Journal of The Association of Physicians of India ■ Vol. 64 ■ July 201614

Management Practices in Indian Patients with Uncontrolled HypertensionRajkumar Bharatia1, Manoj Chitale2, Ganesh Narain Saxena3,  Raman Ganesh Kumar4, Chikkalingaiah5, Abhijit Trailokya6, Kalpesh Dalvi7, Suhas Talele8

1The Apollo Clinic, Guwahati, Assam; 2Consultant, Shree Clinic, Nashik, Maharashtra; 3Dr Saxena’s Clinic, Jaipur, Rajasthan; 4Shreya’s Clinic, New Delhi; 5Sri Rama Clinic, Bangalore, Karnataka; 6Chief Manager, 7Medical Adviser, 8Manager-Clinical Research, Medical Services Abbott Healthcare Private Limited, Mumbai, MaharashtraReceived: 20.02.2016; Accepted: 04.03.2016

O r i g i n a l a r t i c l e

AbstractHypertension (HTN), being a major risk factor for cardiovascular diseases (CVDs), is an important issue of medical and public health. High blood pressure (BP) is ranked as the third most important risk factor for attributable burden of disease in south Asia (2010). Hypertension (HTN) exerts a substantial public health burden on cardiovascular health status and healthcare systems in India. Uncontrolled hypertension among adults with hypertension is associated with increased mortality. An inadequate data is available in India on uncontrolled hypertension.

Objectives: The present study was planned to evaluate the patient profile, co-morbidities, management in uncontrolled hypertensive patients and also to determine the number of patients with resistant hypertension across India.

Methods: A total of 4725 uncontrolled hypertensive patients who were on anti-hypertensive medications were evaluated in this cross-sectional and observational study. The observed patterns were recorded with respect to the prevalence of uncontrolled hypertension and evaluate the socio-demographic, medical history, anthropometric variables and treatment preferences in Indian patients with uncontrolled hypertension.

Results: Majority of the patients with uncontrolled hypertension were males (71.4%) and aged 46-65 years. Most of the study population were pre-obese (males: 35.7%; females: 27.4%). Higher proportion of patients with uncontrolled hypertension were residents of Maharashtra (25.6%) and Gujarat (11.6%). Antihypertensive monotherapy was used by 45.4% and 54.6% patients used combination therapy (≥ 2 categories of anti-hypertensive medications). Angiotensin receptor blockers (ARBs) were the most preferred agent as monotherapy (70.6%) and also the most common component of dual and triple combination anti-hypertensive agent. 19.5% (922/4725) patients had resistant hypertension and 80% of the patients were aged 46-65 years. Higher proportion of patients were males (67.2%; 620/922) and higher proportion of patients were to residents of Andhra Pradesh (21.4% patients) and Maharashtra (19.3% patients). All 922 resistant hypertensive patients were on ≥ 3 anti-hypertensive medications and received ARB + CCB + Diuretics as the

Editorial Viewpoint• U n c o n t r o l l e d

h yp e r t e n s i o n amongadultswithhypertensioni s a s s o c i a t e d w i t hincreasedmortality.

• A l l t h e r e s i s t a n th y p e r t e n s i o np a t i e n t s we r e o n ≥ 3antihypertensivedrugs.

• The protectivemeasuresto be taken to controlhypertensionincludedietand physica l ac t iv i ty ,regularpatientfollow-upand counse l l i ng , andimprovement in drugadherence.

Introduction

Hypertension is considered asoneofthemajorriskfactorsof

cardiovascular(CV)morbidityandmortality.1Itaffectsapproximately26%ofthepopulationworldwide.2Itisresponsibleforatleast45%ofdeathsduetoheartdiseaseand51%ofdeathsduetostroke;accountingfor 9.4million deathsworldwideeveryyear.3-5InIndia,itsprevalencevar ies f rom 20 -40% in urbanadults to 12-17% in rural adults.It is estimated that the numberof peoplewith hypertensionwillincrease to 214 million by 2025,

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016 15

most preferred anti-hypertensive combination therapy. Diabetes and dyslipidaemia were the major comorbidities reported in patients with uncontrolled and resistant hypertension. Lipid lowering agents followed by oral hypoglycaemic agents and antiplatelet medications were the common concomitant medications used. Various factor responsible for not achieving the desired blood pressure goals may be the physician’s lack of awareness about recent hypertensive treatment guidelines that might contribute to patient’s poor adherence due to not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style, the cost of medication, and inadequate dose titration.

Conclusion: Uncontrolled hypertension is a major problem in India. It is prudent to focus on multiple risk factors while treating hypertension. A combination therapy with multiple blood pressure lowering drugs are important and concerns should be identified while selecting the appropriate dosage of combinations of anti-hypertensive therapy and adherence to the therapy. The preferred choices for mono, dual combination and triple combination anti-hypertensive regimens are ARBs; ARB + CCB; ARB + CCB + Diuretics, respectively. In this study, most of the patients were on monotherapy; however a rationale combination therapy or dose adjustment is required for the effective management of hypertension. The protective measures to be taken to control hypertension includes reduction of physicians inertia, diet and physical activity, regular patient follow-up with BP measurements and counselling, and the improvement in patient adherence.

withequalprevalenceinmenandwomen. In India, cardiovasculardisease (CVD) is estimated to beresponsible for 1.5milliondeathsannuallyanditisestimatedthatby2020,CVDwillbethelargestcauseofmortalityandmorbidity.5Recentcommunity surveys conductedon uncontrol led hypertensiondemonstrated that more than 1in 5 adults have uncontrol ledhypertension.6

T h e f a m i l y h i s t o r y o fdys l ip idaemia , d i abe t e s andcigarette smoking are the majorr i s k f a c t o r s a s so c i a t ed w i thhypertension.Theinitialapproachto hypertension management islifestylechanges,includingdietaryinterventions(reducingsaltintake,inc reas ing po tass ium in take ,avoidingalcoholandmultifactorialdiet control), weight reduction,t o b a c c o c e s s a t i o n , p hy s i c a lactivity and stress management.Current antihypertensive therapyincludesdiuretics,β-blockers(BB),calcium channel blockers (CCBs),angiotensin converting enzyme

(ACE) inhibitors and angiotensinreceptorblockers(ARBs).7Previousliterature have reported the clearb ene f i t s o f an t ihype r t ens ivetherapy in loweringCVmortalityandmorbiditybymodestreductionin diastolic and/or systolic bloodp re s su re (BP ) . 8 , 9 Desp i t e t heavailabilityofeffectivetreatments,BP is adequately controlled inminorproportionofthepatients.10-12 The reason for uncontrol ledhypertensionmay be physicians’non-aggressiveandaconservativea p p r o a c h f o r h y p e r t e n s i o ntreatment. The EISBERG projectfound that physiciansweremorefocussed to lower diastolic BP,despite theprovensignificanceofsystolic BP in CV risk.13Anotherwidely recognized reason forinability to achieve BP targets,despitebeingonantihypertensivemedications was patients’ poorc omp l i an c e o r adhe r enc e t otherapy. The EISBERG projectreported that 70% of the primarycare physic ians be l ieved thatpatients’ poor compliance was

themajor reason foruncontrolledhypertension.13 The persistencewi th therapy var i e s be tweendifferentclassesofantihypertensivedrugs;itwassignificantlyhigherinpatients receiving angiotensin IItype1receptorcomparedtootherantihypertensivedrugs.14

Improvement in BP controlleadstoareductioninsubstantialnumber of CV events.As per theNHANES datamore than half ofthe individualswithuncontrolledhyper tens ion a re no t on anyantihypertensive medications;15h owe ve r , m e t a - a n a l y s e s o frandomized cont ro l l ed t r i a l sreported that antihypertensivetherapyreduces theriskofstrokeby approximately 30%, CHD by10-20%,CHFby40-50%,andtotalmortality by 10%.16 Studies haveidentifiedseveralfactorsrelatedtopoorbloodpressurecontrolwhichmaybepatientorphysicianrelated.Patient-related factors includeaccess tohealth care, compliance,andcomorbiditieswhilephysician-relatedfactorsincludeknowledgebase, perceptions about the caredelivered, and practice patterns.Uncontrolled hypertension havebeen assoc ia ted wi th var iouscharacteristics such age, obesity,andlackofexercise.Raceisrelatedto hypertension control as itmayinteractwithmultiplefactorssuchas access to care, susceptibilityto hypertension, and comorbidconditions.Patientnoncompliancemay contr ibute to poor bloodpressurecontrol.17

A patient with uncontrolledhypertension develops resistanthypertensionwhentheBPlevelisabovethegoalinspiteofconcurrentuseof3antihypertensiveagentsofdifferentclasses(oneagentshouldbeadiuretic).Thesepatientswithresistant hypertension can havecontrolledBPlevelsiftreatedwith≥4 medications. The prevalenceo f r e s i s t an t hype r t en s i on i sapproximately 20-30%. Old age,obesityandhighbaseline systolicBP are the most common r iskf ac to r s fo r uncont ro l l ed and

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 201616

resistanthypertension.18Resistanthype r t ens ion c an be t r ea t edby identi f icat ion and reversalof lifestyle factors (dietary saltrestriction,weight loss, cessationor reduction of alcohol intake,i n c r e a s ed phy s i c a l a c t i v i t y ,ingestionofhighfibre,potassiumand calc ium containing diet ) ,appropriatetreatmentofsecondarycausesofhypertension(obstructivesleepapnea,renalarterystenosis)a nd by t h e u s e o f mu l t i p l eantihypertensivemedications.The r e a r e l im i t ed s t ud i e s

o n p a t i e n t s w i t h r e s i s t a n thypertension as these patientshaveahighCVrisk,aregenerallyassociatedwithmultiple diseasesand tough enrolment. In absenceof any large data from India ,the exact prevalence of resistanthypertension is still unknown.Hence, the present s tudy wasplannedtoexploretheprevalenceof res is tant hypertension andevaluate the socio-demographic,medical history, anthropometricvariablesandphysiciantreatmentpreferencesinIndianpatientswithuncontrolledhypertension.

Material and MethodsStudy design

This was a c ross -sec t ional ,multi-centric, non-interventional,observat ional and s ingle vis i tstudy conducted across 486 sitesinIndiaduringtheyear2013-2014.The eligibility criteria includedmale and female patients withuncontrolled hypertension, whowereonanti-hypertensivetherapy,agedbetween18to65years,visitedforaroutinevisittotheirphysicianandwerewillingtosignthepatientauthorizationform.Thosepatientswho required hospitalization forany cause or were pregnant orlactatingwere excluded from thestudy.Uncontrolled hypertensionwasdefinedasinabilitytoachievethe systolic blood pressure <140(mmHg) and d ia s to l i c b loodpressure <90 (mmHg) as perJo int Nat ional Committee VII

gu ide l ines , desp i t e be ing onanti-hypertensive medications.Resistanthypertensionwasdefinedas blood pressure that remainselevated above treatment goalsdespite concurrent use of 3 anti-hypertensivemedicationsofdifferentclassesthatincludesadiuretic.19

Thefinalprotocolwasapprovedby respective institutional ethicsc omm i t t e e . T h e s t u d y wa sconducted in accordance withthe Dec l a ra t i on o f He l s ink i ,I n t e rna t i ona l Con f e r ence onHarmonization of Good ClinicalPracticeguidelines,IndianCouncilofMedical Research, IndianGCPguidelines,andapprovedprotocol.Study assessments

During the routine visit to thephysician, the investigatororhis/herdesignee collected thepatientdataonAbbottdatacollectionformtogatherinformationonpatient’ssocio demographic factors (age,gender,stateofresidence,educationandoccupation),lifestylepractices(smoking, alcohol consumption,tobaccochewing,anddiet),medicalhistory (diabetes, hypertension,ischemicheartdisease,congestivehear t fa i lure , chronic k idneyd i s e a s e , d y s l i p i d a em i a a ndhormone replacement therapy inwomen),treatmenthistoryofanti-hypertensivemedications likeBB,alpha blockers, ACE inhibitors,ARBs, diuretics, centrally actingdrugs, CCBs and others , vi talparameters (systolic anddiastolicBPandpulserate),anthropometricvariables (weight, height, waistand h ip c i r cumfe r en c e , andbody mass index [BMI] ) , andconcomitant medications (oralcontraceptive pills, non-steroidalanti-inflammatorydrugs,steroids,oral hypoglycaemic agents, lipidlower ing agents , an t ip la te le tmedications,andothers).Study Endpoints

The primary study endpointsw e r e d e m o g r a p h i c a n danthropometricvariables,medicalhistory,andvitalparameters.Thesecondary study endpoints were

treatmenthistory,currenttreatmentandconcomitantmedicationsused.Inaddition,patientswithresistanthyper tens ion were eva lua tedin terms of their demographiccharacteristics,medicalhistoryandcurrenttreatment.Statistical analysis

N o f o r m a l s a m p l e s i z eca l cu la t ion was done as th i swas an observational and non-interventional study.All enrolledpatients constituted the analysispopulation.ThestatisticalanalysiswasdoneusingStatisticalAnalysisSystem® vers ion 9 .3 sof tware .The continuous variables weresummarizeddescriptivelybymean,standard deviation, median andrange. The categorical variablesweredescribedbyfrequenciesandpercentages.

ResultsPatient Demographics

A total of 4814 patients withuncontrolled hypertension wereassessed for eligibility. Of these,4725(98.2%)patientswhomettheeligibility criteria were enrolledin this study, and constituted theanalysispopulation.Themeanage,weight,height,waistcircumference,hipcircumference,andBMI,ofthepatientpopulationwas51.2±8.64years,71.6±11.77kg,162.3±9.10cm,90.5±10.29cm,96.6±13.97cm,and27.3±4.41kg/m2,respectively.Thesystolic,diastolicBPandpulserateofthepatientpopulationwas158.70 ± 14.498mmHg and 97.93±9.352mmHg,and83.16±8.373bpm, respectively. The majorityof the patients were educated(post-graduates/highersecondary/secondary; 57.2%), vegetarians(71.5%), non-smokers (83.9%),non-alcoholic(86.6%),non-tobaccochewers(90.3%)andhadanoutdoorlifestyle(68.3%).Themeandurationofsmoking,alcoholconsumption,and tobacco chewingwas 14.52 ±9.196years,13.37±8.537years,and13.55 ± 8.787 years, respectively.Higherproportionofpatientswereresidents ofMaharashtra (25.6%)

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016 17

Fig. 1A: Patient’s demographics: Gender-wise proportion in each age category (N = 4725) Fig. 1B: Patient’s demographics: Medical history

(uncontrolled hypertension) (N = 4725)

Fig. 1C: Patient’s demographics: Age and gender-wise distribution of mean systolic blood pressure (N = 4725)

Fig. 1D: Patient’s demographics: Age and gender-wise distribution of mean diastolic blood pressure (N = 4725)

Fig. 1E: Patient’s demographics: Patients taking two or more anti-hypertensives (N = 4725)

Fig. 1F: Patient’s demographics: Proportion of patients taking two or more antihypertensives (N = 2578)

1600

1400

1200

1000

800

600

400

200

018-25 26-35 36-45 46-55 56-65

1(0.0%)

3(0.1%)

78(1.7%)

143(3%)

322(6.8%)

708(15%)

487(10.3%)

1343(28.4%)

461(9.8%)

1179(24.9%)

Female

Male

No.

of S

ubje

cts

(per

cent

age)

18001600140012001000800600400200

0No.

of s

ubje

cts

(per

cent

age)

33(0.7%)

Chronic Kidney

Dise

ase (C

KD)

Congestive H

eart

Failure

(CHF)

Diabete

sDysli

pidemia

HRT (Women

)

Ischem

ic Hea

rt Dise

ase (IH

D)Hypothyroidism

Acid-Pep

tic D

isease

Others

1593(33.7%)

496(10.5%)

7(0.1%)

152(3.2%) 6

(0.1%)4

(0.1%)26

(0.6%)28

(0.6%)

180.00

175.00

170.00

165.00

160.00

155.00

150.00

145.00

140.0018-25 26-35 36-45 46-55 56-65

Age Class

SBP

(mm

Hg)

Mea

n V

alue

158.00

174.00

152.90

153.91158.35

156.32 159.75158.94 161.38

159.40Female

Male

104.00

102.00

100.00

98.00

96.00

94.00

92.00

90.00

DBP

(mm

Hg)

Mea

n V

alue

96.00

103.33

95.41

97.25 98.04

98.75

97.90

98.57

96.13

97.62

Female

Male

18-25 26-35 36-45 46-55 56-65Age Class

1600

1400

1200

1000

800

600

400

200

0

1497(31.7%)

879(18.6%)

179(3.8%)

22(0.5%)

1(0.0%)

Two Three Four Five Six

No.

of S

ubje

cts

(per

cent

age)

600

500

400

300

200

100

0

CC

B+A

RB

Two ThreeNo. of Anti-Hypertensive Medications

Four Five Six

Diu

+ARB

BB+A

RB

CC

B+BB

Diu

+AC

Ei

Diu

+CC

B+A

RB

Diu

+BB+

ARB

CC

B+BB

+ARB

Diu

+CC

B+BB

Diu

+CC

B+A

CEi

Diu

+CC

B+BB

+ARB

Diu

+CC

B+BB

+AC

Ei

Diu

+CC

B+A

CEi

+ARB

Diu

+CC

B+BB

+AC

Ei+A

RB

Diu

+CA

D+C

CB+

BB+A

RB

Diu

+CC

B+BB

+AB+

AC

Ei+A

RB

No.

of S

ubje

cts

(per

cent

age)

506(33.8%)

428(28.6%)

235(15.7%) 197

(13.2%)

26(1.7%)

522(59.4%)

133(15.1%)

124(14.1%)

33(3.8%) 13

(1.5%)

126(70.4%)

11(6.1%)

11(6.1%)

17(77.3%)

4(18.2%)

1(100%)

and Gujarat (11.6%).Majority ofthepopulation (71.4%, 3376/4725)weremales andaged46-65years.Majority of the patients (bothmalesandfemales)werepre-obese(males: 35.7%; females: 27.4%)and higher proportion of femaleswere obese than males in agecategory46-65years(23.8%versus16.9%).Patient’sdemographicsaresummarizedinFigure1.VitalsignsarepresentedinTable1.O f 4 7 2 5 p a t i e n t s w i t h

uncontrolled hypertension, 922(19.5%) patients with mean age

52.6 ± 8.25 years had a resistanthypertension. 80%of the patientswereaged46-65years.Thehigherproportionofpatientsweremales(67.2%; 620/922), educated (63%)and employed (52.4% patients).Higher proport ion of pat ientswereresidentsofAndhraPradesh(21.4%), Maharashtra (19 .3%),Ra j a s than ( 13 . 9%) and Ut t a rPradesh (12.8%).The mean BMIwas comparable between malesandfemales.Diabetesanddyslipidemiawere

themajor comorbidities reported

inpatientswithuncontrolledandresistant hypertension. Both thedisorders weremajorly reportedin patients of age category 46-65years.

Current Treatment

Anti-hypertensivemonotherapywas used by 45.4% (2147/4725)patients and 54.6% (2578/4725)patients used the combinationtherapy (≥ 2 categories of anti-hypertensivemedications)where1497 (58.1%)patients, 879 (34.1%)patients, 179 (6.9%) patients, 22

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 201618

Fig. 1I: Pie chart representing age-wise distribution of resistant hypertensive patients (N = 922)

Fig. 1J: Patient’s demographics: Proportion of resistant hypertensive patients taking three or more anti-hypertensive medications (N = 922)

(0 .9%) pat ients , and 1 pat ientuseddual, triple, 4, 5 and 6 drugc omb i n a t i o n s , r e s p e c t i v e l y .Angiotensin receptor blockerswasthemostcommonsingledrugcategory(70.6%)followedbyCCBsand BB (11.5%).Olmesartan (45%patients) and Telmisartan (21%patients)(bothARBs)werethemostcommonlyusedanti-hypertensivemono th e r apy . O lme sa r t an +Amlodipine(CCB)(66%;334/1497patients) followed byOlmesartan+Hydrochlorothiazide (diuretics)(57%; 244/1497 patients) was themost commondual combinations;O lmesa r t an + Amlod ip i n e +H yd r o c h l o r o t h i a z i d e ( 8 0% ;416/879 patients) was the mostcommon tripledrug combination;Amlodipine+Hydrochlorothiazide

Table 1: Summary of vital signs

Parameter Mean ± SDSystolicbloodpressure(mmHg)

158.70±14.498

Diastolicbloodpressure(mmHg)

97.93±9.352

Pulserate(bpm) 83.16±8.373

+Metoprolol (BB) + Olmesartan(46%; 58/179 patients) was themostcommon4drugcombination;Amlodipine + Enalapri l (ACEinhibitor ) + Hydrochlorothiazide+Metoprolol+Olmesartanwasthemostcommon5drugcombination( 2 3% ; 5 / 2 2 p a t i e n t s ) ; a nd 1patient used the combination ofAmlodipine+Atenolol+Enalapril+Hydrochlorothiazide+Olmesartan+ Prazosin. State-wise, the mostcommon dual drug combinationwas CCB + ARB in the state ofMaharashtra (28% patients) andGujarat(44%patients),BB+ARBinthe stateofAndhraPradesh (38%patients),andDiuretics+ARBinthestate of Rajasthan (54% patients).The most common tr iple drugcombinationwasDiuretics +CCB+ARB acrossMaharashtra (47%patients),Andhra Pradesh (84%patients), Gujarat (35% patients),andRajasthan(50%patients).All 922 resistant hypertensive

p a t i e n t s we r e o n ≥ 3 a n t i -hypertensive medications; 732

( 7 9%) , 1 6 7 ( 1 8%) , 2 2 ( 2 . 4% )and 1 (0.1%) patients were oncombinat ion o f 3 , 4 , 5 and 6anti-hypertensive medications,respectively.CCB+ARB+diuretics(71%;522/732patients),CCB+BB+ARB + diuretics (75%; 126/167patients),CCB+BB+ACEinhibitor+ ARB + diuret ics (73%; 16/22patients), and CCB + BB + alphablockers+ACEinhibitors+ARB+diuretics (1patient)was themostcommonly used triple, 4, 5 and 6drugcombinations,respectively.

Concomitant Medication

Th e d a t a o f c o n c om i t a n tmedicat ions was avai lable for1284/4725 (27%) patients. Lipidlowering agents (59%; 751/1284p a t i e n t s ) f o l l owed b y o r a lhypog ly caemi c agen t s ( 5 1% ;652/1284patients)andantiplateletmed i c a t i on s ( 2 3% ; 3 0 1 / 1 2 8 4p a t i e n t s ) we r e t h e c ommonconcomitant medications usedby the patient population. Morethan 20% of the patients were

1(0.1%) 32

(3.5%)

151(16.4%)365

(39.6%)

373(40.5%)

18-25

26-35

36-45

46-55

56-65

Fig. 1G: Patient’s demographics: Patients taking two anti-hypertensive medications (N = 1497) Fig. 1H: Patient’s demographics: Patients taking three

anti-hypertensive medications (N = 879)

400350300250200150100500

No.

of s

ubje

cts

(per

cent

age)

24(10.2%)

Ate

nolo

l+Te

lmis

arta

n

ARB + BB ARB + CCB ARB + Diu BB + CCBCombination of Anti-Hypertensive Medication type

Met

opro

lol+

Olm

esar

tan

Ate

nolo

l+O

lmes

arta

n

Met

opro

lol+

Telm

isar

tan

Am

lodi

pine

+Los

arta

n

Am

lodi

pine

+Tel

mis

arta

n

Am

lodi

pine

+Olm

esar

tan

Chl

orta

lidon

e+O

lmes

arta

n

Hyd

roch

loro

thia

zide

+Los

arta

n

Hyd

roch

loro

thia

zide

+Te

lmis

arta

n

Hyd

roch

loro

thia

zide

+Olm

esar

tan

Am

lodi

pine

+Ate

nolo

l

Am

lodi

pine

+Met

opro

lol

105(44.7%) 41

(17.4%)42

(17.9%) 22(4.3%)

132(26.1%)

334(66%)

34(7.9%)

13(3%)

83(19.4%)

244(57%)

148(75.1%)

39(19.8%)

450

400

350

300

250

200

150

100

50

0

No.

of s

ubje

cts

(per

cent

age)

24(19.4%)

Am

lodi

pine

+Met

opro

lol+

Olm

esar

tan

Am

lodi

pine

+Met

opro

lol+

Telm

isar

tan

ARB + BB + CCB ARB + BB + Diu ARB + CCB + Diu BB + CCB + DiuCombination of Anti-Hypertensive medication type

Am

lodi

pine

+Ate

nolo

l+O

lmes

arta

n

Hyd

roch

loro

thia

zide

+Met

opro

lol+

Telm

isar

tan

Hyd

roch

loro

thia

zide

+Met

opro

lol+

Olm

esar

tan

Chl

orta

lidon

e+M

etop

rolo

l+O

lmes

arta

n

Ate

nolo

l+H

ydro

chlo

roth

iazi

de+

Telm

isar

tan

Am

lodi

pine

+Hyd

roch

loro

thia

zide

+Te

lmis

arta

n

Am

lodi

pine

+Hyd

roch

loro

thia

zide

+O

lmes

arta

n

Am

lodi

pine

+Chl

orta

lidon

e+O

lmes

arta

n

Am

lodi

pine

+Ate

nolo

l+H

ydro

chlo

roth

iazi

de

Am

lodi

pine

+Hyd

roch

loro

thia

zide

+M

etop

rolo

l

41(33.1%)

39(31.5%) 13

(9.8%)

38(28.6%) 12

(9%)21

(15.8%)

55(10.5%)

416(79.7%)

13(2.5%)

15(45.5%)

4(12.1%)

600

500

400

300

200

100

0

522(71.3%)

133(18.2%)

CCB+ARB+Diu

BB+ARB+Diu

CCB+BB+Diu

CCB+ACEi+Diu

CCB+BB+ARB+Diu

CCB+BB+ACEi+Diu

CCB+ACEi+ARB+Diu

CAD+BB+ARB+Diu

CCB+BB+ACEi+ARB+

Diu

CAD+CCB+BB+ARB+

Diu

Five SixThree FourNo. of Anti-Hypertensive Medication Types

CCB+BB+AB+ACEi+ARB+Diu

33(4.5%) 13

(1.8%)

126(75.4%)

11(6.6%)

10(6%)

6(3.6%)

16(72.7%)

4(18.2%)

1(100%)

No.

of S

ubje

cts

(per

cent

age)

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016 19

on Metformin (32% pat ients ) ,Ato rva s t a t i n ( 3 0% pa t i en t s ) ,Rosuvastatin (27% patients) andGlimepiride(23%patients).

Discussion

Previous studieshave reportedvariedprevalenceofhypertensionacross different states in India;7 .24% in rural Maharashtra , 203.41%inRuralSevagram,217.8%inMumbai hospitals,22 and 8.6% inanurbanslumTirupathi.23 In thisstudy, majority of uncontrolledhypertensivepatientswereamongthe residents ofMaharashtra andGujarat which could possibly bedue to environmental factors andlifestyle differences in differentgeographicalregionsinIndia.Factorssuchasage,BMI,obesity,

diabetes, smoking, alcohol andtobacco intake, dietary habits,lifestyleandstressarethecommonrisk factors for hypertension.Oldor increasing age is one of thestrongest risk factor associatedwith uncontrolled and resistanthypertension, which could bepossiblybecauseofatheroscleroticchangesoccurringinbloodvesselswithaging,especiallyunderstress,unknown factors and increasedpreva lence o f r i sk f ac tors o fhypertension in males.24 In thisstudy, 73% of the patients haduncontrolled hypertension and80% of the patients had resistanthypertension in the age group of46-65years.Obesityisanotherriskfactorassociatedwithuncontrolledandresistanthypertension.Mostofthepatientsinourstudywereeitherpre-obeseorobeseandtherewasasignificantcorrelationofincreasingbody weight with hypertension.Th e s e o b s e r va t i on s we r e i nconcordancewith2epidemiologystudiesconductedinChennaiandBangalore reporting age, obesityand gender as the strongest riskfactors for hypertension.24,25 Themean BMI in the present studywas 27.3 ± 4.41 kg/m2,whichwasmuch higher than the suggestedcutoffof23kg/m2inAsianIndianadults,26whichsuggestsoverweight

asthemainmodifiableriskfactor.Alcoholism and smoking historywaspresentin13.4%and16.1%ofthe studypopulation.Our resultswereinconcordancetotheearlierreportedstudywherealcoholandcigaretteaddictionwasreportedin13.2%ofthehypertensivepatients.27

The causes of uncontrol ledhypertensionmaybeeitherpatientre la ted or phys i c ian re la ted .Patient related factors includesrestricted access to healthcare,i n c r e a s e d s u s c e p t i b i l i t y t ohypertension (advanced age andobes i ty) , noncompliance withtherapy (knowledge de f i c i t s ,medica t ion cos t , compl ica tedr eg imens , s ide e f f e c t s , poo rphysician patient communicationand l a ck o f so c i a l suppor t ) ,and resistant hypertension. Onthe contrary, physician factorsincludes inadequate knowledgeabout guidelines (BP threshold,isolated systolic hypertension,threshold for diabetic patient,useofmonotherapyinpatientsinwhom BP is difficult to control),ove re s t ima t ion o f adherencet o gu ide l i n e s , d i s ag r e emen twith guidelines, concern aboutmedicationsideeffects,beliefthatofficeBPtrendstobehigher thanhome BP, reluctance to treat anasymptomatic condition and lackof time at office visits.17 Despiterecognizing that BP are elevated,physic ians may choose not toadvance therapy. Several reasonshavebeensuggestedforthisclinicalinertia such as overestimation ofadherence to guidelines, lack ofpractice supports to facilitate theachievement of target BP, anduse of soft justifications to avoidadvancing care for asymptomaticpatients.28

Indians have excessive dietarysaltingestionduetoconsumptiono f e t hn i c I nd i an f o od s l i k echutneys, papads, and pickleswhich are the regular householdchoicesthatincreasedailysodiumconsumption and predisposesthe population to hypertensionfol lowed by uncontrol led and

resistanthypertension.20Excessived i e t a ry sod ium in t ake l e adst o d eve l opmen t o f r e s i s t an thypertension by either directlyincreasing the BP or decreasingthe BP lowering effect ofmost ofthe antihypertensive agents.29,30Overal l , 19.5% of the patientswith uncontrolled hypertensiondevelopedresistanthypertension.Recent years havewitnessed a

rapid increase in the prevalenceof diabetes and hypertension inIndia with diabetes being oneof the major comorbidi t ies inhypertensivepatients,whichmaybe attributed to the increasinglevels of sedentary l i fe s tyle ,urbanization,andconsumptionofenergy rich and poor fiber food.Screening India’s Twin Epidemic(SITE) study have shown thatdiabetesandhypertensioncoexistsin 21% patients; concluding thedoub l e j eopa rdy o f d i abe t e sand hyper tens ion to b las t anexplosion of CV complications.31T h e s e r e p o r t s a r e f u r t h e rsubstantiatedbyanepidemiologys tudy conducted in Chennai ,where d iseases l ike d iabetes ,obesity, hypercholesterolemia,hypertriglyceridemia, abdominalandgeneralobesitywerehigherinhypertensivepatientsascomparedto normotensive patients.25 Wealso observed diabetes to be themajor comorbidi ty assoc iatedwi th uncont ro l l ed (47%) andresistanthypertension(34%).Othercomorbid condit ions observedweredyslipidemia,ischemicheartdisease, chronic kidney disease,congestiveheart failure, hormonereplacement therapy which arereported to occur in hypertensivepatients.31

An t ihype r t ens ive the rapy ,includingACE inhibitors,ARBs,CCB s , d i u r e t i c s a nd n ewe rα-blockers , have shown c learbenefits in terms of reducing theCVmortality andmorbidity.9 In1995, Materson et al . reportedadditive antihypertensive benefitbycombinationof2medicationsofdifferentclasses.32Fewearlierreports

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 201620

have also suggested significantadd i t i on a l a n t i hype r t e n s i vebenefit ofACE inhibitor +ARB/CCB over monotherapy wi thdifferent agents. 33,34 In 2013, itwas reported thatBP target goalscanbeachievedwithtwoormoredrugs in 60-70% of patients.35 Inthis study, 45% patients receivedmonotherapywhile 55% patientsreceived combination therapy;sugges t ing tha t combina t iontherapy is required in most ofthe patients with hypertension.It is important to find out therightmonotherapyorcombinationtherapy with appropriate dosesfor each individual hypertensivepatient.36In2000,Chaputcomparedpersistency of ARBs over otherantihypertensive agents in 25000patients included in a Canadiandatabase and reported that thethat persistencewas significantlyhigher among patients treatedwith ARBs compared to otherantihypertensivemedicationsby24months.14Thisstudyalsoreportedthe similar results whereARBs(Olmesartan and Telmisartan)were the most commonly useda g e n t s a s m o n o t h e r a p y o ra component of combinat ionstherapy;whichmay be due to itshigher persistence owing to itsbettertolerabilityandeffectivenessoverotherantihypertensiveagents.The combination ofARBs, withCCBs and/ or Diuret ics is thecommonly used antihypertensiveinhypertensionmanagement.Conclusion

Uncont ro l l ed hyper tens ionis a major problem in India. Anumberoffactorscontributetothevariation inhypertension control.The reason for poor control isthe heterogeneous populat ionincluding patient characteristics( a g e , o b e s i t y ) , c o - m o r b i dconditions,concomitantmedicines,and treatment patterns whichpresumably contribute directlyto control blood pressure. It isprudent to focus onmultiple riskfactorswhiletreatinghypertension.A combina t ion the rapy wi th

multiple BP lowering drugs isimportant and concerns shouldbe identified while selecting thecombinationsofanti-hypertensivethatarelesseffectiveonthebasisofefficacyandtolerability.Co-morbidconditionssuchasdyslipidemiaordiabetes are majorly associatedwith uncontrolled and resistanth yp e r t e n s i o n . T hu s s p e c i a lattention is required for thosewith hypertension co-exist ingw i t h d i a b e t e s me l l i t u s a nddyslipidaemiasincepoorcontrolofbothconditionsincreasestheirriskfor cardiovascular complications.Monotherapyistheleadingtrendofanti-hypertensivetherapyfollowedby dual combination and triplecombination anti-hypertensiveregimens. The preferred choicesf o r mono , dua l comb ina t i onand t r ip l e combina t ion an t i -hypertensive regimens areARBs;ARB+CCB;ARB+CCB+Diureticsrespectively. The preferred anti-hypertensivetherapyforresistanthypertensive patients is tr iplecombination of anti-hypertensiveregimenARB + CCB + Diuretics.Inthisstudy,mostofthepatientswere on monotherapy; howevera rationale combination therapyor dose adjustment is requiredfor the e f fec t ive managementof hypertension. The protectivemeasures to be taken to controlhypertensionincludesreductionofphysiciansinertia,dietandphysicalactivity,regularpatientfollow-upw i t h BP mea su r emen t s a ndcounselling,andtheimprovementinpatientadherence.Acknowledgements

Theauthorswouldliketothankall doctors who participated inthis study. The authors woulda lso l ike to acknowledge s i temanagemen t o rgan i za t i on &medical writ ing agency (Max-Neeman International) and datamanag emen t a g en c y ( P r i smBiomed)fortheirefforts.Disclosure

ThisstudywasfundedbyAbbottHealthcare Pvt. Ltd. Dr.AbhijitTrailokya,ChiefManager-Medical

Se rv i ce s , Dr . Ka lpesh Da lv i ,MedicalAdvisor-MedicalServices,Mr.SuhasTalele,Manager-ClinicalResearch,MedicalServicesallareemployees ofAbbott HealthcarePrivateLimited,Mulund,Mumbai.

References1. M a k r i d a k i s S , D i N i c o l a n t o n i o J J .

Hypertension: empirical evidence and implications in 2014.  Open Heart 2014; 1:e000048.

2. Kearney PM,  Whelton M,  Reynolds K,  Muntner P, Whelton PK,  He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365:217-223.

3. Causes of death 2008: data sources and methods. Available from: http://www.who.int/healthinfo/global_burden_disease/cod_2008_sources_methods.pdf

4. Lim 2010 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380:2224-2260.

5. Bansal SK,  Saxena V,  Kandpal SD,  Gray WK, Walker RW, Goel D. The prevalence of hypertension and hypertension risk factors in a rural Indian community: A prospective door-to-door study. J Cardiovasc Dis Res 2012; 3:117-123.

6. Musinguzi G, Van Geertruyden JP, Bastiaens H,  Nuwaha F. Uncontrolled hypertension in Uganda: a comparative cross-sectional study. J Clin Hypertens (Greenwich) 2015; 17:63-69.

7. Gupta R, Guptha S. Strategies for initial management of hypertension. Indian J Med Res 2010; 132:531-542.

8. Isles CG, Walker LM,  Beevers GD, et al. Mortality in patients of the Glasgow Blood Pressure Clinic. J Hypertens 1986; 4:141-156.

9. MacMahon S, Rodgers A. The effects of antihypertensive treatment on vascular disease: reappraisal of the evidence in 1994. J Vasc Biol Med 1993; 4:265-271.

10. Mancia G, Grassi G. Rationale for the use of a fixed combination in the treatment of hypertension. Eur Heart J 1999; 1: L14-L19.

11. Primatesta P, Brookes M, Poulter NR. Improved hypertension management and control. results from the health survey for England 1998. Hypertension 2001; 38:827-832.

12. Wang TJ,  Vasan RS. Epidemiology of uncontrolled hypertension in the United States. Circulation 2005; 112:1651-1662.

13. Swales JD. Current clinical practice in hypertension: the EISBERG (Evaluation and Interventions for Systolic Blood pressure

Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016 21

Elevation-Regional and Global) project. Am Heart J 1999; 138:231-237.

14. Chaput AJ. Persistency with angiotensin receptor blockers (ARB) versus other antihyper tensives (AHT ) using the Saskatchewan database. Can J Cardiol 2000; 16:194F (abstract 390).

15. Hajjar I, Miller K, Hirth V. Age-related bias in the management of hypertension: a national survey of physicians’ opinions on hypertension in elderly adults. J Gerontol A Biol Sci Med Sci 2002; 57:M487-M491.

16. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289:2534-2544.

17. Wang TJ, Vasan RS. Epidemiology of uncontrolled hypertension in the united states. Circulation 2005; 112:1651-1662.

18. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008; 117:e510-e526.

19. National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Available from: http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf

20. Todkar SS, Gujarthi VV, Tapare VS. Period prevalence and socio demographic factors of Hypertension in Rural Maharashtra, a cross sectional study. Indian J Community Med 2009; 34:183-187.

21. Jajoo N, Kalantri P, Gupta P, Jain P, Gupta K.  Prevalence of hypertension i n r u r a l p o p u l a t i o n   a r o u n d sevagram MGM, Wardha. JAPI 1993; 41:422-424.

22. Joshi V, Patel C, Dhar HL. Prevalence of hypertension in Mumbai. Indian J Med Sci 2000; 54:380-383.

23. Reddy SS, Prabhu GR. Prevalence and risk factors of hypertension in adults in an urban slum, Tirupati, A.P. Indian J Community Med 2005; 30:84-86.

24. Madhukumar S, Gaikwad V, Sudeepa D. An epidemiological study of hypertension and its risk factors in rural population of Bangalore rural district. Al Ameen J Med Sci 2012; 5:264-270.

25. Mohan V,  Deepa M,  Farooq S,  Datta M,  Deepa R. Prevalence, awareness and control of hypertension in Chennai--The Chennai Urban Rural Epidemiology Study (CURES-52). J Assoc Physicians India 2007; 55: 326-332.

26. S n e h a l a t h a C , V i s w a n a t h a n V , Ramachandran A. Cutoff values for normal anthropometric variables in Asian Indian adults. Diabetes Care 2003; 26:1380-1384.

27. Mahajan H, Kazi Y, Sharma B, Velhal GD. Assessment of KAP, risk factors and associated co-morbidities in hypertensive patients. IOSR-JDMS 2012; 1;6-14.

28. Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med 2001; 135:825-834.

29. Luft FC, Weinberger MH. Review of salt restriction and the response to a nt i hy p e r te n s i ve d r u g s : S ate l l i te symposium on calcium antagonists. Hypertension 1988; 11:I229-I232.

30. Weinberger MH, Cohen SJ, Miller JZ, Luft FC, Grim CE, Fineberg NS. Dietary sodium restriction as adjunctive treatment of hypertension. JAMA 1988; 259:2561-2565.

31. Joshi SR,  Saboo B,  Vadivale M,  et al. Prevalence of diagnosed and undiagnosed diabetes and hypertension in India - results from the Screening India’s Twin Epidemic (SITE) study. Diabetes Technol Ther 2012; 14;8-15.

32. Materson BJ, Reda DJ, Cushman WC, Henderson WG. Results of combination anti-hypertensive therapy after failure of each of the components. Department of Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents. J Hum Hypertens 1995; 9:791-796.

33. Saseen JJ, Carter BL, Brown TE, Elliott WJ, Black HR. Comparison of nifedipine alone and with diltiazem or verapamil in hypertension. Hypertension 1996; 28:109-114.

34. Stergiou GS, Skeva II, Baibas NM, et al . Addit ive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension. J Cardiovasc Pharmacol 2000; 35:937-941.

35. Management of hypertension. Supplement to JAPI 2013; 61:17-23.

36. Trailokya A, Patel K, Dalvi K. Management practices in hypertension: results of WIN-OVER - A Pan India Registry. Indian Medical Gazette 2015; 149:62-67.

37. Neutel JM, Smith DHG. Hypertension management: rationale for triple therapy based on mechanisms of action. Cardiovasc Ther 2013; 31:251-258.