Efficacy and safety of losartan versus calcium channel blockers in hypertension

Efficacy and safety of losartan versus calcium channel blockers in hypertension

AJH-APRIL 1997-VOL. 10, NO. 4, PART 2 SPECIAL SYMPOSIA Wednesday May 28, Ballroom A, 12:00 pm ACE Inhibitors, Diabetes, and Obesity: Molecules, Meta...

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AJH-APRIL 1997-VOL. 10, NO. 4, PART 2

SPECIAL SYMPOSIA

Wednesday May 28, Ballroom A, 12:00 pm ACE Inhibitors, Diabetes, and Obesity: Molecules, Metabolism, and Management

Wednesday May 28, Ballroom A, 12:00 pm ACE Inhibitors, Diabetes, and Obesity: Molecules, Metabolism, and Management

HYPERTENSION AND DIABETES MELLITUS. Michael L. Tuck, M.D. Sepulveda VA Medical Center and [JCLA School of Medicine, Los Angeles, CA. Several factors in the diabetic state appear to contribute to the high incidence of hypertension (HT). Abnormalities early in the conrse of diabetes (DM) include Na+retention and vascular hyperreactivity. Studies of exchangeableNa+ show an increase of 10°/0in DM versus controls. The Na+ retention is due mostly to an increased tubular reabsorption of Na+. Increased blood pressure responses to stress or pressor stimuli (Ang II, norepinephrine) are seen in subjects with DM before the onset of HT or other complications. This vascular response has been explained by abnormal Ang 11action and Na+retention. Obesity may accentuate the vascular and Na’ responses. The renin-angiotensin system (R4S) is classically thought to be depressed in DM as assessed by circulating values. In contrast, intrarenal rcnin protein content, and renin and Ang 11mRNA are increased in DM rats despite normal blood levels. The disproportionate activation of the intrarenal IL4S in DM may explain the prominent hemodynamic response to ACE inhibitors and AT, receptor antagonists. Early hemodyttamic maladaptations in DM include a generalized systemic vasodilation and increased glomerulw capillary pressure. Insulin has been implicated in HT in NIDDM as it favors Na retention and nerrrogenic activation. However, insulin’s direct effect on blood vessels is as a vaaodilator through very specific ~tions to block pre=or hormone-mediated calcium transients in vascular smooth muscle cells. Other factors implicated in diabetic HT include atrial natriuretic peptide, the Na-H antiporter, and neurorud turnover.

DIABETIC CARDIOVASCULAR DISEASE AND THE ANG1OTENSINI-CONVERTING ENZYME: ROLE fN PATHOGENESIS AND TREATMENT

Key Words:

Diabetes, hypertension, insuhtL ralgiotettsitt

Saturday May 31, Ballroom B, 5:30 pm Patient Tolerability in Hypertension Management—Clinical Insights of an AII Antagonist EFFtC.ACYAND WEtYOFLDSAJ?TAN VERSUS CALCIUM CHANNEL BLOCKERS IN HYPERTENSION. JAR. Weir. University of Maryfand School of Medicine, Battimore,MD. Twr~mta randomized,[email protected] group, mattkxnt ar ctinicdtriate were conducted to eomperefhe afkacy, tolerabitii, and affects on quality of Me aaecciatad wtththe angiotenainII receptor antagonistIcaarten alone or with HCTZ end aither the dihydropyridinecalcium channd blocker nifedidne GITS alone, or amlodipine,alone or tih HCTZ. Theaa studies were conduciad in p~enta whose atthg diastolic btood pressure measurements were between 95 and 115 mmHg induatve after Mce.Mng @acabofcra parbdcffOurwwka. Inthefiratdinicdfrtal, 110patfantswere randomhdto recaivaIbeatininittalty givenat50 mgonceparday. This could be titrated to Ioeartan 50 [email protected] 12.5 mg qd after four weeks fdtowd bybsetin 50 mgJHCTZ25 mg qd after aightweeka as nameaary 113 patianta ware randomized to remkve nifadipineGITS. They could radva30mgqdwhkh could bbtmtadto60 mg qd eftar4 waaka and 90 ry to mg qd after 8 weaka. Medication wee titrated upward as n~ achieve a sittingdaatohc Mood pressure leas than 90 mmHg. Eflieacy, tolerability and quatityof life scores wara smeaeed after twatve weeks of each therapy. Trough sittingdiastolicMood pressure measurements after 4,8, and 12 weeks of therapy were almost identical:Iaaanan regimen -8.9, -11.6, and -12.7 mmHg, raspaetivaiy, and niadipine GITS, -9.3, -11.0, 11.1 mmHg, raapectiveiy. Fourteen p~anta in the nhrtipine GITS group waretidrawn due to adveraa events (8 dua to edema) and ski petiantain the bsarhn groupwerewtttrdmwn due to an adverse avent. In the second &Jcatstudywhich had identicalatudy design as the firatatudy, 98 patienta wera randomizedto the Iosartan regimanwhereaa 93 wara randomizedto the amledpina regimen. The baarten regimen weathe same as in the fitst atudy. The other pWenta were started on amlodipine5 mg qd. After four weatrsthayeculd be titratedto amlodipine10 mg qd, and eftar dghtwaaka amlodipine 10 mg qd f.WaHCTZ 25 mg. Blood pressure reductionin the two groups after twatve weeka of therapy was identicalwith no statidical d“fierencaafor eitherayatolic ordiaatolic bloodpressure.Theinddenea of

overalldrugralatadadvemaeventswaa30%withtheamlodipine regimen veraus14% withthe Ioaartenregimen(P=.014). The quaMy of life measurement of inventory of bothersome aymptoma demonatratad a difference betwean the Iosarten and ambditine regimen with regard tu edema: onty2% inthebaartan regimen and 12% in the amlodipineregimen (P =.01). In summafy, the Ioaartan regimen waa equaliy effaetiveviith the calciumchannd [email protected] However, with raapadto adverse avente, the Ioaartan regimen provfded batter toleratili paticularty with regard to edema and fawertherapy dropouts. Key Words: angiotenainII raceptor blocker, calcium btocker

Thomas D. Gilea, M.D., LataiaiaamStnte University Medical Center, New Orleans, LA Diabetesmeilitus is associatedwith macrovaecrdardisease (arfaerosclercsis), microveeeulardisease,and cardiomyopathy. In each of theseentitiea, the angiotensin[-converting errsyme (ACE) playa an importantml., particularly becauseACE is upragulatedin diabetes.31wIs,en increem in ACE WSUItSin increasedlocal concentrationsof angiotensinII and a decre-msa in concentrationsof bradykinin leading to increcsed thmmhogenicity,vesoconstriction,increasedgrowth of smoothmuscle,and alteration of myocardial compositionand function. Clinicadtrials have establishedthet ACE inhibitorsare effective in the managementof coronary atherosclerosisand its complications.Tbe ACE inhibitorsare not only effective in preventingheart feihrre following myocardial infarction (Ml), but they reducethe incidenceof recurrent Ml and decreasemortality in the post-Mf period when they ate administeredduring the acute episode.In the GISSI-3 trial, this benefit was particularly impressivein paticntawith diabetes. Diabetes elac is aaaociartad with cardiomyopathy,which incmaeaathe incidenceof heart failure and morbidity, particularly when accompaniedby eomnary atfaannclemsis and hypertension.ACE inhibitomfrmw beerseffective in heart faihm, both in the advancedand early stages.

Key Worda: ACE inhibitors,atherosclerosis, cardiomyopathy,diabeteamellitue, myocardial infimtion

Wednesday May 28, Ballroom C, 8:30 am Compliance With Antihypertensive Therapy: Pharmacology, Drug Development, Clinical Trials, Pharmacoeconomics, and Clinical Practice COMPLIANCE FROM

WITH

THEORY

Martha

N.

Baltimore,

Hill,

ANTIHYPERTENSIVE

THERAPY:

TO PRACTICE PhD.

Johns

Hopkins

University,

MO.

Petient compliance or adherenca to therapeutic recommendations is ona of tha major challenges in the management of high blood prassure. Traditionally, the problem has been defined as the extent to which petients fail to follow-through with racommandations and instructions. Guided by behavioral science theory, much has been learned about the roles of patiant knowledge, attitudes, beliefs, prior experiences, and resources including self-care skills and social support. Provider-patient communication and an activated patient have been shown to positively influence patient compliance. Recently, patient choice, decision making and control also have been shown to be important in shaping patients’ and providers’ expectations and bahavior. In addition, strategies to assist and reinforce physicians as they provide preventive services are most effective if congruent with haalth care organization policies. This presentation will review theoretical advances focusing on the multilevel nature of the compliance challenge. Factors at the patient, provider and health care organization levels will be reviewed. Emphesis will be placed on 1) integrating compliance issues in practice guidelines and clinical practice and 2) innovative strategies for augmenting the treating clinician: telephone and computer-assisted monitoring. KayWords:

243A