title: Antihypertensive efficacy and safety of manidipine versus amlodipine in elderly subjects with isolated systolic hypertension: MAISH study.
abstract: OBJECTIVE
  Isolated systolic hypertension (ISH) affects 10-20% of the elderly population and is strongly related to the risk of cardiovascular events. Elevated systolic BP values are primarily caused by reduced large vessel compliance with a consequent increase in total peripheral resistance. Vasodilating drugs, such as calcium channel antagonists, have proven to be effective in controlling ISH in elderly patients. This study set out to compare the antihypertensive efficacy and safety of two different calcium channel antagonists, manidipine and amlodipine, administered once daily in elderly subjects with ISH.
  
  
  METHODS
  In a European, randomised, double-blind, multicentre, parallel-group study, after a 2-week placebo run-in period, 195 patients aged >or=60 years with ISH received manidipine 10-20 mg once daily or amlodipine 5-10 mg once daily. Chlortalidone 25mg once daily could be added to the high dose of test drug in the event of insufficient antihypertensive control. The primary efficacy parameter was the proportion of patients with a reduction in office sitting systolic BP (SBP) >or=15 mm Hg, measured at trough, at the final visit. Secondary efficacy parameters included: the proportion of patients with a normal sitting SBP value (<140 mm Hg) at the final visit; a change from baseline to the final visit in mean office trough sitting SBP; a change from baseline to the final visit in the cardiovascular risk score as measured by the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) project score; the proportion of patients with at least a two-point reduction in the cardiovascular risk score; the percentage of patients requiring upward dose titration and diuretic add-on treatment and the investigator's final judgement. Safety and tolerability evaluations were based on adverse events, ECG and laboratory tests, and clinically relevant reports of abnormalities.
  
  
  RESULTS
  In the intention-to-treat population (n = 189), 76% and 72% of patients in the manidipine and amlodipine groups, respectively, had a reduction in sitting SBP of >or=15 mm Hg (p-value not significant for between-group comparison). The percentage of patients with a normal sitting SBP value was 52% in the manidipine group and 51% in the amlodipine group (p-value not significant for between-group comparison). Sitting SBP reductions at the end of treatment were -19.5 +/- 11.8 mm Hg in patients receiving manidipine and -18.4 +/- 11.1 mm Hg in patients receiving amlodipine. Both treatments induced a small reduction in cardiovascular risk score, with 45% of patients in both treatment groups having a two-point reduction in the final score. At the final visit, approximately half of the patients in both treatment groups were still being treated with the low dose of one of the test drugs (manidipine 10mg or amlodipine 5mg). Chlortalidone was added to the high dose of test drugs in 7% and 11% of patients in the amlodipine and manidipine groups, respectively. Both drugs were well tolerated, with a higher incidence of oedema in the amlodipine group (9% vs 4%). No clinically relevant changes in heart rate were induced by either treatment.
  
  
  CONCLUSIONS
  In elderly patients with ISH, treatment with manidipine for 12 weeks was well tolerated and effective and the antihypertensive effects obtained with manidipine were the same as those obtained with amlodipine.
authors: Hypertension Unit, Hospital Clinic (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors: Antonio Coca
authors: AC
authors: Payeras
authors: Krzysztof
authors: K
authors: Sladek
authors: Giuseppe
authors: G
authors: Lembo
authors: Marco
authors: M
authors: Alberici
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002752:Chlorthalidone / Q000627:therapeutic use; D004095:Dihydropyridines / Q000009:adverse effects / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009578:Nitrobenzenes; D010879:Piperazines; D018570:Risk Assessment; D012307:Risk Factors; D013599:Systole; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D009578:Nitrobenzenes; D010879:Piperazines; D017311:Amlodipine; C054218:manidipine; D002752:Chlorthalidone
references: Lancet. 1997 Sep 13;350(9080):757-64
references: 9297994
references: Br J Clin Pharmacol. 1993 May;35(5):499-505
references: 8512762
references: J Cardiovasc Pharmacol. 2001 Oct;38(4):642-50
references: 11588535
references: Clin Ther. 1992 Nov-Dec;14(6):813-20
references: 1286488
references: JAMA. 1991 Jun 26;265(24):3255-64
references: 2046107
references: J Hypertens. 2001 Feb;19(2):343-50
references: 11212979
references: J Hypertens. 1998 Dec;16(12 Pt 1):1823-9
references: 9869017
references: J Hypertens. 1999 Feb;17(2):151-83
references: 10067786
references: J Hypertens. 2000 Dec;18(12):1871-5
references: 11132613
references: Fundam Clin Pharmacol. 2002 Dec;16(6):537-44
references: 12685513
references: Drugs. 2004;64(17):1923-40
references: 15329044
references: J Hypertens. 2003 Jun;21(6):1011-53
references: 12777938
references: Arch Intern Med. 2002 Nov 11;162(20):2313-21
references: 12418945
references: Hypertension. 2001 Mar;37(3):869-74
references: 11244010
references: Clin Ther. 2003 May;25(5):1469-89
references: 12867222
references: Clin Ther. 2003 Nov;25(11):2765-80
references: 14693303
references: J Cardiovasc Pharmacol. 2000 Jun;35(6):926-31
references: 10836728
references: BMJ. 2001 Jul 14;323(7304):75-81
references: 11451781
references: Blood Press Monit. 2004 Apr;9(2):91-7
references: 15096906
references: Adv Ther. 2004 Nov-Dec;21(6):357-69
references: 15856859
references: Am J Hypertens. 1998 Jun;11(6 Pt 1):682-9
references: 9657627
references: Am Heart J. 1987 Jun;113(6):1489-94
references: 3591616
references: Arch Intern Med. 2000 Jan 24;160(2):211-20
references: 10647760
references: J Cardiovasc Pharmacol. 2005 Apr;45(4):310-3
references: 15772518
references: Am J Hypertens. 2002 Jan;15(1 Pt 1):31-6
references: 11824857
references: Eur Heart J. 1998 Jun;19 Suppl F:F27-31
references: 9651732
references: Eur J Clin Pharmacol. 2005 Aug;61(7):483-90
references: 16021438
references: Blood Press. 1998 Jul;7(4):197-207
references: 9858111
references: JAMA. 2003 May 21;289(19):2560-72
references: 12748199
references: Circulation. 1997 Jul 1;96(1):308-15
references: 9236450
references: Drugs Aging. 2003;20(4):277-86
references: 12641483
references: Cardiovasc Drugs Ther. 1999 May;13(3):243-8
references: 10439887