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New trends in combination therapy
SPECIAL SYMPOSIA
AJH-APRIL1996-VOL. 9, NO.4, PART 2
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach ADRENAL HYPERTENSION IN OLDER PATIENTS. R.G. Dluhy, Endocrine Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115. The clinical features of primary aldosteronism (PA) are nonspecific but are a consequence of the hypokalemic state. Neuromuscular symptoms, fatigue, and paresthesias are not uncommon; polyuria, nocturia and polydipsia probably result from hypokalemia-induced nephrogenic diabetes insipidus. Chronic hypokalemia can also impair insulin secretion and result in glucose intolerance. Resetting of the osmostat can occur in PA, as evidenced by slightly higher than normal serum sodium levels. This is a useful clinical point since a tendency toward a reduced serum sodium is seen in states of secondary aldosteronism. The hypertension associated with PA is usually moderate to severe with mean blood pressures (! SO) of 184 ! 28/112 ! 16 mmHg. Individuals with aldosterone-producing adenomas (APA) tend to have higher blood pressures than is seen in idiopathic hyperaldosteronism (IHA). The solitary APA is the most common cause of PA and accounts for approximately 65% of cases. IHA is the cause of PA in approximately 30% of cases. The aldosterone excess state produced in IHA is usually milder than in APA; as a result the biochemical abnormalities such as hypokalemia and suppression of plasma renin activity (PRA) are often less severe than those seen with APA. Compared to APA, IHA is seen in older individuals who usually have long-standing hypertension. Glucocorticoid-remediable Aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension of early onset that is usually severe and refractory to conventional anti-hypertensive therapies. Prospective screening of GRA pedigrees has surprisingly revealed that many affected individuals ~~~ W~r~~pokalemic and have variable blood pressures. Renin, aldosterone, hypokalemia, hypertension
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach Title: Qu.llly of Uf. Durinl Anlihyperlen.lv. T....tment: LotIOn. from the SHEP Study WIIII.m Applea.I•• M.D•• Vnlunlly ofT.nn...... Memphl. Thl••Iudy .... underl.ken a. pari of Ihe Sy.lolic Hyperlen.lon In the Eld.rly Proaram (SHEP) 10 delermln.lf low.rina.)oIolic blood prallure
In older penon. h.d any .d,ene '-'ORlIcquenca on
eoanillon, mood or Iel.ure .elk Itlt.. SHEP ..... multlcenl.r, double-hllnd. randoml7.ed, eonln,lIed Iri.I, ..llh .n .nr.a. followup ofOve )'..n. Parllelpan" .. llh l.ol.l.d .yololle hyperl.n.lon (ISH) "'ere r.ndomlz.d 10. ehlorlhalidon.1 .Ienolol"'alm.n or a malchlna pl.etbo. Th••nll... SHEP eohort (n....736) recelv.d P.rt I of Ih. h.ha, 101'.1 .,·.Iuliion Indudlna aloba' eoanltlon. d.p.....lve .ymplom., .nd ph, .1e.1 .nd ."dal funelionlna. SI. c1lnle.1 etnl.n .dmlnl.I....d Parillo Ihelr p.rtlelp.nl. (. .103-1) .1 b...llne .nd .nnu.lly. P.rtllneluded mo...."phl.lleal.d teol. of coanilive funellon. memor" problem-."I. Ina, qu.my of IIf•• anaer••nd lel.ure .cll.ltle•• Th.....ull. Indle.I.lh.1 .ctln t....tm.nt of ISH had no m.a.urable neaall.e eITed. and. for 10m. m•••u.......lIahl po.III•••ITed on cOlinIlion. ph).Ie.I••nd lel.u... runelk,n. All pOliti.. Ondinll' ....... In favor of Ih.I....lm.nt aroup bul ...... .mall. Th.... 'u. no .ITed on .ny m.a.u ......Ial.d to .mollon.1 .tale. In .ddillon. m•••ure. of eoanilive and emotlon.1 fundlon .......t.bl. In holh IIroup. for Ihe dur.tlon of the .Iudy. Bolh t
lment aroup
d. mode.ll nd t
.om. m•••u.... of phy.ieal.nd lel.u
rd d.lerlorallon
or
function over the .Iudy
p.mld. M.die.1 tre.lm.nIISH doe. nol ••u.e .ny d.l.rIor.llon of cOlinilion, .motional.tale, ph,.I••1fundlon, or lel.u....diville••
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach
Wednesday, May 15, Trianon Ballroom, 8:30 am Individualized Treatment of Hypertension in 1996
Individualized Selection of Anti-hypertensive Drug Therapy for Older Patients, Henry R. Black, M.D. Rush-Presbyterian-Sl Luke's Medical Center. Chicago. IL
NEW TRENDS IN COMBINATION THERAPY John M. Flack, Bowman Gray School of Medicine, Winston-Salem, NC Fewer than 50% of drug-treated hypertensives achieve blood pressure [BP] control to <140 /90 mmHg. Antihypertensive drug monotherapy typically results in BP normalization [<140 /90 mmHg] in no more than 50% to 60% of patients. Uptitration of drug doses improves BP control, albeit with an increase in the risk of side effects. This portends reduced patient compliance resulting in poor BP control, leading to increased risk of BP-related targetorgan complications such as stroke, renal insufficiency. congestive heart failure. and myocardial infarction. An advantage of combination drug therapy is greater BP reductions with fewer side effects compared to higher doses of either drug monotherapy. Combination therapy with diuretics and beta blockers or angiotensin converting enzyme [ACE] inhibitors is well accepted. More recent evidence suggests that combined vasodilator therapy [i.e., calcium antagonists plus an ACE inhibitor} represents potent and well tolerated BP lowering therapy Newer antihypertensive drug combinations, the efficacy and safety data supporting the combinations, and the theoretical advantages and disadvantages of such combinations will be discussed.
The approach to drug selection for treatment of hypertenslon In the elderly should vary little from What we do In younger Individuals. Initially we should select treatment based on the results of long tenm properly done randomized trials Which have assessed the efficacy of these agents to reduce morbidity and mortality and choose those that have been successful. But if there is a specific reason to favor a drug or drug class In a particular patient, we must use our clinical judgement and select that agent Instead. In the elderly. only regimens containing diuretics, usually In low dose (12.5-25 mg of HCTZ or Its equivalent with and without ~-sparlng diuretics) have reduced clinical events. Beta edrenoreceptor blockers do reduce blood pressure in the elderly but have not been successful in clinical trials. Other classes of agents also reduce blood pressure In this age group but have not as yet been adequately tested to determine Whether they will prevent clinical events as well or better than diuretics. although many such studies are in progress. In certain clinical situations, the choice of drugs for the elderly is clear, unless there is a compelling reason to favor another agenl Selecting diuretics for those with Isolated systolic hypertenslon; ACE Inhibitors for those with congestive heart failure; and alpha edrenoreceptor blockers for men with prostatism are just some examples. We mustn't forget that allhough choosing an anti-hypertensive for an elderly hypertensive may be more complex than In a younger Individual, treatment of hypertenslon in the elderly Is partiCUlarly effective at reducing morbidity and mortality and many fewer elderly need to be treated to prevent events than Is necessery In the younger hypertansives. Key words: Elderly, drug selection for hypertensives, diuretics, beta adrenoreceptor blockers, alpha adrenoreceptor blockers, ACE Inhibitors KeyWords:
KeyWords:
Combination, Drug Therapy, Hypertension
197A
AJH-APRIL1996-VOL. 9, NO.4, PART 2
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach ADRENAL HYPERTENSION IN OLDER PATIENTS. R.G. Dluhy, Endocrine Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115. The clinical features of primary aldosteronism (PA) are nonspecific but are a consequence of the hypokalemic state. Neuromuscular symptoms, fatigue, and paresthesias are not uncommon; polyuria, nocturia and polydipsia probably result from hypokalemia-induced nephrogenic diabetes insipidus. Chronic hypokalemia can also impair insulin secretion and result in glucose intolerance. Resetting of the osmostat can occur in PA, as evidenced by slightly higher than normal serum sodium levels. This is a useful clinical point since a tendency toward a reduced serum sodium is seen in states of secondary aldosteronism. The hypertension associated with PA is usually moderate to severe with mean blood pressures (! SO) of 184 ! 28/112 ! 16 mmHg. Individuals with aldosterone-producing adenomas (APA) tend to have higher blood pressures than is seen in idiopathic hyperaldosteronism (IHA). The solitary APA is the most common cause of PA and accounts for approximately 65% of cases. IHA is the cause of PA in approximately 30% of cases. The aldosterone excess state produced in IHA is usually milder than in APA; as a result the biochemical abnormalities such as hypokalemia and suppression of plasma renin activity (PRA) are often less severe than those seen with APA. Compared to APA, IHA is seen in older individuals who usually have long-standing hypertension. Glucocorticoid-remediable Aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension of early onset that is usually severe and refractory to conventional anti-hypertensive therapies. Prospective screening of GRA pedigrees has surprisingly revealed that many affected individuals ~~~ W~r~~pokalemic and have variable blood pressures. Renin, aldosterone, hypokalemia, hypertension
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach Title: Qu.llly of Uf. Durinl Anlihyperlen.lv. T....tment: LotIOn. from the SHEP Study WIIII.m Applea.I•• M.D•• Vnlunlly ofT.nn...... Memphl. Thl••Iudy .... underl.ken a. pari of Ihe Sy.lolic Hyperlen.lon In the Eld.rly Proaram (SHEP) 10 delermln.lf low.rina.)oIolic blood prallure
In older penon. h.d any .d,ene '-'ORlIcquenca on
eoanillon, mood or Iel.ure .elk Itlt.. SHEP ..... multlcenl.r, double-hllnd. randoml7.ed, eonln,lIed Iri.I, ..llh .n .nr.a. followup ofOve )'..n. Parllelpan" .. llh l.ol.l.d .yololle hyperl.n.lon (ISH) "'ere r.ndomlz.d 10. ehlorlhalidon.1 .Ienolol"'alm.n or a malchlna pl.etbo. Th••nll... SHEP eohort (n....736) recelv.d P.rt I of Ih. h.ha, 101'.1 .,·.Iuliion Indudlna aloba' eoanltlon. d.p.....lve .ymplom., .nd ph, .1e.1 .nd ."dal funelionlna. SI. c1lnle.1 etnl.n .dmlnl.I....d Parillo Ihelr p.rtlelp.nl. (. .103-1) .1 b...llne .nd .nnu.lly. P.rtllneluded mo...."phl.lleal.d teol. of coanilive funellon. memor" problem-."I. Ina, qu.my of IIf•• anaer••nd lel.ure .cll.ltle•• Th.....ull. Indle.I.lh.1 .ctln t....tm.nt of ISH had no m.a.urable neaall.e eITed. and. for 10m. m•••u.......lIahl po.III•••ITed on cOlinIlion. ph).Ie.I••nd lel.u... runelk,n. All pOliti.. Ondinll' ....... In favor of Ih.I....lm.nt aroup bul ...... .mall. Th.... 'u. no .ITed on .ny m.a.u ......Ial.d to .mollon.1 .tale. In .ddillon. m•••ure. of eoanilive and emotlon.1 fundlon .......t.bl. In holh IIroup. for Ihe dur.tlon of the .Iudy. Bolh t
lment aroup
d. mode.ll nd t
.om. m•••u.... of phy.ieal.nd lel.u
rd d.lerlorallon
or
function over the .Iudy
p.mld. M.die.1 tre.lm.nIISH doe. nol ••u.e .ny d.l.rIor.llon of cOlinilion, .motional.tale, ph,.I••1fundlon, or lel.u....diville••
Wednesday, May 15, Mercury Ballroom, 8:30 am Hypertension in the Elderly: A Comprehensive Approach
Wednesday, May 15, Trianon Ballroom, 8:30 am Individualized Treatment of Hypertension in 1996
Individualized Selection of Anti-hypertensive Drug Therapy for Older Patients, Henry R. Black, M.D. Rush-Presbyterian-Sl Luke's Medical Center. Chicago. IL
NEW TRENDS IN COMBINATION THERAPY John M. Flack, Bowman Gray School of Medicine, Winston-Salem, NC Fewer than 50% of drug-treated hypertensives achieve blood pressure [BP] control to <140 /90 mmHg. Antihypertensive drug monotherapy typically results in BP normalization [<140 /90 mmHg] in no more than 50% to 60% of patients. Uptitration of drug doses improves BP control, albeit with an increase in the risk of side effects. This portends reduced patient compliance resulting in poor BP control, leading to increased risk of BP-related targetorgan complications such as stroke, renal insufficiency. congestive heart failure. and myocardial infarction. An advantage of combination drug therapy is greater BP reductions with fewer side effects compared to higher doses of either drug monotherapy. Combination therapy with diuretics and beta blockers or angiotensin converting enzyme [ACE] inhibitors is well accepted. More recent evidence suggests that combined vasodilator therapy [i.e., calcium antagonists plus an ACE inhibitor} represents potent and well tolerated BP lowering therapy Newer antihypertensive drug combinations, the efficacy and safety data supporting the combinations, and the theoretical advantages and disadvantages of such combinations will be discussed.
The approach to drug selection for treatment of hypertenslon In the elderly should vary little from What we do In younger Individuals. Initially we should select treatment based on the results of long tenm properly done randomized trials Which have assessed the efficacy of these agents to reduce morbidity and mortality and choose those that have been successful. But if there is a specific reason to favor a drug or drug class In a particular patient, we must use our clinical judgement and select that agent Instead. In the elderly. only regimens containing diuretics, usually In low dose (12.5-25 mg of HCTZ or Its equivalent with and without ~-sparlng diuretics) have reduced clinical events. Beta edrenoreceptor blockers do reduce blood pressure in the elderly but have not been successful in clinical trials. Other classes of agents also reduce blood pressure In this age group but have not as yet been adequately tested to determine Whether they will prevent clinical events as well or better than diuretics. although many such studies are in progress. In certain clinical situations, the choice of drugs for the elderly is clear, unless there is a compelling reason to favor another agenl Selecting diuretics for those with Isolated systolic hypertenslon; ACE Inhibitors for those with congestive heart failure; and alpha edrenoreceptor blockers for men with prostatism are just some examples. We mustn't forget that allhough choosing an anti-hypertensive for an elderly hypertensive may be more complex than In a younger Individual, treatment of hypertenslon in the elderly Is partiCUlarly effective at reducing morbidity and mortality and many fewer elderly need to be treated to prevent events than Is necessery In the younger hypertansives. Key words: Elderly, drug selection for hypertensives, diuretics, beta adrenoreceptor blockers, alpha adrenoreceptor blockers, ACE Inhibitors KeyWords:
KeyWords:
Combination, Drug Therapy, Hypertension
197A