effectiveness of dader method for pharmaceutical care on ... farmaceuti… · with cvd). secondary...

www.amcp.org Vol. 18, No. 4 May 2012 JMCP Journal of Managed Care Pharmacy 311

•Despite the availability of evidence-based guidelines for treat-ment and prevention of cardiovascular disease (CVD), manypatientsdonotachievetherapeuticgoals.InstudiesbyBanegasetal.(1998)andRodríguez-Rocaetal.(2005),only15.5%-33.5%ofpatientsreceivingdrugtherapyforhypertensionachievedtheirbloodpressure(BP)treatmentgoals.Similarly,Olsonetal.(2001)reported that only 21% (range 18%-35%) of patients receivinglipid-loweringtherapyachievedtheircholesteroltargets.

•Community pharmacists working in cooperation with patientsandotherhealthcareprofessionalscouldcontributetoachievingdesiredoutcomes inpatientswithchronicdiseases.Aprospec-tiverandomizedcontrolledtrial(RCT)byMorgadoetal.(2011),conductedinasecondarycarehypertension/dyslipidemiaoutpa-tientclinic, foundBPcontrol ratesof63.3%(62/98) inpatientsreceivingpharmaceuticalcare,comparedwith43.4%(40/99)intheusualcaregroup.AnRCTofpatientsathighcardiovascular(CV) riskbyTsuyukiet al. (2002) found theprimaryendpoint(performanceof a fasting cholesterol panel by thephysicianoradditionor increaseindoseofcholesterol-loweringmedication)was reached in 196 patients (57%) in a community pharmacyintervention group, compared with 102 (31%) in usual care.However, in a recent systematic review of studies evaluatingcommunitypharmacistinterventionsforpreventingormanagingdiabetes,CVD,and/ormajorCVriskfactors,Evansetal.(2011)concluded that there is aneed formorehigh-quality studiesoftheseinterventions.

What is already known about this subject

Effectiveness of Dader Method for Pharmaceutical Care on Control of Blood Pressure and Total Cholesterol in Outpatients

with Cardiovascular Disease or Cardiovascular Risk: EMDADER-CV Randomized Controlled Trial

Pedro Amariles, PhD, PharmD; Daniel Sabater-Hernández, PhD, PharmD; Emilio García-Jiménez, PhD, PharmD; Miguel Ángel Rodríguez-Chamorro, PhD, PharmD;

Rosa Prats-Más, PhD, PharmD; Francisco Marín-Magán, BSc, MSc; José Antonio Galán-Ceballos, BSc, MSc; José Jiménez-Martín, PhD, PharmD;

and María José Faus, PhD, PharmD

ABSTRACT

BACKGROUND: Although some studies have demonstrated that pharmacist intervention can improve drug therapy among patients with cardiovascular disease (CVD), more evidence derived from randomized controlled trials (RCTs) is needed, including assessment of the effect of community phar-macist interventions in patients with CVD.

OBJECTIVE: To assess the effectiveness of the Dader Method for pharma-ceutical care on achieving therapeutic goals for blood pressure (BP), total cholesterol (TC), and both BP and TC (BP/TC) in patients with CVD and/or high or intermediate cardiovascular (CV) risk attending community pharma-cies in Spain.

METHODS: Patients aged 25 to 74 years attending community pharma-cies with a prescription for at least 1 drug indicated for CVD or CV risk factors were randomized to 2 groups: an intervention group that received pharmaceutical care, which was provided by specially trained pharmacists working in collaboration with physicians, and a control group that received usual care (routine dispensing counseling) and verbal and written coun-seling regarding CVD prevention. Patients were recruited from December 2005 to September 2006, and both groups were followed for 8 months. Study outcomes were assessed at baseline and at 16 and 32 weeks after randomization. The primary outcome measures were the proportions of patients achieving BP, TC, and BP/TC therapeutic goals (BP lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for patients with diabetes, chronic kidney disease, or history of myocardial infarction or stroke; TC lower than 200 mg per dL for patients without CVD and lower than 175 mg per dL for patients with CVD). Secondary outcomes were mean BP and TC values. BP was assessed manually by the pharmacist after a 10-minute rest in the supine position. This measurement was performed twice for every participant, and the average of the 2 measurements was calculated. TC was measured by the pharmacist during the study visit using the enzymatic dry method. Statistical analyses were performed using 2-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; P < 0.05 was considered statisti-cally significant.

RESULTS: 714 patients were included in the study (356 intervention, 358 control), and the mean [SD] age was 62.8 [8.1] years. The 2 groups were similar at baseline in clinical and demographic characteristics, including the proportion of patients at therapeutic goals for BP, TC, and BP/TC. After 8 months of follow-up, there were statistically significant differences in favor of pharmaceutical care in the proportions of patients who achieved therapeutic goals for BP (52.5% vs. 43.0%, P = 0.017), TC (56.5% vs. 44.1%, P = 0.001), and BP/TC (37.1% vs. 21.8%, P <0.001).

RESEARCH

CONCLUSION: Compared with usual care plus written education, pharma-ceutical care focused on patient evaluation and follow-up in collaboration with physicians improved the achievement of BP, TC, and BP/TC treatment goals in patients with CVD and/or high or intermediate CV risk attending community pharmacies in Spain.

J Manag Care Pharm. 2012;18(4):311-23

Copyright © 2012, Academy of Managed Care Pharmacy. All rights reserved.

312 Journal of Managed Care Pharmacy JMCP May 2012 Vol. 18, No. 4 www.amcp.org

InSpain,itisestimatedthatonly10%ofpatientswithhighorveryhighcardiovascular(CV)riskhavemajorCVriskfac-tors,suchashypertension,hypercholesterolemia,diabetes,andsmoking, under control.10 Similarly, an analysis of NationalHealthandNutritionExaminationSurvey(NHANES)datathatassessed the prevalence, treatment, and control of combinedhypertension and hypercholesterolemia in the United Statesamongasampleof2,864adultsaged20yearsorolderfoundthat, among 638 adults, the percentage controlled for com-binedhypertensionandhypercholesterolemiawasonly9%.11 Accordingly,thereisaneedforexploringdifferentstrategiestoincreasethepercentageofpatientsachievingtherapeuticgoalsforCVriskfactors.

Communitypharmacists,incooperationwithpatientsandotherclinicians,couldmonitortherapeuticplansandcontrib-ute to the achievement of clinical outcomes in patientswithchronicdiseases.12Somestudieshaveshownthatpharmacistparticipation in designing, implementing, and monitoringtherapeuticprogramsinpatientswithCVDorCVriskfactorscould(a)improvethepatient’sknowledge,13(b)facilitateadop-tionofandoutcomesfromlifestyleinterventions,14(c)improvethe identification of candidates and the results of primary15 or secondary16prevention, and (d) increase thepercentageofpatients with high CV riskwho achieve the goals related toBP17-20 and lipid9,21 levels. Incontrast,other randomizedcon-trolled trials (RCTs) have found that community pharmacistinterventiondidnotleadtoimprovementsinprimaryoutcomemeasures (e.g., hospital admissions22 or the proportion ofpatientsreceivingappropriatemedication23).

Inasystematicreviewandassessmentofthequalityofstud-iesevaluatingcommunitypharmacistinterventionsinprevent-ingormanagingdiabetesorCVDand/ormajorCVriskfactors,Evansetal.(2011)foundthatstudyqualitywasgenerallypoor(poor design and/or poor reporting), most studies assessedonly biomarkers, and none of the studies demonstrated anybenefits in major health outcomes (e.g., hospital admissionsor mortality). They concluded that there is a need for morehigh-quality studies of community pharmacist interventionsinpatientswithCVD.24

Theobjectiveof thepresent studywas toassess theeffec-tivenessof theDaderMethod forpharmaceuticalcareon theachievementoftherapeuticgoalsforBP,totalcholesterol(TC),andbothBPandTC(BP/TC)inpatientswithCVDand/orhighor intermediateCV risk attending communitypharmacies inSpain. TCwas chosen as a therapeutic goalmeasure insteadof low-density lipoprotein cholesterol (LDL-C) because TCis measurable during community pharmacy visits, whereasLDL-Cisnot.

■■  MethodsDetailed methods of EMDADER-CV (Efecto del MétodoDáderdeSeguimientoFarmacoterapéuticoenelriesgocar-diovasculardepacientesconfactoresderiesgooenfermedad

Effectiveness of Dader Method for Pharmaceutical Care on Control of Blood Pressure and Total Cholesterol in Outpatients with Cardiovascular Disease or Cardiovascular Risk: EMDADER-CV Randomized Controlled Trial

•TheDaderMethodforpharmaceuticalcareincludespatientedu-cationaboutCVdrugs,completionofadrugtherapyprofileand/ordrughistory,assessmentofdrugcompliance,patientcounsel-ingaboutlifestylemodifications,pharmacist-performedinterven-tions not related to changes in drug therapy, and pharmacist-deliveredtreatmentrecommendationstophysicians.

•Toourknowledge,thereisalackoflargeRCTsdesignedtoevalu-atetheeffectofcommunitypharmacistinterventionsonachiev-ingtherapeuticgoals forBP, totalcholesterol(TC),andbothBPandTC(BP/TC)inpatientswithCVDorCVriskfactors.

What is already known about this subject (continued)

•The EMDADER-CV (Efecto del Método Dáder de SeguimientoFarmacoterapéuticoenelriesgocardiovasculardepacientesconfactores de riesgo o enfermedad cardiovascular [EffectivenessofDaderMethod for PharmaceuticalCare onControl of BloodPressureandTotalCholesterolinOutpatientswithCardiovascularDiseaseorCardiovascularRisk])studywasalargeRCTdesignedtoassesstheeffectoftheDaderMethodforpharmaceuticalcareon the achievementof therapeuticgoals forBP,TC, andBP/TCincommunitypharmacypatients(n=714)withCVDorCVriskfactors.

•After8monthsfollow-up,therewerestatisticallysignificantdif-ferences in favor of the intervention group (n=356) comparedwith the control group (n=358) in the percentage of patientswhoachievedtherapeuticgoalsforsystolicBP(54.5%vs.45.5%,oddsratio[OR]=1.43,95%CI=1.06-1.94);BP(52.5%vs.43.0%,OR=1.47,95%CI=1.08-1.99);TC(56.5%vs.44.1%,OR=1.64,95%CI=1.21-2.23);andBP/TC(37.1%vs.21.8%,OR=2.12,95%CI=1.50-2.98).

What this study adds

Cardiovascular disease (CVD) is the leading cause ofmortalityanddisabilityworldwide.1Itisconsideredanimportant public health problem because of its high

prevalence,mortality,andnegativeeffectsonhealthandqual-ity of life.2 Therefore, prevention and treatment of CVD areessential elementsof chronicdisease control.3Despite recentadvances, evidence of benefits obtained with treatment andpreventionofCVD,andtheavailabilityoftreatmentguidelinessupported by the results of clinical studies,4 there is a gapbetween evidence-based recommendations and routine clini-calpractice.5Asaconsequence,manypatientsdonotreceivenecessary therapeutic interventions or do not achieve theirtherapeutic goals.6 For instance, in studies by Banegas et al.(1998)andRodríguez-Rocaetal.(2005),only15.5%-33.5%ofpatientsreceivingdrugtherapyforhypertensionachievedtheirblood pressure (BP) treatment goals,7,8 rates similar to thoseof patients with hypercholesterolemia.6,9 Olson et al. (2001)reportedthatonly21%(range18%to35%)ofpatientsreceiv-inglipid-loweringtherapyachievedtheircholesteroltargets.6

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884446/pdf/bcp0057-0328.pdf

http://archinte.ama-assn.org/cgi/reprint/169/21/1996


http://www.bmj.com/highwire/filestream/366386/field_highwire_article_pdf/0.pdf

http://fampra.oxfordjournals.org/content/24/2/189.full.pdf+html

http://www.who.int/chp/chronic_disease_report/full_report.pdf

http://hyper.ahajournals.org/content/32/6/998.full.pdf+html

http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=13073917&pident_usuario=0&pcontactid=&pident_revista=255&ty=112&accion=L&origen=elsevier&web=www.revespcardiol.org&lan=en&fichero=255v58n04a13073917pdf001.pdf



cardiovascular[EffectivenessofDaderMethodforPharmaceuticalCare on Control of Blood Pressure and Total Cholesterol inOutpatients with Cardiovascular Disease or CardiovascularRisk]) have been published previously (in Spanish only).25 Overall, theEMDADER-CVwasanRCTdesigned tocomparetheeffectivenessof theDaderMethod forpharmaceuticalcarewiththatoftheusualcareprocess inacommunitypharmacysetting inSpain.Patients aged25 to74years andattending acommunity pharmacy with a prescription for at least 1 drugindicatedforCVDorCVriskfactorswererandomizedto1of2 groups: an intervention group that received pharmaceuticalcare,whichwasprovidedbyspeciallytrainedpharmacists,oracontrolgroupthatreceivedusualcare(routinedispensingandoralcounselingregardingdrugs)andverbalandwrittencoun-selingregardingCVdiseaseprevention(informationaboutCVDandCVriskfactors).Priortoallstudyvisits,describedindetailbelow,patientsinbothgroupsreceivedtelephonecallsfromthestudypharmacist,whoencouragedtheirattendanceatthevisits.

Community Pharmacist Recruitment Sixtycommunitypharmacistsfrom13provincesofSpainwereinvitedtoparticipateinthestudy:45weretakingthecertificateprogram inpharmaceutical care;10had taken thecertificateprograminpharmaceuticalcare;and5hadamaster’sdegreein pharmaceutical care from the University of Granada. Ofthese,allpharmacistswhoagreed toattendan informationalmeetingandtoparticipateinthestudywereprovidedwithan8-hour training course on pharmacist interventions inCVD.Thiscourse included lecturesonCVD,CVrisk factors,CVDprevention,and interventionandmonitoringofpatientswithriskfactorsorCVD,focusingontherapeuticgoalsforBPandTC,accordingtoeachpatient’sclinicalcondition.

Patient Recruitment and Group AssignmentResearchersrecruitedpatientswhometthefollowinginclusioncriteria:(a)aged25to74years;(b)presentedatthepharmacywithaprescriptionforatleast1drugindicatedforhyperten-sion,hypercholesterolemia,CVDprophylaxis,ortype2diabe-tes;and(c)hadahighormoderateCVriskaccording to theSystematicCoronaryRiskEvaluation (SCORE)systemand/ortheWilson-Grundymethod,adaptedforSpain.26ParticipantswereexcludedfromthestudyiftheyhadaBPof180/110mil-limeters mercury (mm Hg) or higher; history of myocardialinfarction in theprevious3months; a terminaldisease (e.g.,terminal cancer or chronic kidney disease on dialysis); anintellectual or physical disability that prevented them fromparticipating in the study;or if theywere currently includedinacardiacrehabilitationprogram.Patientswererandomizedto1of2groups,interventionorcontrol,andwerefollowedfor8months.An8-monthtimeframewaschosenbecauseitper-mittedcaptureofatleast3stablechangesinTCandBPvaluesassociatedwithdrugtherapyandlifestylemodifications.

RandomizationPatientswereassignedtotheinterventionorthecontrolgroupusingacomputer-generatedrandomizationschedule thatwasdesignedusingtheLinuxoperatingsystem,thecompilerGCCversion 3.3.5 (Debian 1:3.3.5-12; free software available atwww.debian.org), and the programming language C++. Theprogram generated a sequence of 1,000 random numberswithnorepetition(1to1,000)andassignedthecodeONEto500 numbers and the code ZERO to the other 500. Finally,it grouped theprevious1,000 randomnumbers (codedONEorZERO) into50groupsof20.Eachpharmacy entered intothestudywhenthepharmacistsubmittedbyfaxoremailtherecordof the firstpatientwho fulfilled the inclusioncriteria.Once the study’s coordinator verified the fulfillment of theinclusion criteria, he randomly assigned 1 of thementioned50 groups to the pharmacy, providing it with a sequence of20codes(ONEorZERO)thatdeterminedwhichpatientwasassignedtotheinterventiongrouporthecontrolgroup.

Intervention Group: The Dader Method for Pharmaceutical CareThe Dader Method for pharmaceutical care is a systematicprocess developed by the ResearchGroup of PharmaceuticalCare at theUniversity of Granada, Spain.27 The interventionis based on the use of pharmacotherapy records, evaluationof an assessment form that includes all CV health problemsand theCVdrugsused to treat thesemedicalproblems, andtheirassessmentonaspecificdate.Thisassessmentisusedtoidentify(a)anypotentialoractualpatienthealthoutcomesthatarenotconsistentwiththeobjectivesofpharmacotherapyandare associatedwith the use ofmedicines (negative outcomesassociatedwithmedication[NOM])and(b)situationsinwhichtheuseofmedicinescausedormaycausetheappearanceofanNOM(drug-relatedproblems[DRP]).28Oncetherelevantprob-lemsareidentified,thenecessaryinterventionstopatientsortophysiciansarecarriedouttosolvetheidentifiedNOMandarefollowedbyasubsequentassessmentoftheachievedoutcomes.

In the present study, pharmaceutical care was providedonaregularbasisaccordingtoasystematicanddocumentedmethod and carried out in collaboration with patients andphysicians(Figure1).28Thus,intheinterventiongroup,phar-macistsdidthefollowing:27 (a)ObtainedpatientdatarelatedtoCVmedicalproblemsand

current drug therapy. Patient-specific data were obtainedby interviewing the patient and reviewing the drug andclinicalrecords(mainlydrughistoryandresultsofclinicallaboratory tests that patients presented during the inter-view).

(b)Used the collecteddata to complete the assessment form,whichwasinterpretedandevaluatedonceallthenecessaryinformationwasadded.Thekeyelementtocompletingtheassessment form was the pairing of the health problems


http://farmacia.ugr.es/ars/pdf/416.pdf

http://scielo.isciii.es/pdf/pharmacy/v4n1/giaf.pdf

http://farmacia.ugr.es/ars/ars_web/ProjectARS/pdf/374.pdf





FIGURE 1 General Overview of EMDADER-CV

1. Patients presenting at the pharmacy with at least 1 prescription for a medication indicated for hypertension, hypercholesterolemia, cardiovascular prophylaxis, or type 2 diabetesa

2. Patient informed of study and asked to participate

Patient agreed to participate?

Patients excluded No

3. Assessed blood pressure, total cholesterol levels, and absolute cardiovascular risk

Yes

4. Patient with high or intermediate absolute cardiovascular risk and met other inclusion criteria?

No

Yes

5. Randomization by study coordinator Control: Usual care plus written education

Intervention: Dader Method for pharmaceutical care

6. Dispensing, verbal and written counseling regarding cardiovascular disease prevention (according to patient risk)b

6. Dispensing, verbal and written counseling regarding cardiovascular disease prevention (according to patient risk),b

and Dader method for pharmaceutical care

7. Week 0: Appointment for verbal and written counseling regarding cardiovascular disease prevention

(according to patient risk)c7. Week 0: Appointment for pharmaceutical care and verbal

and written counseling regarding cardiovascular disease prevention (according to patient risk)c

8. Week 16: Appointment for measurement of blood pressure and total cholesterol levels 8. Week 2-4: Appointment for pharmaceutical care and for

measurement of blood pressure and total cholesterol levels

9. Week 32: Final appointment for measurement of blood pressure and total cholesterol levels 9. Week 6-8: Appointment for pharmaceutical care and for

measurement of blood pressure and total cholesterol levels

10. Week 16-18: Appointment for pharmaceutical care and for measurement of blood pressure and total cholesterol levels

11. Week 32: Final appointment for pharmaceutical care and for measurement of blood pressure and total cholesterol levels

aExamples for hypertension included enalapril, amlodipine, valsartan, hydrochlorothiazide, bisoprolol, etc.; for hypercholesterolemia: atorvastatin, lovastatin, pravastatin, gemfibrozil, etc.; for cardiovascular prophylaxis: aspirin 100 mg, clopidogrel, etc.; for type 2 diabetes: glibenclamide, gliclazide, metformin, pioglitazone, rosiglitazone, etc. bA semivalidated cardiovascular disease knowledge questionnaire was applied to all patients in the visits that took place during weeks 0, 16, and 32. During the same visits, in 85 patients (41 control group and 44 intervention group), adherence to treatment was assessed using the Morisky-Green-Levine test.cDuring week 0, randomization took place.EMDADER-CV = Efecto del Método Dáder de Seguimiento Farmacoterapéutico en el riesgo cardiovascular de pacientes con factores de riesgo o enfermedad cardiovascular (Effectiveness of Dader Method for Pharmaceutical Care on Control of Blood Pressure and Total Cholesterol in Outpatients with Cardiovascular Disease or Cardiovascular Risk); mg=milligram.


with the current drug therapy, which provided a globalviewofthepatient’shealthstatusanditsrelationshipwiththedrugsused.

(c)Evaluatedthepatient’sdrugtherapyoutcomes.TheaimofthisstagewastoassesswhetherthedesiredtreatmentgoalsforBPandTCwereachieved.Forpatientswhosegoalswerenot yet achieved, the pharmacist developed therapeuticplansthatincludedinterventionswiththeaimofachievingthedesiredclinicaloutcome.

(d)ConductedaninterventionintendedtodirectlypreventorresolveanNOM.29Oncethepharmacistidentifiedconcernsabout themedicalproblemsandcurrentdrug therapy,heor she interpreted and analyzed this information in thecontextof the clinical condition illustratedby the assess-mentform,takingintoaccountfactorssuchasthepatient’sCVrisk,thetypeofCVprevention,andthemagnitudeofincreaseinBPorinTC.Iftheaimoftheinterventionwastomodifyaproblemwithlifestyleorwithuseofamedication,therecipientoftheinterventionwasthepatient.Iftheaimoftheinterventionwastomodifydrugtherapyineitheraquantitativeway (e.g.,modifying dosage or frequency) orqualitative way (e.g., adding or changing any drug), therecipientoftheinterventionwasthephysician.

(e) Completedanewassessmentform.Completionofaninter-vention should have generated a change in the patient’sassessment.DependingonwhetheranNOMstill existed,thetherapeuticplanwascarriedout.Examplesincluded(i)informingthephysicianthatdrugtherapyforhypertensionor forhypercholesterolemiawasnoteffectiveandthat thepatientthereforemayneedamodificationindrugtherapyand(ii)providingthephysicianwithinformationrelatedtoaneedfordrugtherapytoaddressmedicalproblemsorforCVDprophylaxis.

Patients assigned to the interventiongroupwereprovidedwithverbalandwrittencounselingregardingCVDprevention(accordingtopatientrisk).ToassesstheresultsofinterventionsonBPand/orTC,patientshadatleast5appointmentswiththepharmacistonweeks0(theweekduringwhichrandomizationtookplace),4-6,8-10,14-16,and32.BP,TC,bodymassindex(BMI), smoking status, and exercise routines were evaluatedduring those appointments. The timing of the intermediateappointments(weeks4-6,8-10,14-16)wasflexible,dependingontheamountoftimenecessarytoassesstheresultsofinter-ventionsthathadbeenperformed.

Control Group: Usual Care (Routine Dispensing), Verbal and Written Education Due to the nature of the intervention, participant blindingwasnotpossible.Therewasno“placebo”treatment,andafterrandomization,patientswere informedof theirgroupassign-ments.Thecontrolgroupreceivedtheusualcareprovidedbythepharmacist(routinedispensing,includingoralcounseling

regarding drugs) and written information and education onCVriskfactorsandCVD(Figure1).Thewrittenmaterialwasabrochuredesignedforthispurpose,30whichfocusedonthegoalsandimportanceofadherencewithpharmacologicalandnonpharmacological interventions toachieve treatmentgoals.Inaddition toavisitduringweek0 (theweekduringwhichrandomization tookplace),patientsmetagainwith thephar-macistonweeks16and32.Ateachappointment,BP,TC,BMI,smokingstatus,andexerciseroutineswereassessed.

In85patients(41fromthecontrolgroupand44fromtheinterventiongroup)adherencetotreatmentwasassessedusingthe Morisky-Green-Levine test on weeks 0, 16, and 32. Inaddition, a semivalidatedCVDknowledge questionnairewasappliedtoallpatientsatweeks0,16,and32.

Sample Size CalculationBased on the studies by Olson et al.,6 Banegas et al.,7 andRodríguez-Rocaetal.,8weassumedthat inthecontrolgrouponly30%ofpatientswould achieve thedesiredvaluesofBPand TC and that in the intervention group this percentagewould be 40%.With that difference inmind, a significancelevel of 0.05 (2-tailed) and a power of 80%,we estimated arequired sample size of 752patients (376 in each group).Toincreasestatisticalpowerforsecondaryoutcomes,wetriedtoachieveasamplesizeof1,000patients(500ineachgroup),20patientsfrom50pharmacies.

Outcome Data and AnalysisTheprimaryoutcomesweretheproportionsofpatientsachiev-ing BP, TC, and BP/TC therapeutic goals, according to theirclinicalconditions:BPlowerthan140/90mmHgforpatientswithuncomplicatedhypertension;lowerthan130/80mmHgforpatientswithdiabetes, chronickidneydisease, history ofmyocardialinfarction,orhistoryofstroke;andtotalcholesterollowerthan200milligramsperdeciliter(mgperdL)forpatientswithoutCVDandlowerthan175mgperdLforpatientswithCVD.4SecondaryoutcomesweremeanBPandTCvalues.

BPwasassessedmanuallybythepharmacistaftera10-min-uterestinasupineposition.Thismeasurementwasperformedtwiceforeveryparticipantateachvisit,andtheaverageofthe2measurementswascalculated.TCwasmeasuredbythephar-macistduring thevisitusing theenzymaticdrymethod.Forthispurpose,thepharmacistusedtheReflotronsystem(RocheDiagnostic, SL, Barcelona, Spain), standardized according tothe manufacturer’s instructions. At baseline and endpoint,control and intervention groups were compared in terms oftheproportionofpatientsat therapeuticgoal forBP,TC,andBP/TC.

Statistical Analysis. Statistical analyses were performedusingSPSSversion13.0(IBMSPSS,Armonk,NewYork).Datawere reported as means and standard deviations [SD] or as percentages. The Pearson chi-square test (between study


http://www.pharmacotherapy.org/avp/Pharm2707_Amariles-AVP.pdf

http://www.atencionfarmaceutica-ugr.es/index.php?option=com_remository&Itemid=62&func=startdown&id=34




■■  ResultsOfthe60communitypharmacists(from60pharmacies)invitedto participate in the study, only 40 (66.7%) participated inEMDADER-CV.ThefirstpatientwasrandomizedinDecember2005,andrandomizationwascompleted inSeptember2006.Follow-up was completed between August 2006 and June2007.The40participatingpharmacistsassessed993patientsforeligibility,but71patientsrefusedtoparticipate(Figure2).Fromtheremaining922patients,208didnotmeettheinclu-sioncriteria,and714subjectswereincludedandrandomized:356were assigned to the intervention group and 358 to thecontrolgroup.Themean[SD]ageofthepatientswas62.8[8.1]years,52.2%(373)weremales,and78.6%(561)hadhighCVrisk(Table1).Overall,the2groupsweresimilarinage,male-femaleratio,comorbidities,andotherclinicalconditions(allP values>0.05;Table1).

groups) and the McNemar test (within-group changes frombaselinetofollow-upat8months)wereusedtocomparepro-portions. The paired Student’s t-test (within-group changesfrom baseline to follow-up at 8months) or the independentsample Student’s t-test (between study groups) were used tocomparemeans;oddsratios(ORs)and95%confidenceinter-vals (CIs) were also estimated. Comparisons were analyzedusing 2-tailed tests, and P <0.05 was considered statisticallysignificant.

Ethical ApprovalEthical approval for the study protocol was granted by theUniversityofGranada’sHumanResearchEthicalCommittee,andvoluntarywritteninformedconsentwasrequiredfromallparticipants.


Lost to follow-upb

323 completed trial317 completed trial

Refused to participate

FIGURE 2 Flow of Patients Through the EMDADER-CV Study

Pool of 40 pharmacists assessed 993 patients for eligibility

922 patients eligible and agreed to participate

Patients refused to participate (n = 71)• 57:“lackoftime”• 14:“Idonotliketoparticipateinthiskindofstudy”

Did not meet inclusion criteria (n = 208)• 162assessedaslowcardiovascularrisk• 28agedmorethan74years• 10allocatedtocontrolgroup;however,pharmacistbelievedthat

patients needed intervention• 6withbloodpressuremorethan180/100mmHg• 1ondialysisandawaitingrenaltransplantation• 1fillingaprescriptionforanotherperson

Excluded by inclusion criteriaa

714 patients randomized

Intervention group (n = 356)Included in the intent-to-treat analyses (primary outcome measure)

Control group (n = 358)Included in the intent-to-treat analyses (primary outcome measure)

• 25failedtoattendthefirstscheduledappointment• 14movedoutofstudyarea

• 25failedtoattendthefirstscheduledappointment• 8movedoutofstudyarea• 2died

aNo exclusions were made for patients in a cardiac rehabilitation program, with intellectual or physical disability, or with history of myocardial infarction in the previous 3 months.bAnalyses assumed that all patients lost to follow-up from both the control and intervention groups did not achieve therapeutic goals for blood pressure or total cholesterol.EMDADER-CV = Efecto del Método Dáder de Seguimiento Farmacoterapéutico en el riesgo cardiovascular de pacientes con factores de riesgo o enfermedad cardiovascular (Effectiveness of Dader Method for Pharmaceutical Care on Control of Blood Pressure and Total Cholesterol in Outpatients with Cardiovascular Disease or Cardiovascular Risk); mm Hg = millimeters mercury.


therapeutic goals for BP, TC, andBP/TCwas similar in bothgroups in baseline demographics, comorbidities, and otherclinicalconditions.

After8monthsoffollow-up,theinterventiongroupshowedstatisticallysignificantincreasesinthepercentagesofpatientswho achieved therapeutic goals in SBP (18.3 percentagepoints, 95%CI=12.2-24.4); BP (19.6 percentage points, 95%CI=13.6-25.8);TC(14.1percentagepoints,95%CI=8.4-19.7);andBP/TC(23.3percentagepoints,95%CI=16.7-28.9;Table2). However, the increase in the proportion of patients whoachievedDBPtherapeuticgoalswasnotstatisticallysignificant(5.3percentagepoints,95%CI=–0.6-11.2).

Primary OutcomesAt baseline in the intervention group, 129 (36.2%), 236(66.3%), 117 (32.9%), 151 (42.4%), and 49 (13.8%) patientswere at their therapeutic goals for systolic blood pressure(SBP), diastolic blood pressure (DBP), BP, TC, and BP/TC,respectively(Table2).Thesepercentageswerenotsignificantlydifferent from the values in the control group, where 137(38.3%),242(67.6%),128(35.8%),140(39.1%),and51(14.2%)patientswereattheirtherapeuticgoalsforSBP(P =0.575),DBP(P =0.711),BP(P =0.417),TC(P =0.369),andBP/TC(P =0.853),respectively. The distribution of patients who achieved their


TABLE 1 Demographic and Clinical Characteristics Related to Primary Goal at Baseline

Demographic and Clinical VariablesTotal

(N = 714)Intervention Group

(n = 356)Control Group

(n = 358) P Valuea

Age,mean[SD] 62.8 [8.1] 63.0 [8.3] 62.6 [8.0] 0.506 % (n) % (n) % (n)

GenderMale 52.2 (373) 50.6 (180) 53.9 (193) 0.370Female 47.8 (341) 49.4 (176) 46.1 (165)

EducationElementaryschoolorless 70.9 (506) 71.4 (254) 70.4 (252) 0.767Highschool 15.8 (113) 14.9 (53) 16.8 (60)Universityeducation 13.3 (95) 13.8 (49) 12.8 (46)

Marital statusMarried 76.6 (547) 73.6 (262) 79.6 (285) 0.058Single 23.4 (167) 26.4 (94) 20.4 (73)

Self-reported health status Fair,poor,orverypoor 63.6 (454) 65.2 (232) 62.0 (222) 0.381Excellentorgood 36.4 (260) 34.8 (124) 38.0 (136)

Current smoker 20.3 (145) 19.1 (68) 21.5 (77) 0.424Current physical activity 52.9 (378) 54.8 (195) 51.1 (183) 0.328Body mass index (kg/m2)

Normal 14.1 (101) 14.1 (47) 16.1 (54) 0.665Overweight 37.4 (267) 38.8 (138) 36.0 (129)Obesity 40.8 (291) 41.9 (149) 42.5 (152)Mean[SD]b 30.0 [5.0] 29.9 [4.9] 30.1 [5.1] 0.589

Comorbid and other clinical conditions % (n) % (n) % (n)Secondaryprevention 28.6 (204) 29.8 (106) 27.4 (98) 0.478•Myocardialinfarction 11.2 (80) 11.8 (42) 10.6 (38) 0.616•Ischemicheartdisease 9.4 (67) 9.6 (34) 9.2 (33) 0.879•Cerebrovasculardisease 4.2 (30) 4.5 (16) 3.9 (14) 0.697•Peripheralarterialdisease 3.8 (27) 3.9 (14) 3.6 (13) 0.833

Diabetes 41.9 (299) 39.9 (142) 43.9 (157) 0.283Heartfailure 9.1 (65) 9.0 (32) 9.2 (33) 0.915Hypertension 86.7 (619) 88.8 (316) 84.6 (303) 0.104Dyslipidemia 71.3 (509) 71.3 (254) 71.2 (255) 0.972Familydyslipidemia 1.7 (12) 1.7 (6) 1.7 (6) 0.992Clinicalconditionthatindicateshighcardiovascularrisk 64.1 (458) 64.3 (229) 64.0 (229) 0.920Highcardiovascularrisk 78.6 (561) 77.8 (277) 79.3 (284) 0.621Mediumcardiovascularrisk 21.4 (153) 22.2 (79) 20.7 (74)

aTests of between-group differences for control versus intervention groups: Pearson chi-square test to compare proportions and the Student’s t-test to compare means.bn = 335 intervention, n = 334 control.kg = kilograms; m2 = squared meters; SD = standard deviation.


The control group also showed statistically significantincreases in the percentages of patientswho achieved thera-peuticgoalsinSBP(7.2percentagepoints,95%CI=1.6-12.9);BP(7.2percentagepoints,95%CI=1.7-12.8);andBP/TC(7.6percentage points, 95% CI=3.1-12.0; Table 2). However, theincreasesinthepercentageofpatientswhoachievedDBPther-apeuticgoals(2.8percentagepoints,95%CI=–2.5-8.1)andTCtherapeutic goals (5.0 percentage points, 95%CI=–0.2-12.0)werenotstatisticallysignificant.

Atthe8-monthfollow-up,therewerestatisticallysignificant

differences in favorof the interventiongroupcomparedwiththecontrolgroup in thepercentageofpatientsat therapeuticgoalsforSBP(9.0percentagepoints,OR=1.43,95%CI=1.06-1.94);BP(9.5percentagepoints,OR=1.47,95%CI=1.08-1.99);TC (12.3 percentage points, OR=1.64, 95% CI=1.21-2.23);andBP/TC(15.3percentagepoints,OR=2.12,95%CI=1.50-2.98;Table2,ORsnotshownintable).However,thebetween-groupdifferenceinthepercentageofpatientsatDBPtherapeu-ticgoalwasnotstatisticallysignificant(1.2percentagepoints,OR=1.06,95%CI=0.76-1.49).

TABLE 2 Changes in Primary and Secondary Outcomes

Primary OutcomesBaseline

% (n)8-Month Follow-Up

% (n)Difference (95% CI) P Valuea

Intervention group (n = 356 patients)Systolicbloodpressurecontrol 36.2 (129) 54.5 (194) 18.3 (12.2-24.4) < 0.001Diastolicbloodpressurecontrol 66.3 (236) 71.6 (255) 5.3 (–0.6-11.2) 0.076Bloodpressurecontrolb 32.9 (117) 52.5 (187) 19.6 (13.6-25.8) < 0.001Totalcholesterolcontrolc 42.4 (151) 56.5 (201) 14.1 (8.4-19.7) < 0.001Bloodpressureandtotalcholesterolcontrolb,c 13.8 (49) 37.1 (132) 23.3 (16.7-28.9) < 0.001

Control group (n = 358 patients)Systolicbloodpressurecontrol 38.3 (137) 45.5 (163) 7.2 (1.6-12.9) 0.012Diastolicbloodpressurecontrol 67.6 (242) 70.4 (252) 2.8 (–2.5-8.1) 0.303Bloodpressurecontrolb 35.8 (128) 43.0 (154) 7.2 (1.7-12.8) 0.011Totalcholesterolcontrolc 39.1 (140) 44.1 (158) 5.0 (–0.2-10.3) 0.060Bloodpressureandtotalcholesterolcontrolb,c 14.2 (51) 21.8 (78) 7.6 (3.1-12.0) 0.001

Between-group comparison at 8-month follow-up

Intervention Group % (n)

Control Group % (n)

Difference (95% CI)

P Valuea

Systolicbloodpressurecontrol 54.5 (194) 45.5 (163) 9.0 (1.6-16.3) 0.017Diastolicbloodpressurecontrol 71.6 (255) 70.4 (252) 1.2 (–5.4-7.9) 0.716Bloodpressurecontrolb 52.5 (187) 43.0 (154) 9.5 (2.2-16.8) 0.011Totalcholesterolcontrolc 56.5 (201) 44.1 (158) 12.3 (5.0-19.6) 0.001Bloodpressureandtotalcholesterolcontrolb,c 37.1 (132) 21.8 (78) 15.3 (8.7-21.9) < 0.001

Secondary Outcomes

Baseline Mean [SD]

8-Month Follow-Up Mean [SD]

Difference (95% CI)

P Valuea

Intervention group (n = 317)SystolicbloodpressuremmHg 145.5 [17.0] 134.2 [13.8] 11.3 (9.6-12.9) < 0.001 DiastolicbloodpressuremmHg 83.3 [10.4] 79.0 [8.6] 4.3 (3.2-5.4) < 0.001 TotalcholesterolmgperdL 197.8 [38.5] 180.3 [26.6] 17.5 (14.2-21.0) < 0.001

Control group (n = 323)SystolicbloodpressuremmHg 143.0 [17.6] 138.2 [15.7] 4.8 (3.1-6.5) < 0.001 DiastolicbloodpressuremmHg 82.0 [11.3] 80.1 [9.8] 1.9 (0.8-3.0) < 0.001 TotalcholesterolmgperdL 202.7 [40.8] 189.8 [30.9] 12.9 (9.6-16.1) < 0.001

Between-group comparison at 8-month follow-up

Intervention Group Mean [SD]

Control Group Mean [SD]

Difference (95% CI)

P Valuea

SystolicbloodpressuremmHg 134.2 [13.9] 138.2 [15.7] 4.0 (1.7-6.3) 0.001 DiastolicbloodpressuremmHg 79.0 [8.6] 80.1 [9.8] 1.1 (0.4-2.5) 0.158TotalcholesterolmgperdL 180.3 [26.6] 189.8 [30.9] 9.5 (5.1-14.0) < 0.001

aMcNemar test to compare proportions or Student’s t-test for paired samples to compare means for within-group changes from baseline to 8-month follow-up. Pearson chi-square test to compare proportions or the Student’s t-test for independent samples to assess differences in means between the control and intervention groups.bBlood pressure lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for those with diabetes, chronic kidney disease, or history of myocardial infarction or stroke.cCholesterol total lower than 200 mg per dL for patients without cardiovascular disease and lower than 175 mg per dL for patients with cardiovascular disease.CI = confidence interval; mg per dL = milligrams per deciliter; mm Hg = millimeters mercury; SD = standard deviation.



randomlyallocated to the intervention (n=98)or thecontrolgroups(n=99).17Attheendofthestudy,63.3%(62/98)ofthepatients receivingpharmaceutical care comparedwith43.4%(40/99) of control group patients reached the BP target (P =0.005); the intervention group also reached lowermean SBP(–6.8mmHg,P =0.006)andDBP(–2.9mmHg,P =0.020)thanthecontrolgroup(meansof134.2/82.5mmHgvs.141.0/85.4mmHg,respectively).ThesevaluesarehigherthanthoseintheEMDADER-CVstudy,inwhich52.5%ofpatientsintheinter-ventiongroupachievedBPgoalscomparedwith43.0%inthecontrolgroup(P =0.011),andinterventiongrouppatientshadalowerSBP(–4.0mmHg,P =0.001)butnotalowerDBP(–1.1mm Hg, P =0.158)thanthecontrolgroup(134.2/79.0mmHgvs. 138.2/80.1 mm Hg, respectively). Although these differ-encesmaybeattributedtothetype of practitioners(communitypharmacistsvs.hospitalclinicalpharmacists)andsetting(com-munitypharmacy vs. secondary care outpatient clinic in theuniversity hospital), amore likely explanation is that, in thestudybyMorgadoetal.,onlypatientsintheinterventiongroupwereprovidedwithwritteneducationalmaterialabouthyper-tensionandpossiblecomplications,aswellasinformationonhealthylifestylepractices.17Bycontrast,intheEMDADER-CVstudy,boththecontrolandtheinterventiongroupswerepro-videdwithwritteneducationalmaterialaboutCVriskfactorsandCVD andwere focused on goals and the importance ofadherence topharmacologicandnonpharmacologic interven-tionstoachievetherapeuticgoals.30WeconsiderthattobethereasonwhytheEMDADER-CVcontrolgroupshowedstatisti-cally significant increases in the percentage of patients whoachieved therapeutic goals forBP anddecreases in themeanvaluesofSBPandDBP.

In a 12-month, prospective, single-blind RCT by Hunt etal.(2008),designedtoevaluatetheeffectivenessofcollabora-tivemanagementofhypertensionbyprimarycare-pharmacistteamsincommunity-basedclinics,patientswithuncontrolledhypertension were randomized to a physician-pharmacistcollaborativemodel of care intervention (n=230) or tousualprimary care (n=233).18 According to an intention-to-treatanalysis in which chart review was used to obtain the lastrecordedbloodpressure values if thepatientmissed the lastclinic visit, this study reported that 54% (125/230) of thepatients in the intervention group achieved BP goals, com-paredwith42%(97/233)of thepatients in thecontrolgroup(P =0.005).Patients in the interventiongroupalsohad lowerSBP (–6mmHg, P =0.002) andDBP (–3mmHg, P =0.003)comparedwiththecontrolgroup(142/77mmHgvs.148/80mmHg).ThepercentageofpatientswhoachievedthetargetedBP in the study byHunt et al.was close to the value in theEMDADER-CV study; however, in the latter study, the inter-ventionandthecontrolgroupswerenotsignificantlydifferentintermsofDBP.Theinterventioninthephysician-pharmacistcollaborative model of care was similar to the interventionin the EMDADER-CV (the pharmacists reviewed subjects’

Secondary Outcomes Thebaselinemean[SD]valuesofSBP,DBP,andTCintheinter-ventiongroupwere145.5[17.0]mmHg,83.3[10.4]mmHg,and197.8[38.5]mgperdL,respectively.Thesevalueswerenotsignificantlydifferent fromthoseof thecontrolgroup,wherebaselinevaluesofSBP,DBP,andTCwere143.0[17.6]mmHg,82.0[11.3]mmHg,and202.7[40.8]mgperdL,respectively(Table2).

After 8 months of follow-up, patients in the interventiongroupshowedstatistically significantmean[SD]decreases inSBP(–11.3[14.8]mmHg),DBP(–4.3[9.8]mmHg),andTC(–17.5 [30.9]mg per dL; Table 2 [SDs not shown in table]).Similarly,patientsinthecontrolgroupshowedstatisticallysig-nificantdecreasesinthemeanvaluesofSBP(–4.8[15.4]mmHg),DBP (–1.9 [10.0]mmHg),andTC(–12.9 [29.8]mgperdL).Atthe8-monthfollow-up,therewerestatisticallysignifi-cantdifferencesinmean[SD]—SBP(–4.0[14.8]mmHg)andTC(–9.5[28.9]mgperdL)—infavoroftheinterventiongroupcomparedwiththecontrolgroup.ThedifferenceinmeanDBPwasnotstatisticallysignificant(–1.1[9.2]mmHg).

■■  DiscussionThe EMDADER-CV studywas a large (n=714 patients) RCTdesignedtoassesstheeffectoftheDaderMethodforpharma-ceuticalcareonachievingtherapeuticgoalsforBP,TC,andBP/TC in community pharmacy patientswithCVD and/or highor intermediateCV risk.Comparedwith usual care (routinedispensingandoralcounseling)pluswritteneducationalmate-rialaboutCVriskfactorsandCVD,pharmaceuticalcarepro-ducedsignificant improvements in thepercentageofpatientswho achieved therapeutic goals for BP, TC, and BP/TC. It isimportant to point out that the Dader Method incorporatedacombinationofstrategiesthatareconsideredkeytoachiev-ingbettercontrolofCVrisk,suchaspatienteducationonCVdrugs, completionof adrug therapyprofile and/ordrughis-tory,assessmentofdrugcompliance,patientcounselingaboutlifestylemodification,pharmacist-performedinterventionsnotrelated tochanges indrug therapy,andpharmacist-deliveredtreatmentrecommendationstophysicians.27,31

Toourknowledge, there isa lackof largerandomizedtri-als designed to evaluate the effect of community pharmacistinterventions in the achievement of therapeutic goals for BP,TC,andBP/TCinpatientswithCVDorCVriskfactors,whichwasthemainobjectiveoftheEMDADER-CVstudy.However,some studies, including some systematic reviews and meta-analysis,31-35 have demonstrated that pharmacist interventioncould improve theoutcomesofdrug therapy amongpatientswithhypertension17,18,21anddyslipidemia.9

A prospective RCT byMorgado et al. (2011), designed toevaluate if a pharmaceutical care program (quarterly follow-upbyahospitalpharmacistduringa9-monthperiod)couldimproveBPcontrol,evaluatedatotalof197patients,whowere



http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596500/pdf/11606_2008_Article_791.pdf







notexperienceasignificantreductioninthemeanvalueofDBP(–2.4mmHg [95%CI=–6.1 to 1.3] and –4.9 [3.0)]mmHg[P =0.103],respectively),whileinthepresentstudy,thecontrolgrouppatientsexperiencedasignificantdecreaseinthemeanvalueofDBP.Inadditiontodifferencesintermsofthetypeofstudies(meta-analysisvs.only1RCT),itisimportanttopointout that both the control and the intervention groups in theEMDADER-CVstudywereprovidedwithwritteneducationalmaterialaboutCVriskfactors.30

In a recent systematic review and meta-analysis of 30RCTs (11,765 patients) by Santschi et al. (2011), conductedto determine the impact of pharmacist care on themanage-ment of CV risk factors among outpatients, pharmacist carewas associatedwith significant reductions inmean values ofSBPandDBP(–8.1mmHg,95%CI=–10.2 to–5.9and–3.8mmHg, 95%CI=–5.3 to –2.3, respectively).34 These resultsareconsiderablyhigher than thereductionsobtained inbothSBPandDBPintheEMADER-CVstudyandinthesystematicreviews conducted byMachado et al.32 andMorgado et al.33

DifferencesobtainedinthesystematicreviewsbyMachadoetal.,32Morgadoetal.,33andSantschietal.34mightbeshowingatendencytoanoverall incrementintreatmentadherenceinthemostrecentstudies,whichhavetendedtofavorpharmacistcare comparedwith usual care and includedmore interven-tions involving physician-pharmacist collaboration33 and asubstantial heterogeneity.34 Despite these quantitative differ-ences, all these studies, includingEMDADER-CV, found thatcommunitypharmacy interventions improve theoutcomesofdrugtherapyamongpatientswithhypertension.17,18,31-34

In the Study of Cardiovascular Risk Intervention byPharmacists (SCRIP), an RCT of a community pharmacistintervention in primary care of patients with dyslipidemia,Tsuyukietal.(2002)assigned675patientswithCVDordia-beteswithotherCVriskfactors toapharmacist interventionincluding education and a brochure about CV risk factors;point-of-carecholesterolmeasurement;referraltotheirphysi-cians;regularfollow-upfor16weeks;andriskfactorinforma-tionprovidedbythepharmacisttothephysician,ortousualcare including the brochure, general advice, and minimalfollow-up.9 The primary endpoint (performance of a fastingcholesterol panel by the physician or addition or increase indose of cholesterol-loweringmedication)was reached in 196patients(57%) inthe interventiongroup,comparedwith102(31%)intheusualcaregroup.Althoughtheprimaryendpointin theSCRIPwasdifferent than thegoals established forTCintheEMDADER-CVstudy,thepercentageofpatientsintheinterventiongroupwhoreachedtheprimaryendpointintheSCRIPwassimilar to thepercentageofpatientswhoreachedtherapeuticgoalsforTCinourstudy.9

The reduction in TC obtained in the intervention groupof the EMDADER-CV study is considerably lower than the

medicationsandlifestylehabits,assessedvitalsigns,screenedfor adverse drug reactions, identified barriers to treatmentadherence, provided education, and scheduled follow-up appointments as deemed necessary). However, in theEMDADER-CV,pharmacistsdidnotmakedirectalterationstodrugregimenstotitratedosages,addanewagent,orswitchamedication;instead,theysentwrittenrecommendationstothephysician.Bycontrast,thephysician-pharmacistcollaborativearrangementstudiedbyHuntetal.permittedpharmacists tomakedrugregimenchangesdirectly.18

AsystematicreviewbyCarteretal.(2009),includingquasi-randomizedtrials,controlledbefore-afterstudies, interruptedtime-series studies, patient-randomized trials, and cluster-randomized trials anddesigned to assess the effectiveness ofinterventionsforBPinvolvingnursesorpharmacists,showedthatpharmacists’interventionswereassociatedwithasignifi-cantreductioninthemeanvalueofSBPwhenthepharmacistmadetreatmentrecommendationstothephysician(−9.30mmHg)orwhenthepharmacistperformedtheintervention(−8.44mmHg).31 In a nonparametric analysis of 13 studies involv-ingcommunitypharmacists,themean[SD]reductionsinSBPandDBPwere–9.31[5.00]and–4.59[4.64]mmHg.31Thesevaluesareclose to theresultsof theEMDADER-CVstudy, inwhich the intervention group experiencedmean [SD] reduc-tions inSBPandDBPof–11.3 [14.8]and–4.3 [9.8]mmHg,respectively. Additionally, based on the results of 5 studiesconducted in communitypharmacies,Carter et al. estimatedanORforcontrolledBPof2.89(95%CI=1.83-4.55)forcom-munitypharmacists,avaluehigherthantheORforcontrolledBPinourstudy(1.47,95%CI=1.08-1.99).However,Carteretal. clarified that if 2 studieswere excluded (1 because of anextremelyhighOR=29.7andtheotherbecausethepharmacistworkedcloselywith2physiciansandreviewedmedicalrecordsofstudyparticipantsinthephysicians’office,OR=4.29),and1additionalstudywasincluded(classifiedasanursinginterven-tionfortheORcalculations,buttheinterventioninvolvedbothanurseandacommunitypharmacist,OR=1.79),theestimatedORforcontrolledBPwouldhavebeen1.8,31avaluethatwouldbeclosertotheORobtainedintheEMDADER-CVstudy(1.47).

In the EMDADER-CV study, the difference in mean SBPin favorof the interventiongroupcomparedwith thecontrolgroupwas lower than that of –6.9 [12.0]mmHg (P =0.047)foundinthesystematicreviewbyMachadoetal.(2007)32butwasclosetothevalueof–4.9[0.9]mmHg(P <0.001)obtainedinthesystematicreviewbyMorgadoetal.(2011).33Bycontrast,neither theEMDADER-CVstudynor the reviewbyMachadoetal.32 foundsignificantdifferencesbetween the interventiongroup and the control group in DBP, whereas the differenceof –2.6 [0.9]mmHg (P <0.001)was significant in themeta-analysisbyMorgadoetal.33Inthemeta-analysesbyMachadoetal.32andbyMorgadoetal.,33thecontrolgrouppatientsdid












size was estimated assuming that in the control group only30%ofthepatientswouldachievetherapeuticgoalsforBPandTC.ThisassumptionwasmadebasedonindividualvaluesofBPandTCcontrolreportedinpreviouswork.6-9However,dur-ingtheprogressoftheEMDADER-CVstudy,somepublishedstudieswithdetailedinformationfromSpainshowedthatthepercentageofpatientswhoachievedtherapeuticgoalsforbothBPandTCwaslessthan20%.36Thus,ifweassumedthatintheintervention group this percentage would be improved from20% to 30%,with a significance level of 0.05 (2-tailed) andapowerof80%,wewouldestimatearequiredsampleof626patients(313ineachgroup).Asaconsequence,afinalsamplesizeof714patients(356intheinterventiongroupand358inthecontrolgroup)wouldbeconsideredasappropriateforthehypothesis and the primary outcomes of the EMDADER-CVstudy.

Finally, the EMDADER-CV studywas performed by care-fullyselectedcommunitypharmacists,whowere trainedandspecialized in pharmacotherapy follow-up and in using theDaderMethod,which limits thedegree towhich thepresentstudyfindingscanbegeneralizedtoothersettings.

■■  Conclusions Compared with usual care plus written education, pharma-ceutical care focused on patient evaluation and follow-up incollaboration with physicians improved the achievement ofBP,TC,andBP/TCtreatmentgoalsinpatientswithCVDand/or high or intermediate CV risk in a community pharmacysetting in Spain. The EMDADER-CV study demonstrates theaddedvalueofpharmaceuticalcarebycommunitypharmacistsinoutpatientswithCVDand/orhighorintermediateCVrisk.

reduction found in thepharmacist intervention group in thesystematic review andmeta-analysis in hyperlipidemiaman-agement by Machado et al. (2008),35 a mean [SD] of –34.2[10.3]mgperdL (P <0.001),which includeda totalof2,084patients(685inthepharmacistinterventiongroupand1,399in the control group). Although the significant reduction inTCobtainedinthecontrolgroupoftheEMDADER-CVstudyissimilartothenonsignificantreductioninthecontrolgroupofthereviewbyMachadoetal.,35amean[SD]of–13.7(10.3)mgperdL(P =0.186), themeandifferencebetween interven-tion and control groups in the present study is considerablysmallerthantheonereportedbyMachadoetal.,35–22.0(10.4)mgperdL(P =0.034).InthesystematicreviewbySantschietal.34basedon9studies(1,121patients),pharmacistcarewasassociatedwithasignificantreductioninTC,ameanof–17.4mg/dL(95%CI=–25.5to–9.2); thoseresultsareclosetothereductionfoundbyMachadoetal.35buthigherthanthevaluefound in the present study.Despite some quantitative differ-ences,evidencesuggeststhatcommunitypharmacistinterven-tionisbeneficialforpatientswithCVDorCVriskfactors.9,34,35

LimitationsFirst, theresultsmighthavebeensubjectedtopotentialbias.Because therewasno “placebo” treatment, the studypatientswere not blinded to treatment assignment, and both groups(interventionandcontrol)wereseenbythesamecommunitypharmacist, who was responsible for collecting BP and TCmeasurements.However,potentialbiaswasreducedbyphar-macistuseofastandardizedprocessforcollectingBPandTCmeasurementsinboththeinterventionandcontrolgroups.

Second, control group patients received telephone callsfromthepharmacist,whoencouragedtheirattendanceattheappointments.Controlgrouppatientswerealsoprovidedwithwritten and oral education about CV risk factors and CVDandwerecounseledongoalsandtheimportanceofadherenceto pharmacological and nonpharmacological interventions toachievetherapeuticgoals,asrequestedbytheHumanResearchEthicalCommitteeinitsapprovalofthisresearchproject.Thecommittee also requested that pharmacists provide patientswith the results of BP and TC assessments. In addition, allpatients were questioned about knowledge of CVD, and 41werequestionedabouttreatmentadherence.Therefore,controlgroup patients received some intervention, and 10 patientsallocatedtotheecontrolwereexcludedfromthestudybecausepharmacistsdeterminedthatthepatientsneededintervention.Theeffectofwritteneducationalmaterialandtheextraatten-tionreceivedbythepatientsintheusualcaregroupmighthaveproducedpositiveoutcomesandreducedthemagnitudeofdif-ferencescomparedwiththeinterventiongroup.

Thethirdpotentiallimitationwasthefinalsamplesize(714patients),whichwassmallerthanexpected(752patients).The

PEDRO AMARILES, PhD, PharmD, is Professor, University of Antioquia, Medellin, Antioquia, Colombia. DANIEL SABATER-HERNÁNDEZ, PhD, PharmD, is Research Associate; and EMILIO GARCÍA-JIMÉNEZ, PhD, PharmD, is Research Associate, Pharmaceutical Care Research Group, University of Granada, Granada, Spain. JOSÉ JIMÉNEZ-MARTÍN, PhD, PharmD, is Professor; and MARÍA JOSÉ FAUS, PhD, PharmD, is Professor, University of Granada, Granada, Spain. MIGUEL ÁNGEL RODRÍGUEZ-CHAMORRO, PhD, PharmD, is a community phar-macist, Talavera de la Reina, Toledo, Spain. ROSA PRATS-MÁS, PhD, PharmD, is a community pharmacist, Denia, Alicante, Spain. FRANCISCO MARÍN-MAGÁN, BSc, MSc, and JOSÉ ANTONIO GALÁN-CEBALLOS, BSc, MSc, are community pharmacists, Cádiz, Spain.

AUTHOR CORRESPONDENCE: Pedro Amariles, PhD, PharmD, University of Antioquia, Pharmacy, AA1226 Medellin-Colombia, Medellin, Antioquia 1226, Colombia. Tel.: 574.2195460; E-mail: [email protected].

Authors




mailto:pamaris%40farmacia.udea.edu.co?subject=


7.BanegasJR,Rodríguez-ArtalejoF,delaCruzTrocaJJ,Guallar-CastillónP,delReyCaleroJ.BloodpressureinSpain:distribution,awareness,control,andbenefitsofareductioninaveragepressure.Hypertension. 1998;32(6):998-1002.Availableat:http://hyper.ahajournals.org/con-tent/32/6/998.full.pdf+html.AccessedApril9,2012.

8.Rodríguez-RocaGC,Artigao-RódenasLM,Llisterri-CaroJL,etal.ControlofhypertensioninelderlypatientsreceivingprimarycareinSpain.Rev Esp Cardiol.2005;58(4):359-66.Availableat:http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=13073917&pident_usuario=0&pcontactid=&pident_revista=255&ty=112&accion=L&origen=elsevier&web=www.revespcardiol.org&lan=en&fichero=255v58n04a13073917pdf001.pdf.AccessedApril9,2012.

9.TsuyukiRT,JohnsonJA,TeoKK,etal.Arandomizedtrialoftheeffectofcommunitypharmacistinterventiononcholesterolriskmanagement:theStudyofCardiovascularRiskInterventionbyPharmacists(SCRIP).Arch Intern Med.2002;162(10):1149-55.Availableat:http://archinte.ama-assn.org/cgi/reprint/162/10/1149.AccessedApril9,2012.

10.DelaPeña-FenándezA,Saurez-FernándezC,Cuende-MeleroI,etal.[Integralcontrolofriskfactorsinpatientsofhighandveryhighcardiovas-cularriskinSpain.CIFARCproject.]Med Clin (Barc).2005;124(2):44-49.[inSpanish]

11.WongND,LopezV,TangS,WilliamsGR.Prevalence,treatment,andcontrolofcombinedhypertensionandhypercholesterolemiaintheUnitedStates. Am J Cardiol.2006;98(2):204-08.

12.InternationalPharmaceuticalFederation(FIP).FIPstatementofpolicy.Theroleofthepharmacistinthepreventionandtreatmentofchronicdis-ease.FIPCouncil,Brazil,August2006.Availableat:http://www.fip.org/www/uploads/database_file.php?id=274&table_id=.AccessedApril9,2012.

13.LalondeL,O´ConnorAM,DrakeE,DuguayP,LowensteynI,GroverSA.Developmentandpreliminarytestingofapatientdecisionaidtoassistpharmaceuticalcareinthepreventionofcardiovasculardisease.Pharmacotherapy.2004;24(7):909-22.

14.SimpsonDR,DixonBG,BolliP;HealthyHeartProgram.Effectivenessofmultidisciplinarypatientcounsellinginreducingcardiovasculardiseaseriskfactorsthroughnonpharmacologicalintervention:resultsfromHealthyHeartProgram.Can J Cardiol.2004;20(2):177-86.

15.AtthobariJ,MonsterTB,deJongPE,deJong-vandenBergLT;PrevendStudyGroup.Theeffectofhypertensionandhypercholesterolemiascreeningwithsubsequentinterventionletterontheuseofbloodpressureandlipidloweringdrugs.Br J Clin Pharmacol.2004;57(3):328-36.Availableat:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884446/pdf/bcp0057-0328.pdf.AccessedApril9,2012.

16.ChinwongS,ReidF,McGlynnS,HudsonS,FlapanA.Theneedforpharmaceuticalcareinthepreventionofcoronaryheartdisease:anexploratorystudyinacutemyocardialinfarctionpatients.Pharm World Sci. 2004;26(2):96-101.

17.MorgadoM,RoloS,Castelo-BrancoM.Pharmacistinterventionprogramtoenhancehypertensioncontrol:arandomisedcontrolledtrial.Int J Clin Pharm.2011;33(1):132-40.

18.HuntJS,SiemienczukJ,PapeG,etal.Arandomizedcontrolledtrialofteam-basedcare:impactofphysician-pharmacistcollaborationonuncon-trolledhypertension.J Gen Intern Med.2008;23(12):1966-72.Availableat:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596500/pdf/11606_2008_Article_791.pdf.AccessedApril9,2012.

19.WeberCA,ErnstME,SezateGS,ZhengS,CarterBL.Pharmacist-physiciancomanagementofhypertensionandreductionin24-hourambu-latorybloodpressures.Arch Intern Med.2010;170(18):1634-39.Availableat:http://archinte.ama-assn.org/cgi/reprint/170/18/1634.AccessedApril9,2012.

20.CarterBL,ArderyG,DawsonJD,etal.Physicianandpharma-cistcollaborationtoimprovebloodpressurecontrol.Arch Intern Med. 2009;169(21):1996-2002.Availableat:http://archinte.ama-assn.org/cgi/reprint/169/21/1996.AccessedApril9,2012.

ACkNOwlEDGEMENTS

The authors would like to thank the Pharmaceutical Care Center of StadaLaboratories (Granada, Spain) for technical and logistical support in thecoordinationof theEMDADER-CVstudy, andProfessorAlejandroEstrada-Restrepo,NutritionandDieteticsSchool,UniversityofAntioquia,Medellin,Antioquia,Colombia,forhisstatisticalsupport.TheauthorswouldalsoliketothanktheEMDADER-CVcommunitypharmacists:AlejandroGómez-Ulla(SantiagodeCompostela),Milagros Jaime (Bolaños-CiudadReal),CayetanoChazarra (Orihuela-Alicante),ConcepciónMiler (Cádiz), InésRoig-Sánchez(Denia-Alicante), María Paz-Ros (Murcia), Amparo Gadea (Ciudad Real),Inmaculada Costas (Els Poblets-Alicante), María Elena Salvador (Gata-Alicante),AnaLillo(Lliber-Alicante),TeresaRóspide(CiudadReal),AlfonsoRodríguez-Chamorro(Alcañizo-Toledo),FélixGarcía-Lozano(CiudadReal),Carmen Álvarez (Cádiz), Francisca Cobo-Castro (Ciudad Real), RosarioPilar Fernández Jaldón (Cádiz), RocíoMateos (Ciudad Real), Pilar Cordón(Lucena-Córdoba), María Ángeles Ramírez (Cádiz), Marian Beidas Soler(Ibiza),AntonioGasent(Alicante),CintaGalván(Huelva),MaríaPilarÁlvarez(Piedrabuena-CiudadReal),MaríaEncarnaRaya(Jodar-Jaén),PalomaCortijo(Santander), Carmen Hervás (Ciudad Real), Ana Monzón (Cádiz), MaríaIsabel Roselló (Denia-Alicante), María Teresa Rodríguez (Elche-Alicante),Dora Sivera-Signes (Denia-Alicante), Ana María Díaz (Lorca), AlfonsoGómez-Caminero (Jaén),AnaSáez-Benito (Zaragoza),MaríaEcheveste (SanSebastián), Ana María Zaragoza (Denia-Alicante), Olaia Erauncetamurguil(SanSebastián).

DISClOSURES

This research was financed in part by Roche Diagnostics, SL, Spain, andStadaLaboratory,SL,Spain.EmilioGarcía-JiménezworksasPharmaceuticalCareAdvisor forStadaLaboratory.Theotherauthorsdeclarednopotentialconflictsofinterestwithrespecttotheauthorshipand/orpublicationofthisarticle.

Concept and design were performed by Amariles and Faus with theassistanceofSabater-Hernández,García-Jiménez,andJiménez-Martín.DatawerecollectedbyGalán-Ceballos,Marín-Magán,Prats-Más,andRodríguez-Chamorro.DatawereinterpretedprimarilybyAmariles,Sabater-Hernández,Faus, García-Jiménez, and Jiménez-Martín. The manuscript was writ-ten primarily by Amariles, Sabater-Hernández, Faus, García-Jiménez, andJiménez-MartínandwasrevisedprimarilybyGarcía-Jiménez,Jiménez-Martín,Amariles,Sabater-Hernández,andFaus.

REFERENCES

1.WorldHealthOrganization.Preventingchronicdiseases:avitalinvest-ment.WHOglobalreport.2005.Availableat:http://www.who.int/chp/chronic_disease_report/full_report.pdf.AccessedApril9,2012.

2.BeagleholeR,YachD.Globalisationandthepreventionandcontrolofnon-communicabledisease:theneglectedchronicdiseasesofadults.Lancet. 2003;362(9387):903-08.

3.ChoiBC,CorberSJ,McQueenDV,etal.EnhancingregionalcapacityinchronicdiseasesurveillanceintheAmericas.Rev Panam Salud Publica. 2005;17(2):130-41.

4.GrahamI,AtarD,Borch-JohnsenK,etal;ESCCommitteeforPracticeGuidelines.Europeanguidelinesoncardiovasculardiseasepreventioninclinicalpractice:executivesummary.Atherosclerosis.2007;194(1):1-45.

5.BrotonsC,MaiquesA,MostazaJ,PintoX,VilasecaJ;EstudioEMOSCOL.[Lipidcontrolinsecondaryprevention:multicenterobservationalstudyinprimarycare.]Aten Primaria.2004;34(2):81-86.[inSpanish]

6.OlsonKL,BungardTJ,TsuyukiRT.Cholesterolriskmanagement:asys-tematicexaminationofthegapfromevidencetopractice.Pharmacotherapy. 2001;21(7):807-17.





















29.FausMJ,Sabater-HernándezD,AmarilesP.Typesofpharmacistinter-ventionsintendedtopreventandsolvenegativeoutcomesassociatedwithmedication[e-letter].Pharmacotherapy.2007;27:e51-e52.Availableat:http://www.pharmacotherapy.org/avp/Pharm2707_Amariles-AVP.pdf.AccessedApril9,2012.

30.Sabater-HernándezD,Amariles-MuñozP,García-CorpasJP,FausMJ.Howtoimproveyourcardiovascularhealth.GrupodeInvestigaciónenAtenciónFarmaćeutica(CTS-131).UniversidaddeGranada.2005.Availableat:http://www.atencionfarmaceutica-ugr.es/index.php?option=com_remository&Itemid=62&func=startdown&id=34.AccessedApril9,2012.

31.CarterBL,RogersM,DalyJ,ZhengS,JamesPA.Thepotencyofteam-basedcareinterventionsforhypertension:ameta-analysis.Arch Intern Med.2009;169(19):1748-55.Availableat:http://archinte.ama-assn.org/cgi/reprint/169/19/1748.AccessedApril9,2012.

32.MachadoM,BajcarJ,GuzzoGC,EinarsonTR.Sensitivityofpatientout-comestopharmacistinterventions.PartII:systematicreviewandmeta-anal-ysisinhypertensionmanagement.Ann Pharmacother.2007;41(11):1770-81.

33.MorgadoMP,MorgadoSR,MendesLC,PereiraLJ,Castelo-BrancoM.Pharmacistinterventionstoenhancebloodpressurecontrolandadherencetoantihypertensivetherapy:reviewandmeta-analysis. Am J Health Syst Pharm.2011;68(3):241-53.

34.SantschiV,ChioleroA,BurnandB,ColosimoAL,ParadisG.Impactofpharmacistcareinthemanagementofcardiovasculardiseaseriskfactors:asystematicreviewandmeta-analysisofrandomizedtrials.Arch Intern Med. 2011;171(16):1441-53.

35.MachadoM,NassorN,BajcarJM,GuzzoGC,EinarsonTR.Sensitivityofpatientoutcomestopharmacistinterventions.PartIII:systematicreviewandmeta-analysisinhyperlipidemiamanagement.Ann Pharmacother. 2008;42(9):1195-207.

36.BarriosAlonsoV,EscobarCervantesC,CalderónMonteroA,LlisterriCaroJL,EcharriCarrilloR,MatalíA.[Impactofthepresenceofcardiovas-culardiseaseonbloodpressureandlipidcontrolinthehypertensepopula-tionattendedinprimarycare.]Aten Primaria.2008;40(1):21-27.[inSpanish]

21.YamadaC,JohnsonJA,RobertsonP,PearsonG,TsuyukiRT.Long-termimpactofacommunitypharmacistinterventiononcholesterollevelsinpatientsathighriskforcardiovascularevents:extendedfollow-upofthesecondStudyofCardiovascularRiskInterventionbyPharmacists(SCRIP-plus).Pharmacotherapy.2005;25(1):110-15.

22.HollandR,BrooksbyI,LenaghanE,etal.Effectivenessofvisitsfromcommunitypharmacistsforpatientswithheartfailure:HeartMedran-domisedcontrolledtrial.BMJ.2007;334(7603):1098.Availableat:http://www.bmj.com/highwire/filestream/366386/field_highwire_article_pdf/0.pdf.AccessedApril9,2012.

23.TheCommunityPharmacyMedicinesManagementProjectEvaluationTeam.TheMEDMANstudy:arandomizedcontrolledtrialofcommunitypharmacy-ledmedicinesmanagementforpatientswithcoronaryheartdis-ease.Fam Pract.2007;24(2):189-200.Availableat:http://fampra.oxfordjourn-als.org/content/24/2/189.full.pdf+html.AccessedApril9,2012.

24.EvansCD,WatsonE,EurichDT,etal.Diabetesandcardiovasculardiseaseinterventionsbycommunitypharmacists:asystematicreview.Ann Pharmacother.2011;45(5):615-28.

25.AmarilesP,FausMJ,JiménezJ,Sabater-HernándezD,García-JiménezE.EfectodelMétodoDáderdeSeguimientoFarmacoterapéuticoenelriesgocardiovasculardepacientesconfactoresderiesgooenfermedadcardiovascular(EMDADER-CV):métodosyresultadosglobales.Ars Pharm. 2008;49(suppl1):7-24.Availableat:http://farmacia.ugr.es/ars/pdf/416.pdf.AccessedApril9,2012.

26.AmarilesP,MachucaM,FausMJ,BaenaMI,Martinez-MartinezF,Jiménez-MartínJ.ApplicationoftheSCOREandWilson-Grundymethodsfortheassessmentofcardiovascularriskincommunitypharmacies.J Clin Pharm Ther. 2008;33(5):475-81.

27.PharmaceuticalCareResearchGroup,UniversityofGranada(Spain).Pharmacotherapyfollow-up:theDaderMethod(3rdrevision:2005).Pharmacy Practice.2006;4(1):44-53.[inSpanish]Availableat:http://scielo.isciii.es/pdf/pharmacy/v4n1/giaf.pdf.AccessedApril9,2012.

28.CommitteeofConsensus.ThirdconsensusofGranadaondrug-relatedproblems(DRP)andnegativeoutcomesassociatedwithmedication(NOM).Ars Pharm.2007;48(1):5-17.Availableat:http://farmacia.ugr.es/ars/ars_web/ProjectARS/pdf/374.pdf.AccessedApril9,2012.


Editors’notetoonlinereaders:AllJMCParticlescontainhyperlinkstothesourcedocumentsforfree-accessreferences.Thesehyperlinksareembeddedinthereferencenumberscitedinthetextaswellasinthelistofreferencesattheendofeacharticle.












http://farmacia.ugr.es/ars/pdf/416.pdf





effectiveness of dader method for pharmaceutical care on ... farmaceuti… · with cvd). secondary...

Documents