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Use of Angiotensin (AII) antagonist losartan in patient treated with DSC LDL-apheresis.
134A
ASH
AJH-APRIL 1999-VOL. 12, NO. 4, PART 2
XIV ABSTRACTS
D092
D093
1NDOMETHACIN DOES NOT INCREASE BP IN HYPERTENSIVE PATIENTS TREATED WITH AMLODIPINE T. Morgan*, A. Anderson, D. Bertram and E. Jones, Hypertension Clinic, ARMC, Heidelberg, AustraLia Arthritis is relatively common in older hypertensive patients and they require non steroidal anti-inflammatory drags (NSAID). This may lead to loss of hypertensive control due in part to sodium retention. Dihydropyridine calcium channel blocking drugs' effects are relatively independent of sodium status and NSAID may not have this adverse effect in people treated with amlodipine. Twentythree patients (IgM, 5F) age 60-80 (mean 69y) with essential hypertension well controlled on amledipine (5 or 10 mg/d) completed a double blind, crossover study comparing the effect of placebo or indomcthacin (50 mg twice daily) over a 3 week period on BP. BP was measured at the clinic (24 hours post dose) and by ambulatory BP monitoring for 27 hours. At the end of the double blind placebo period clinic BP was 153 ± 3/81 ± 1.5 mmHg and at the end of the indomethacin period 156 ± 3/82 ± 19 mmHg (n = 23, p >0.2). The mean 24 hour BP on placebo was 141 ± 2/76.8 ± 1.4 and on indomethacin was 142 ±2/77.2 ± 1.2 (n = 23, p >0.4). There were no differences in daytime, night time or early morning BP (see Table). The power to detect a difference of 2 mmHg or more was 95% Blood Pressurre mmHg Placebo lndomethacin Sys Diast Sys Diast p 24h mean 141±2 76.8±1.4 142±2 77.2±1.2 >0.4 day mean 143±2 78.4_+1.4 145±2 79.3±1.3 >0.3 night mean 128±3 67.5±1.8 130±3 67.6±1.2 >0.4 morning mean 149±3 82.2_+1.7 149±3 81.5±1.7 >0.8 Weight rose by 0.64 ± 0.28 Kg (p < 0.05). Plasma renin and aldosterone were not altered. lndomethaein can be given to people controlled on amlodipine without causing a rise in BP and is a preferred treatment for hypertensive patients with associated arthritis. Key Words: Arthritis; Ca Antagonists; Amlodipine; lndomethacin; Hypertension
BETA B L O C K E R S A N D SERUM POTASSIUM LEVELS IN H E M O D I A L Y S I S PATIENTS. R W Dunlay* and .IT Frock, Creighton University, Omaha, NE. Beta blockers (BB) are c o m m o n l y prescribed for hypertension and have been shown to improve survival after myocardial infarction. Many nephrologists have been reluctant to use BB in hemodialysis patients, since BB may decrease the cellular uptake of potassium (K) and might be associated with hyperkalemia (HK). The purpose of this study was to see if the use of BB was associated with a change in the serum K level in stable hemodialysis patients. The records of all patients on hemodialysis for at least three months with K measurements each month during that period were examined. 121 patients met criteria f o r s t u d y entry. 83 patients who were not receiving BB (BB-) were compared with 38 patients who were taking BB (BB+). The was no significant difference (NSD) in the ages of patients, B B - 56.3 ± 16.1 years vs.BB+ 53.8 ± 13.7
D094
D095
THE E F F I C A C Y A N D S A F E T Y O F I R B E S A R T A N IN PATIENTS W I T H E S S E N T I A L H Y P E R T E N S I O N IN C O M M U N I T Y H O S P I T A L S OF C A T A L O N I A N . A. FeUp, J, Sobrino*, J. Plana, J. Soter, L. Ribera, M J. Add~n, J. Mbdol, A Minguez, J. Esqud, M Pladevall, L Comas, M, Cases, J. Closes, J Rema, /~ Coca*. Hypertension Research Foundation of the Catalan Community Hospitals (FEHTACC), Barcelona, Spain. The aim of the study was to analyze the efficacy and safety of irbesertan (IBST) during 12 weeks in monotherapy or associated to other antihypetlensive drugs, Two-hundred four patients (93 males, 111 females), mean age 5 7 8 + 123 years, with not ¢ontrolisd essential hypertension with conventional antihypertsr~ive monotherapy (diuretics, ~blockers, calcium channel blockers (CCB), ACE*inhibitors, *z-blockers), IBST 150 mg was added or in case of secondary effects or null answer the previous drug was suspended this one and began IBST in monotherapy regime. After 6 weeks if were not obtained to an optimal control of BP (BP < 140/90 mmHg) was irmressed to the 300 mg dose of IBST and proced and it was come to a new control after 6 weeks. Onehundred ninety nine patients completed the study, 7 left by adverse events and 4 by lost of follow up, 76 patients were treated ~ IBST in monotherapy and 117 patients ~ IBST and another antihypartsnsive drug, diuretics in 19 patients, ~-blockers in 19 patients, CCB in 39 patients, ACE-inhibitors in 25 patients and co-blockers in 15 patients. An optimal control of the BP was obtained in 99 patients (51,3%). There was no significant difference between the group of patients treated in monotherapy (49,3%) and the group of patients dealt with IBST and another drug (52,5%). The rate of responders (defined by a % of patients who reduces the DBP > 5 mmHg) was of 91,7% (177 patients), 66 patients (88%) of the monotherapy group and 111 patients (94%) of the association group. A signif'mant reducl~on of the SBP es of the DBP the 6 weeks and at the end of the study was observed. There was no statistically significant or clinically relevant difference in reduction of mean of BP when comperirt~l different ~lroups.
USE OF ANGIOTENSIN (All) ANTAGONIST L O S A R T A N IN PATIENT T R E A T E D WITH DSC LDLAPHERESIS. *Maxis P +Pintus S, *Bianco A, +Pintus P, *Sanna A. *Department o f Cardiology +Centre for Metabolic Diseases, Ospedale G. Brotzu, Cagliari, Italy
I
170,9~19,1 ~16,5~¢10.3 191,9~¢19,7 66,1i9,9 144,9.15,1 849~=9.1 iB~r+clume¢ 172,9±19.0 100.3=19.5 162.4~21.7 91,4,14,9 146,9=17.0 85,3~9.9 1 iBsr*C.uod~r 166.3,17.8 102,2,7,4 166,7,20.9 92.9*7.7 145.9t19.1 g0.4,8,9 I~r*AcE 177.2±19.9 g8.2,19.5 197.1,19.8 88,2,12.9 154.4,21.4 87.2±13.3 ~B,~r÷CCB 170.8=19.9 96.5±9.8 151.2¢15.5 66,3±11.9 144±13.6 66.9,7.2 I IBSr+=-bbcamr 166,8,17.8 g6.4,9.3 149.9*12.3 88.9,5.3 140.2,11.9 83.5¢8.2 In conclusion, irbesartln w a s well tolerated. A n optimal degree of control of BP w a s obtained in more than a half of the studied patients and a rate of armwer in 90 % patients. This effec~veness is similar w h e n it w a s administered in monotherapy like in association. in,s'r
Key Words:
Irbesartsn, hypertension
years. The serum K for the BB- group was 5.0 ± 0.8 meq/L compared with 5.1 - 0.7 meq/L in the BB+ group (NSD). The number of patients experiencing serious HK, defined as a serum K > 6.5 meq/L was examined. There was a trend toward more episodes of serious HK in the BB+ group, with 15% (6/38) of BB+ patients experiencing serious HK compared with 7% (6/83) of BB- patients (p=.06). Four of the BB- patients had a serum K > 7.0 meq/L, including two with a life threatening K > 8.0 meq/L. T w o of the BB+ patients had a serum K > 7.0 meq/L and none had a K >8.0 meq/L. W e conclude that BB therapy may be safely used in hemodialysis patients, with only a minority experiencing serious HK.
Key Words:
potassium, beta blocker, hyperkalemia, hemodialysis
Angiotensin-converting-enzyme (ACE) inhibitors reduce morbidity and mortality in patients with chronic hearth failure and systolic lefl-ventricular disorder as well as in patients who have had a myocardial infarction. These drugs, in familial hypercbolesterolemic (FH) patients treated with low density lipoprotein (LDL) apheresis using dextran sulfate-cellulose (DSC) columns, can cause marked hypotensive crises. These reactions were probably triggered by elevated generation of bradykinin due to contact of blood with polyanionic DSC (a potent activator of the contact activating system o f coagulation factors), and bradykinin's diminished inactivation due to ACE inhibitors. These adverse reactions are called anion-blood contact reaction (ABC reaction). Losartan is the first of a new class of drugs called angiotensin (All)-amagonists. This drug acts blocking selectively the AT1 receptor and preventing the linking of All to the site of action. Two FH patients affected by CHD, in therapy with DSCLDL apheresis, who in past years experienced ABC reaction during treatment with enalapril, have been treated with Losartan (Neolotan, Neopharmed, Rome, Italy) 50 mg, 1 tablet once a day. No symptoms of hypotension, flushing, dyspnoea or bradycardia have been referred during and after apheresis treatment. In conclusion these data confirm the mechanism of the ABC reaction due to ACE-inhibitors. Furthermore losartan seems to be well tolerated in FH patients affected by CHD and it permits to by-pass the problems inherent the use of conventional inhibitors of ACE in patients treated with LDL-apheresis with DSC columns. Key Words:
Angiotensin, LDL-Apheresis, Losartan
ASH
AJH-APRIL 1999-VOL. 12, NO. 4, PART 2
XIV ABSTRACTS
D092
D093
1NDOMETHACIN DOES NOT INCREASE BP IN HYPERTENSIVE PATIENTS TREATED WITH AMLODIPINE T. Morgan*, A. Anderson, D. Bertram and E. Jones, Hypertension Clinic, ARMC, Heidelberg, AustraLia Arthritis is relatively common in older hypertensive patients and they require non steroidal anti-inflammatory drags (NSAID). This may lead to loss of hypertensive control due in part to sodium retention. Dihydropyridine calcium channel blocking drugs' effects are relatively independent of sodium status and NSAID may not have this adverse effect in people treated with amlodipine. Twentythree patients (IgM, 5F) age 60-80 (mean 69y) with essential hypertension well controlled on amledipine (5 or 10 mg/d) completed a double blind, crossover study comparing the effect of placebo or indomcthacin (50 mg twice daily) over a 3 week period on BP. BP was measured at the clinic (24 hours post dose) and by ambulatory BP monitoring for 27 hours. At the end of the double blind placebo period clinic BP was 153 ± 3/81 ± 1.5 mmHg and at the end of the indomethacin period 156 ± 3/82 ± 19 mmHg (n = 23, p >0.2). The mean 24 hour BP on placebo was 141 ± 2/76.8 ± 1.4 and on indomethacin was 142 ±2/77.2 ± 1.2 (n = 23, p >0.4). There were no differences in daytime, night time or early morning BP (see Table). The power to detect a difference of 2 mmHg or more was 95% Blood Pressurre mmHg Placebo lndomethacin Sys Diast Sys Diast p 24h mean 141±2 76.8±1.4 142±2 77.2±1.2 >0.4 day mean 143±2 78.4_+1.4 145±2 79.3±1.3 >0.3 night mean 128±3 67.5±1.8 130±3 67.6±1.2 >0.4 morning mean 149±3 82.2_+1.7 149±3 81.5±1.7 >0.8 Weight rose by 0.64 ± 0.28 Kg (p < 0.05). Plasma renin and aldosterone were not altered. lndomethaein can be given to people controlled on amlodipine without causing a rise in BP and is a preferred treatment for hypertensive patients with associated arthritis. Key Words: Arthritis; Ca Antagonists; Amlodipine; lndomethacin; Hypertension
BETA B L O C K E R S A N D SERUM POTASSIUM LEVELS IN H E M O D I A L Y S I S PATIENTS. R W Dunlay* and .IT Frock, Creighton University, Omaha, NE. Beta blockers (BB) are c o m m o n l y prescribed for hypertension and have been shown to improve survival after myocardial infarction. Many nephrologists have been reluctant to use BB in hemodialysis patients, since BB may decrease the cellular uptake of potassium (K) and might be associated with hyperkalemia (HK). The purpose of this study was to see if the use of BB was associated with a change in the serum K level in stable hemodialysis patients. The records of all patients on hemodialysis for at least three months with K measurements each month during that period were examined. 121 patients met criteria f o r s t u d y entry. 83 patients who were not receiving BB (BB-) were compared with 38 patients who were taking BB (BB+). The was no significant difference (NSD) in the ages of patients, B B - 56.3 ± 16.1 years vs.BB+ 53.8 ± 13.7
D094
D095
THE E F F I C A C Y A N D S A F E T Y O F I R B E S A R T A N IN PATIENTS W I T H E S S E N T I A L H Y P E R T E N S I O N IN C O M M U N I T Y H O S P I T A L S OF C A T A L O N I A N . A. FeUp, J, Sobrino*, J. Plana, J. Soter, L. Ribera, M J. Add~n, J. Mbdol, A Minguez, J. Esqud, M Pladevall, L Comas, M, Cases, J. Closes, J Rema, /~ Coca*. Hypertension Research Foundation of the Catalan Community Hospitals (FEHTACC), Barcelona, Spain. The aim of the study was to analyze the efficacy and safety of irbesertan (IBST) during 12 weeks in monotherapy or associated to other antihypetlensive drugs, Two-hundred four patients (93 males, 111 females), mean age 5 7 8 + 123 years, with not ¢ontrolisd essential hypertension with conventional antihypertsr~ive monotherapy (diuretics, ~blockers, calcium channel blockers (CCB), ACE*inhibitors, *z-blockers), IBST 150 mg was added or in case of secondary effects or null answer the previous drug was suspended this one and began IBST in monotherapy regime. After 6 weeks if were not obtained to an optimal control of BP (BP < 140/90 mmHg) was irmressed to the 300 mg dose of IBST and proced and it was come to a new control after 6 weeks. Onehundred ninety nine patients completed the study, 7 left by adverse events and 4 by lost of follow up, 76 patients were treated ~ IBST in monotherapy and 117 patients ~ IBST and another antihypartsnsive drug, diuretics in 19 patients, ~-blockers in 19 patients, CCB in 39 patients, ACE-inhibitors in 25 patients and co-blockers in 15 patients. An optimal control of the BP was obtained in 99 patients (51,3%). There was no significant difference between the group of patients treated in monotherapy (49,3%) and the group of patients dealt with IBST and another drug (52,5%). The rate of responders (defined by a % of patients who reduces the DBP > 5 mmHg) was of 91,7% (177 patients), 66 patients (88%) of the monotherapy group and 111 patients (94%) of the association group. A signif'mant reducl~on of the SBP es of the DBP the 6 weeks and at the end of the study was observed. There was no statistically significant or clinically relevant difference in reduction of mean of BP when comperirt~l different ~lroups.
USE OF ANGIOTENSIN (All) ANTAGONIST L O S A R T A N IN PATIENT T R E A T E D WITH DSC LDLAPHERESIS. *Maxis P +Pintus S, *Bianco A, +Pintus P, *Sanna A. *Department o f Cardiology +Centre for Metabolic Diseases, Ospedale G. Brotzu, Cagliari, Italy
I
170,9~19,1 ~16,5~¢10.3 191,9~¢19,7 66,1i9,9 144,9.15,1 849~=9.1 iB~r+clume¢ 172,9±19.0 100.3=19.5 162.4~21.7 91,4,14,9 146,9=17.0 85,3~9.9 1 iBsr*C.uod~r 166.3,17.8 102,2,7,4 166,7,20.9 92.9*7.7 145.9t19.1 g0.4,8,9 I~r*AcE 177.2±19.9 g8.2,19.5 197.1,19.8 88,2,12.9 154.4,21.4 87.2±13.3 ~B,~r÷CCB 170.8=19.9 96.5±9.8 151.2¢15.5 66,3±11.9 144±13.6 66.9,7.2 I IBSr+=-bbcamr 166,8,17.8 g6.4,9.3 149.9*12.3 88.9,5.3 140.2,11.9 83.5¢8.2 In conclusion, irbesartln w a s well tolerated. A n optimal degree of control of BP w a s obtained in more than a half of the studied patients and a rate of armwer in 90 % patients. This effec~veness is similar w h e n it w a s administered in monotherapy like in association. in,s'r
Key Words:
Irbesartsn, hypertension
years. The serum K for the BB- group was 5.0 ± 0.8 meq/L compared with 5.1 - 0.7 meq/L in the BB+ group (NSD). The number of patients experiencing serious HK, defined as a serum K > 6.5 meq/L was examined. There was a trend toward more episodes of serious HK in the BB+ group, with 15% (6/38) of BB+ patients experiencing serious HK compared with 7% (6/83) of BB- patients (p=.06). Four of the BB- patients had a serum K > 7.0 meq/L, including two with a life threatening K > 8.0 meq/L. T w o of the BB+ patients had a serum K > 7.0 meq/L and none had a K >8.0 meq/L. W e conclude that BB therapy may be safely used in hemodialysis patients, with only a minority experiencing serious HK.
Key Words:
potassium, beta blocker, hyperkalemia, hemodialysis
Angiotensin-converting-enzyme (ACE) inhibitors reduce morbidity and mortality in patients with chronic hearth failure and systolic lefl-ventricular disorder as well as in patients who have had a myocardial infarction. These drugs, in familial hypercbolesterolemic (FH) patients treated with low density lipoprotein (LDL) apheresis using dextran sulfate-cellulose (DSC) columns, can cause marked hypotensive crises. These reactions were probably triggered by elevated generation of bradykinin due to contact of blood with polyanionic DSC (a potent activator of the contact activating system o f coagulation factors), and bradykinin's diminished inactivation due to ACE inhibitors. These adverse reactions are called anion-blood contact reaction (ABC reaction). Losartan is the first of a new class of drugs called angiotensin (All)-amagonists. This drug acts blocking selectively the AT1 receptor and preventing the linking of All to the site of action. Two FH patients affected by CHD, in therapy with DSCLDL apheresis, who in past years experienced ABC reaction during treatment with enalapril, have been treated with Losartan (Neolotan, Neopharmed, Rome, Italy) 50 mg, 1 tablet once a day. No symptoms of hypotension, flushing, dyspnoea or bradycardia have been referred during and after apheresis treatment. In conclusion these data confirm the mechanism of the ABC reaction due to ACE-inhibitors. Furthermore losartan seems to be well tolerated in FH patients affected by CHD and it permits to by-pass the problems inherent the use of conventional inhibitors of ACE in patients treated with LDL-apheresis with DSC columns. Key Words:
Angiotensin, LDL-Apheresis, Losartan