapy. ‘Of the patients in this concomitant therapy cobor 17574 (00.1%) were between the ages of 45 and 84 years. All descriptive analyses and the multivariate model we therefore, repeated within this subset of patients. The r sults of the descriptive analyses and the patterns of ad- herence mirrored those found in the entire cohort, Thes (©2003 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017wioaiirat [Bade L Thy anos A Thay {aAbeTa AH Then nd Nomar LL Thea Dade Ld A Thay ‘wetPane eeeeteezess a a % Tina Sch inde Dt, mo Tonle Pans OG 2086S 50 ARATE aS Sms inubaen 274 S80 959 883 SIA DROSS AdncolL Reape aTry) 25725-6557 SSB T8783 588 Adnactom Tey a Nenahemtol Tay) 124 219 21D A BE BA I I mS wo BE amt MiwmoLLand ating) M7 380M OGG NSS ZO 2 Figur, Paterno aon adherence wo concomiant therapy oer 3 yeas The inated. Pecontagos at each ate rmay at tol 100 bacaus of rounding AH i analyses also were repeated within the same subset of pa- tients aged 45 to 84 years, with results stratified by whether patients were younger than 65 years or 65 years and older. ‘While patients 65 years and older tended to have higher rates of comorbidity and health services use, no striking differences in patterns of compliance with AH or LL medi- ccalions were observed between subjects younger than 65 years and those 65 years and older. The patiern of adherence observed in this study—a, sharp decline in the first 6 months, followed by a more ‘gradual decline over time—is consistent with previous Tongitudinal studies?" of adherence with AH or LL, therapies. However, the rates of adherence observed in this study with concomitant AH and LL therapies, and ‘with AH or LL therapy alone, were higher than those re- ported in previous studies!" that assessed adherence to either AH of LL medications. This difference may indi- cate the greater motivation to be adherent with therapy among patients who had multiple cardiovascular risk f8c- tots, a finding reported in previous studies" of drug adherence in patients with hypertension and dyslipid- emia. The higher adherence in our study may also be re- lated to the nature of the population studied, namely, a commercially insured cohort with pharmaceutical in- surance. Higher rates of adherence have been observed. previously in commercially insured populations." The sharp decline in adherence observed in the first ‘6 months afler initiation of therapy for AH and/or LL and, the low overall rate of adherence to concomitant therapy fare major concerns. Recent studies" using meta- analysis and treatment algorithms have suggested that sub- stantial reductions in the risk of cardiovascular events may be obtained by simultaneously targeting hyperten- sion and dyslipidemia. Intensive treatment of modi able cardiovascular risk factors reduced the risk of ear diovascular and microvascular events by about 50% in patients at high risk of CVD, stich as those with type 2 diabetes mellitus and microalbuminuria Thus, improv- ing adherence with concomitant AH and LL therapy will result in substantial health care benelits Tad date was dined as th data concotant therapy (i, cond dug) wat inate antnypenensive LL poring, The data obtained concerning predictors of adher- cence have potential to guide efforts and interventions for improving patient adherence with prescribed AH and LL medication. For example, the observation that approxi- mately one-fourth of the study population was adherent with one medication (usually AH therapy) but not the other demonstrates receptivity to, and partial adhei cence with, drug therapy to prevent CVD. Therefore, the potential exists for improved adherence with concur- rent AH and LL therapies. Any ellective intervention among these partially adherent patients may potentially double the percentage of adherent concomitant AH and LL therapy users, ‘Adherence declined most rapidly during the first 6 months of concomitant AH and LL therapy, suggesting the importance of early interventions to maintain or im- prove adherence. Similarly, adherence was best when AH and LL therapies were initiated on or about the same date, “suiggesting benelit from concomitant initiation of therapy to treat these 2 cardiovascular risk factors, The number of other medications a patient was tak- ing in the pretreatment year was strongly and inversely associated with adherence with concomitant therapy, con- sistent with previous studies" of the association be- tween the total number of medications administered and adherence with prescribed cardiovascular medications. Studies have suggested that simplifying a drug regi- men by eliminating even one pill (by using a fixed-lose combination AH product instead of 2-pill combination, therapy) could improve adherence. Randomized clini- cal trials” assessing the utility of combined AH and LL therapy in the treatment of concomitant hypertension and dyslipidemia have been completed and will provide fur~ ther guidance on this issue. ‘Our results should be interpreted in light of study lini- tations. First, the use of proportion of days covered may overestimate adherence, because it assumes that pa- tients take all of the medications for prescriptions that are filled, This method may also have overestimated ad- herence in patients prescribed AH regimens consisting (©2003 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017Table 2. Predictors of Adherence With Concomitant AH and LL Medications Uraaistea Ren ‘Aajusto Ress? vara Seas mato 5%scH) Pane —_—badsRati (oct) Val {ine bewoon ea of Aland LL heap 020 152(130-156) 34118152) 21-60 074056082) ‘109 04127), 1.00 085 058.75) 4.00} “ie sine ths natn of concomitant harap, lag (no) 087 (084.000) 085(082.080) Damagaphics Bony neat 073 053.088) +00 1556 0.95 086-105) 1124(105-147) 5556 tasi21-148) 115613018), ere 1.00 (092-108) 127 (108149), 215 087 0.70.06) 1.18 0.95136), Female soc 085 070.052) 191 (0-098) incl istry in th baseline year Coronary arr sense None 087 80.098) S004 NA Lave (angina or eoranary angiography) 083 054-08) 95 074120) 7a Lowel 2 (PTCA, CABG, chron CHO) 115 (105-1.29), 20 (107138) m1 Loe 3 (acute 115 (102-130) 1128(1.00150), 03 sole 110(097-125) 120(104139), Congestive heart flue 122(106-140) 1128(105-148) 08 Depression 083 050-100) one o7e113) 51 Dementia 089 051-132) 80 081-120) 55 Datetas melts (0.99 090-108) 1105 095-147) a Haat serine usd in th baling year No.of ter prescription medications 0 173(136-190) oot 1196 1.72225) 1 125(113.139) ot si (14018) 2 096 086-107) at a0 (144149) 35 087 070008) 01 123 (110138), = 085 050.071) <0 1.00f Cutan physician encour (al aus) oy 1.16 (107-128) <0 s.00f NA 2 095 085-106) 30 (193 (050-105) 2 35 102 096-11) 50 ‘in3 093-118) 0 =6 084 077.002) <0 97 087-100), a1 Hospi (095 087-108) 24 oa3\o72-00) 03 Abbreviations: AH, antygeransiv; CABG coronary artery bypass ga CHD, coronary eat disease Cl, confidence tena LL, powering ‘Moca farcin WA not plicable PTCA, percutaneous tansurial coreatysngiopasy. 5 ato was adjusted for al att actors in he ble of 2 or more AH medications. A given day was assumed, to be covered if any drug for the indication of interest ‘was available. Such an approach is likely to be accurate for LL therapy, which in most patients consists of stat- ins alone, In contrast, multidrug therapy is common in the treatment of hypertension. The observed greater ad- herence with AH relative to LL medications may, thus, be parily a function of the measurement technique used. Second, this analysis assumes that all patients received, prescription medications only through their primary health insurance plan, There are several possible sce- narios under which medication tse might not be eap- tured by the plan (eg, physician-provided samples or claims submitted through other coverage), but these are unlikely to occur frequently among commercially in- sured patients with a pharmaceutical benefit. Third, lim lation of this study is that patient-level benefit struc- lures and changes were not available in the data, Health plans may have altered pharmacy benefits during the study, and increased co-payments or coverage eaps could lead to decreased persistence or adherence in the af- fected patients, Nevertheless, the results of this analysis have impor- tant implications for clinicians and other deciston mak- cers responsible for treating patients with comorbid hy- pertension and dyslipidemia, Long-term adherence wil ‘concomitant AH and LL therapy in managed care pa- tients was poor. This is extremely concerning given the high risk of cardiovascular events in patients with con- ccomitant hypertension and dyslipidemia" and the bet fits of treating these 2 risk factors optimally. The fac~ tors observed to predict adherence in this study, all of which are available to the physician at initiation of therap provide useful information about which patients are like to be poorly adherent with prescribed therapy and the potential means to improve the management of concomi- (©2003 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017tant hypertension and dyslipidemia. Clinicians should be aware of the factors likely to be associated with poor ad- hherence, such as time taking therapy, young age, female sex,and the absence of cardiovascular events, and should, larget interventions to increase compliance accord- ingly. For example, because of the sharp decline in ad- hherence in the first 6 months of concomitant therapy, in- terventions to promote adherence are more likely to have significant impact if initiated soon aller treatment be- fins. Inaddition, physicians may beable to improve medi- cation adherence substantially by reducing the number of concomitant medications and by initiating AH and LL, medications together of close in time. Any improve ment in adherence with concomitant AH and LL medi- cations is likely to be associated with substantial public health care benefits Accepted for Publication: December 7, 2004. ‘Correspondence: Richard H. Chapman, PhD, ValueMed- les Research, LLC, 300 N Washington St, Suite 303, Falls ‘Church, VA 22046 (rick.chapman@valuemedics com), Punding/Support: This study was supported by a grant from Pfizer Inc, New York, NY (ValueMedies Research, Lc), Previous Presentation: This study was presented as a poster at the American Heart Association's Seienifie Ses- sions, November 11, 2003, Orlando, Fla; and at the An- nual Meeting of the International Society for Pharma- coeconomics and Outcomes Research, May 18, 2004, Arlington, Va ‘Acknowledgment: We thank Dan Pettitt, DVM, MSe, for developing the initial concept and design of this study. —_ EES} 1. mais Hu esocton Hur Dis and Stoke Stats: 2004 Up Oat, Ter: Amaia Heat arian: 2003 2, Fgnns Ml Pipe Muro Use pi laveing dag fr rina se: ‘etn fcoray at dss metaaajss a andoisd as BL 200, ‘rrae-es 83. Russ 0, Alen Cony ta Ci oatonesin stat taten a: metas, Ah em Med 100188 170-1802 4 Mal, Mafaon 8, Chapman Mood Pressure Lovering Tear i ‘st Clabrton Eat a CE itor lum agai, ae ert esureloweng dus: ess of prospect degre veins oa hari ral Lane 2002561651064 5, Lawl, Wala Ruka AR Guang it of stats o ow drs Darrcan chleeral chemi haa dae. and Sole seems Sd tana 4G, 205 325:1028-106, 6 LawifR, Wald, Marie. Joan RE. Vai aw dos combination ast: ‘ment it lod pressurlomting drugs: nays of 34rd is. UL nce 27-8. 7 ALLA ie an Caos for te LAAT Coat esha jr comes incerta hypecolselchypeensie paersa- a a. (aepnoyteD) ARCHINTERN WEDIVOE 1, WAVER SOF ened to pravastatin ve wal arth Sothypartansie and Lp owing “rnment Proven Hen Atak Tl ALATLT) JA 200288208 7 Sear PS Dil Pouker NR el. Prvanton of ronan stoke ees wh terastatn in hypertensive patents who fave average or lover-ar ‘rage cles conaiaons, i the fag Sandia Care Os ‘ames T-Lpe Lowen rm ASQOTLLA2 mutant andoisedcon. ‘ole i. 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Copan with sanypriensi harap mong ei eres: resol ap, ge der, andre. Av Pe Hetty 105 5105-1208, Jang Zea SL. Longtusin daa using gnrizd near modes Bomecia. 186721222. Caro, Ses M, Span JL, apie, aceon D. Passtnc wh es ‘ent oryprnsion nacual prac. CAL 198.1609. Scare 18 MeLaupln, Gifs, Ald, Patt Adherence choc ‘harap among aliens ate rhein, lima, orb abstract, JA Cl Gael 20051 sup AS25A, Asta 19557 Hunk MS Godman, Toston Ae Te een in marty om ‘cranny han dense 1000100: of secular wens nik tars deinen. JAMA TOT. 27PSE6 5, ‘Wad, La tty o rede cars a. uu ns enro- a2, Wong NO, PoJR Fann S, Len Kamath TV, Villans GR Pre ing aan vey pil ent od pressures bpd pats wth th mabe syne Ae Cro! 2003 9:121-1426. aoe, Voda, Larsen, sen GV Paring HH Padersen Oita imerenion and aasur dase in patos with ype? dbs. Mn! ied 2003308 38-393 Disk Artec ty ofpsicunce yh ‘econeuretto-ilhpynpaente wth ype Aaupli2, Bona, Wogon Kick, Seymour AA. Gres reductions in AICin ype 2 diate pars new heap wh uridelnetorin bts as compared ‘to ghburdeco-aéministed with metomin. Diabetes Obs Met. 203; Banta Bank LiSale J Rates R, Per BA, Sun F.Amodpinatonasatin ile plu ea improves onal atainmert inh resent of oncom Ferensin ad dysipcenateGon su abst Am Cot Cue 20 ‘Soup AA Abst 100810, by more tan Jopilcambiatonteapy ton. Manag Cre 200 (©2005 American Medical Association, All rights reserved. ‘Downloaded From: http:/jamanetwork.com/pdfaccess.ashx?url=/data/journals/intemed/12030/ on 02/17/2017