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Trials
Published in: Trials 1/2006

Open Access 01-12-2006 | Study protocol

Fracture risk and the use of a diuretic (indapamide sr) ± perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET)

Authors: Christopher J Bulpitt, Ruth Peters, Jan A Staessen, Lutgarde Thijs, Marie-Christine De Vernejoul, Astrid E Fletcher, Nigel S Beckett

Published in: Trials | Issue 1/2006

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Abstract

Background

The Hypertension in the Very Elderly Trial (HYVET) is a placebo controlled double blind trial of treating hypertension with indapamide Slow Release (SR) ± perindopril in subjects over the age of 80 years. The primary endpoints are stroke (fatal and non fatal). In view of the fact that thiazide diuretics and indapamide reduce urinary calcium and may increase bone mineral density, a fracture sub study was designed to investigate whether or not the trial anti-hypertensive treatment will reduce the fracture rate in very elderly hypertensive subjects.

Methods

In the trial considerable care is taken to ascertain any fractures and to identify risk factors for fracture, such as falls, co-morbidity, drug treatment, smoking and drinking habits, levels of activity, biochemical abnormalities, cardiac irregularities, impaired cognitive function and symptoms of orthostatic hypotension.

Potential results

The trial is expected to provide 10,500 patient years of follow-up. Given a fracture rate of 40/1000 patient years and a 20% difference in fracture rate, the power of the sub study is 58% to detect this difference at the 5% level of significance. The corresponding power for a reduction of 25% is 78%.

Conclusion

The trial is well under way, expected to complete in 2009, and on target to detect, if present, the above differences in fracture rate.
Literature
1.
Melton LJ, Crowson CS, Khosla S, Wilson DM, O'Fallon WM: Fracture risk among patients with urolithiasis: a population based cohort study. Kidney Int. 1998, 53: 459-464. 10.1046/j.1523-1755.1998.00779.x.CrossRefPubMed
2.
Lawoyin S, Sismilich S, Browne R, Pak CY: Bone mineral content in patients with calcium urolithiasis. Metabolism. 1979, 28: 1250-1254. 10.1016/0026-0495(79)90139-2.CrossRefPubMed
3.
Malluche HH, Tschoepe W, Ritz E, Meyer-Sabellek W, Massry SG: Abnormal bone histology in idiopathic hypercalciuria. J Clin Endocrinol Metab. 1980, 50: 654-8.CrossRefPubMed
4.
Cappuccio FP, Strazzullo P, Mancini M: Kidney stones and hypertension: population based study of an independent clinical association. BMJ. 1990, 300: 1234-6.CrossRefPubMedPubMedCentral
5.
Robertson WG, Peacock M, Baker M: Epidemiological studies on urinary stone disease in men in Leeds. Fortsch Urol Nephrol. 1984, 22: 27-32.CrossRef
6.
Nijenhuis T, Vallon V, van der Kemp AW, Loffing J, Hoenderop JG, Bindels RJ: Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest. 2005, 115: 1651-8. 10.1172/JCI24134.CrossRefPubMedPubMedCentral
7.
Scholz D, Schwille PO, Sigel A: Double-blind study with thiazide in recurrent calcium lithiasis. J Urol. 1982, 128: 903-7.PubMed
8.
Nijenhuis T, Hoenderop JG, Loffing J, van der Kemp AW, van Os CH, Bindels RJ: Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int. 2003, 64: 555-64. 10.1046/j.1523-1755.2003.00128.x.CrossRefPubMed
9.
Laerum E, Larsen S: Thiazide prophylaxis of urolithiasis. Arch Med Scand. 1984, 215: 383-9.
10.
Robertson WG, Peacock M, Selby PL, Williams RE, Clark P, Chisholm GD, Hargreaves TB, Rose MB, Wilkinson H: A multicentre trial to evaluate three treatments for recurrent idiopathic calcium stone disease – a preliminary report. Urolithiasis and related clinical research. Edited by: Schwille PO, Smith LH, Robertson WG, Vahlensieck W. 1985, New York: Plenum Press, 545-8.CrossRef
11.
Ettinger B, Citron JT, Tang A, Livermore B: Prophylaxis of calcium oxalate stones:clinical trials of allopurinol magnesium hydroxide and chlorthalidone. Urolithiasis and related clinical research. Edited by: Schwille PO, Smith LH, Robertson WG, Vahlensieck W. 1985, New york: Plenum Press, 549-52.CrossRef
12.
Brocks P, Dahl C, Wolf H, Transnbol I: Do thiazides prevent recurrent idiopathic renal calcium stones?. Lancet. 1981, 2: 124-5. 10.1016/S0140-6736(81)90302-0.CrossRefPubMed
13.
14.
Borghi L, Elia G, Trapassi MR, Melloni E, Amato F, Barbarese F, Novarini A: Acute effect of indapamide on urine calcium excretion in nephrolithiasis and human essential hypertension. Pharmacology. 1988, 36: 348-55.CrossRefPubMed
15.
Borghi L, Meschi T, Guerra A, Novarini A: Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences. J Cardiovasc Pharmacol. 1993, 22 (Suppl 6): S78-86.CrossRefPubMed
16.
Ceylan K, Topal C, Erkoc R, Sayarlioglu H, Can S, Yilmaz Y, Dogan E, Algun E, Gonulalan H: Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease. Ann Pharmacother. 2005, 39: 1034-8. 10.1345/aph.1E544.CrossRefPubMed
17.
Danielson H, Pedersen EB, Spencer ED: Effect of indapamide on the renin-aldosterone system, and urinary excretion of potassium and calcium in essential hypertension. Br J Clin Pharmacol. 1984, 18: 229-31.CrossRef
18.
Lalande A, Roux S, Denne MA, Stanley ER, Schiavi P, Guez D, De Vernejoul MC: Indapamide, a thiazide-like diuretic, decreases bone resorption in vitro. J Bone Miner Res. 2001, 16: 361-70. 10.1359/jbmr.2001.16.2.361.CrossRefPubMed
19.
LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE: Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized double-blind, placebo-controlled trial. Ann Intern Med. 2000, 133: 516-526.CrossRefPubMed
20.
Reid IR, Ames RW, Orr-Walker BJ, Clearwater JM, Horne Am, Evans MC, Murray MAF, McNeil AR, Gamble GD: Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomised controlled trial. Am J Med. 2000, 109: 362-370. 10.1016/S0002-9343(00)00510-6.CrossRefPubMed
21.
Schlienger KG, Kraenzlin ME, Jick SS, Meier CR: Use of beta-blockers and risk of fractures. JAMA. 2004, 292: 1326-32. 10.1001/jama.292.11.1326.CrossRefPubMed
22.
Rejnmark L, Vestergaard P, Mosckilde L: Reduced fractures risk in users of thiazide diuretics. Calif Tissue Int. 2005, 76: 167-75. 10.1007/s00223-004-0084-2.CrossRef
23.
Schoofs MW, van der Klift M, Hofman A, de Laet CE, Herings RM, Stijnen T, Pols HA, Stricker BH: Thiazide diuretics and the risk for hip fracture. Ann Intern Med. 139 (6): 476-82. 2003 Sep 16
24.
Feskannich D, Willett WC, Stampfer MJ, Colditz GA: A prospective study of thiazide use and fractures in women. Osteoporos Int. 1997, 7: 79-84. 10.1007/BF01623465.CrossRef
25.
Cauley JA, Fullman RL, Stone KL, Zmuda JM, Bauer DC, Barrett-Connor E, Ensrud K, Lau EM, Orwell ES, for the Mr. OS Research Group: Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int. 2055, 12: 1525-37.
26.
Jones G, Nguyen T, Sambrook PN, Eisman JA: Thiazide diuretics and fractures: can meta-analysis help?. J Bone Miner Res. 1995, 10: 106-111.PubMed
27.
Timio F, Kerry SM, Anson KM, Eastwood JB, Cappucio FP: Calcium urolithiasis blood pressure and salt intake. Blood Press. 2003, 12: 122-7. 10.1080/08037050310001084.CrossRefPubMed
28.
Bulpitt CJ, Fletcher AE, Beckett N, Coope J, Gil-Extremera B, Forette F, Nachev C, Potter J, Sever P, Staessen J, Swift C, Tuomilehto J: Hypertension in the Very Elderly Trial (HYVET) Protocol for main trial. Drugs Aging. 2001, 18: 151-164. 10.2165/00002512-200118030-00001.CrossRefPubMed
29.
Landi F, Onder G, Cesari M, Barillaro C, Russo A, Bernabei R: Silver Network Home Care Study Group. Psychotropic medications and risk for falls among community-dwelling frail older people: an observational study. J Gerontol A Biol Sci Med Sci. 2005, 60: 622-6.CrossRefPubMed
30.
Kallin K, Gustafson Y, Sandman PO, Karlsson S: Drugs and Falls in older people in geriatric care settings. Aging Clin Exp Res. 2004, 16: 270-6.CrossRefPubMed
31.
Kinjo M, Setoguchi S, Schneeweiss S, Soloman DH: Bone mineral density in subjects using central nervous system-active medications. Am J Med. 2005, 118: 1414-10.1016/j.amjmed.2005.07.033.CrossRefPubMed
32.
Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G: Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006, 119: 71el-8. 10.1016/j.amjmed.2005.09.026.CrossRef
33.
Rait G, Fletcher A, Smeeth L, Brayne C, Stirling S, Nunes M, Breeze E, Siu-Woon Ng E, Bulpitt CJ, Jones D, Tulloch AJ: Prevalence of cognitive impairment: results from the MRC trial of assessment and management of older people in the community. Age and Ageing. 2005, 35: 242-248. 10.1093/ageing/afi039.CrossRef
34.
Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H: Validation of a short orientation-memory-concentration test of cognitive impairment. American Journal Psychiatry. 1983, 140: 734-738.CrossRef
35.
Folstein W, Folstein SE, Mc Hugh RP, "Mini Mental State": A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research. 1975, 12: 189-198. 10.1016/0022-3956(75)90026-6.CrossRefPubMed
36.
Spreen O, Strauss E: A Compendium of Neuropsychological Tests: Administration, Norms and Commentary. 1998, Oxford: Oxford University Press, 2
37.
Almeida O, Almeida S: Short versions of the Geriatric Depression Scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. International Journal of Geriatric Psychiatry. 1999, 14: 858-865. 10.1002/(SICI)1099-1166(199910)14:10<858::AID-GPS35>3.0.CO;2-8.CrossRefPubMed
38.
Maravic M, Le Bihan C, Landais P, Fardellone P: Incidence and cost of osteoporotic fractures in France during 2001. A methodological approach by the national hospital database. Osteoporos Int. 2005, 16: 1475-1480. 10.1007/s00198-005-2031-0.CrossRefPubMed
39.
Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA: Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study Bone. 2004, 34 (1): 195-202.
40.
Giverson IM: Time trends of age-adjusted incidence rates of first hip fractures: a register-based study among older people in Viborg County, Denmark, 1987–1997. Osteoporos Int. 2006, 12: 1-13.
41.
Leil Y, Castel H, Alkalay D: Marked secular increase in the incidence rates of osteoporotic hip fractures in women and men in southern Israel. Isr Med Assoc J. 2005, 7: 708-11.
42.
Bulpitt CJ, Beckett NS, Cooke J, Dumitrascu DL, Gil-Extremera B, Nachev C, Nunes M, Peters R, Staessen JA, Thijs L, on behalf of the Hypertension in the Very Elderly Trial (HYVET) Working Group: Orthostatic fall in blood pressure in the very elderly hypertensive: results from the Hypertension in the Very Elderly Trial (HYVET) – Pilot. Trial J Hypertens. 2003, 21: 2409-2417. 10.1097/00004872-200312000-00030.CrossRefPubMed
43.
Gueyffier F, Bulpitt C, Boissel JP, Schron E, Ekbom T, Fagard R, Casiglia E, Kerlikoske K, Coope J: Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet. 1999, 353: 793-6. 10.1016/S0140-6736(98)08127-6.CrossRefPubMed
44.
Lalande A, Roux C, Graulet AM, Schiavi P, De Vernejoul MC: The diuretic indapamide increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. J Bone Miner Res. 1998, 13: 1444-10.1359/jbmr.1998.13.9.1444.CrossRefPubMed
45.
Heidrich FE, Stergachis A, Gross KM: Diuretic drug use and the risk for hip fracture. Ann Intern Med. 1991, 115: 1-6.CrossRefPubMed
46.
Rejnmark L, Vestergaard P, Mosekilde L: Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens. 2006, 24: 581-589. 10.1097/01.hjh.0000203845.26690.cb.CrossRefPubMed
Metadata
Title
Fracture risk and the use of a diuretic (indapamide sr) ± perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET)
Authors
Christopher J Bulpitt
Ruth Peters
Jan A Staessen
Lutgarde Thijs
Marie-Christine De Vernejoul
Astrid E Fletcher
Nigel S Beckett
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Trials / Issue 1/2006
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-7-33

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