Studie Hyvet a HYVET-COG
Léčba velmi starých hypertoniků

Czech version

Authors: J. Widimský
Published in: Kardiol Rev Int Med 2008, 10(4): 141-146

Overview

The effect of hypertensi on tre atment on cognitive faculti es – HYVET- COG study. Until recently, it was not known whether very old pe ople co uld also benefit from the tre atment of hypertensi on. The HYVET study presents the first prospective, do uble- blind study evalu ating the effect of antihypertensive tre atment in the above age gro up (80 ye ars and above). A total of 3,845 pati ents with me an age 83.6 ye ars were randomised to an active therapy gro up and a placebo gro up. The average se ated blo od pressure pri or to the start of therapy was 173.0/ 90.8 mmHg. Indapamide 1.5 mg was used for active therapy. A dose of 2 mg or 4 mg of perindopril co uld be added to the active tre atment if BP target values < 150/ < 80 mmHg were not achi eved. After two ye ars of durati on of the study, the average se ated BP in the actively tre ated gro up was by 15.0/ 6.1 mmHg lower as compared with the placebo gro up. The target BP values < 150/ < 80 mmHg were achi eved in almost 50 % of pati ents. The HYVET study was prematurely discontinued on ethical gro unds by the data monitoring committee after a 1.8 ye ar tre atment medi an as a result of a significant difference in the total mortality and fatal cerebrovascular events rates in favo ur of the actively tre ated gro up. Overall mortality was significantly reduced by 21 % (p = 0.02), fatal cerebrovascular events by 39 % (p = 0.045), and the incidence of he art failure by 64 % (p < 0.001). The tre atment was very well tolerated and the incidence of adverse effects was lower than in the placebo gro up. The HYVET study provides important evidence of the fact that the tre atment of hypertensi on in very old persons based on indapamide (with sustained rele ase) combined with perindopril in more than 70 % of pati ents brings a highly positive result in very old hypertonic pati ents and reduces the risk of de ath for all ca uses, as well as fatal cerebrovascular events and the incidence of he art failure. The HYVET- COG study which forms part of the HYVET study was focused on the issue of the relati on between the tre atment of hypertensi on and cognitive decline and the incidence of dementi a. The study has shown that tre atment of hypertensi on in very old pe ople results in a trend towards a less cognitive decline and towards lower incidence of dementi a. The above decre ase has not assumed statistical significance mainly beca use of the fact that the study had to be prematurely interrupted for a significant difference in overall mortality and in the incidence of fatal cerebrovascular events. However, meta‑analysis of the fo ur studi es focussing the issue of preventi on of dementi a within primary or secondary preventi on showed the capacity of hypertensi on tre atment to significantly decre ase the incidence of dementi a.

Key words:
hypertension in very old people – HYVET study – hypertension treatment – prevention of dementia – HYVET-COG

Sources

1. Gueyffi er F, Bulpitt C, Bo issel JP et al. Antihypertensive drugs in very old pe ople: a subgro up meta‑analysis of randomised controlled tri als. INDANA Gro up. Lancet 1999; 353: 793- 796.

2. Bulpitt CJ, Beckett NS, Co oke J et al on behalf of Hypertensi on in the Very Elderly Tri al (HYVET) Working Gro up. Results from the pilot study for Hypertensi on in the Very Elderly Tri al. J Hypertens 2003; 21: 2409– 2417.

3. Beckett NS, Peters R, Fletcher AE et al for the HYVET Study Gro up. Tre atment of hypertensi on in pati ents 80 ye ars of age or older. N Engl J Med 2008; 358: 1887– 1898.

4. Staessen JA, Fagard R, Thijs L et al for the Systolic Hypertensi on- Europe (Syst- Eur) Tri al Investigators. Morbidity and mortality in the placebo- controlled Europe an Tri al on Isolated Systolic Hypertensi on in the Elderly. Lancet 1997; 360: 757– 764.

5. Dahlöf B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Tri al in Old Pati ents with Hypertensi on (STOP Hypertensi on). Lancet 1991; 338: 1281– 1285.

6. Ambrosi oni E, Safar M, Dega ute JP et al. Low‑dose antihypertensive therapy with 1,5 mg sustained- rele ase indapamide: results of the randomised do uble- blind controlled studi es. Europe an Study Gro up. J Hypertens 1998; 16: 1677– 1688.

7. Eli as MF, Wolf PA, D’Agostino RB et al. Untre ated blo od pressure level is inversely related to cognitive functi oning: the Framingham study. Am J Epidemi ol 1993; 138: 353– 364.

8. Sko og I, Lernfelt B, Landahl S et al. 15- ye ar longitudinal study of blo od pressure and dementi a. Lancet 1996; 347: 1131– 1135.

9. Birkenhäger WH, Forette F, Se ux ML et al. Blo od pressure, cognitive functi ons, and preventi on of dementi as in older pati ents with hypertensi on. Arch Intern Med 2001; 161: 152– 156.

10. La uner LJ, Masaki K, Petrovitch H et al. The associ ati on between midlife blo od pressure levels and late‑life cognitive functi on. The Honolulu- Asi a Aging Study. JAMA 1995; 274: 1845– 1851.

11. Kari o K, Pickering TG, Umeda Y et al. Morning surge in blo od pressure as a predictor of silent and clinical cerebrovascular dise ase in elderly hypertensives: a prospective study. Circulati on 2003; 107: 1401– 1405.

12. Forette F, Se ux ML, Staessen JA et al. The preventi on of dementi a with antihypertensive tre atment: new evidence from the Systolic Hypertensi on in Europe (Syst- Eur) study. Arch Intern Med 2002; 162: 2046– 2052.

13. Forette F, Se ux ML, Thijs L et al. Antihypertensive tre atment and preventi on of dementi a in older pati ents with isolated systolic hypertensi on: The Syst- Eur results. J Hypertens 1998; 16: 22.

14. Applegate WB, Pressel S, Wittes J et al. Impact of the tre atment of isolated systolic hypertensi on on behavi oral vari ables: results from the Systolic Hypertensi on in the Elderly Program. Arch Intern Med 1994; 154: 2154– 2160.

15. Peters R, Beckett N, Forette F et al for the HYVET investigators. Incident dementi a and blo od pressure lowering in the Hypertensi on in the Very Elderly Tri al cognitive functi on assessment (HYVET- COG): a do uble- blind, placebo controlled tri al. Lancet Ne urol 2008; 7: 683– 689. http:/ / www.thelancet.com/ ne urology.

16. Folstein MF, Folstein SE, McHugh PR. „Mini‑Mental State“. A practical method for grading the cognitive state of pati ents for the clinici an. J Psychi at Res 1975; 12: 189– 198.

17. Widimský J et al. Hypertenze. 3. vyd. Triton Praha 2008.

18. PROGRESS Collaborative Gro up. Randomised trail of perindopril‑based blo od- pressure‑lowering regimen among 6,105 individu als with previ o us stroke or transi ent ischaemic attack. Lancet 2001; 358: 1033– 1041.

19. Tzo uri o C, Anderson C, Chapman N et al for The PROGRESS Collaborative Gro up. Effects of blo od pressure lowering with perindopril and indapamide therapy on dementi a and cognitive decline in pati ents with cerebrovascular dise ase. Arch Intern Med 2003; 163: 1069– 1075.