The role of cardiac devise therapy in heart2021 ihab
Hyvet Slide Set
1. First clear evidence for the treatment of hypertensive patients aged 80 or over with Natrilix SR
2. Agenda Importance of hypertension in the very elderly HYVET design Baseline characteristics of HYVET population HYVET results Clinical implications
3. World Population Ageing 1950-2050, Population Div., DESA, United Nations Global increase in population aged 80 and over 13.8 69.2 153.4 379.0 31.4
4.
5.
6. The heart failure epidemic Thom T et al. Circulation. 2006;113:e85–e151. Hospital discharges for heart failure Discharges in thousands 600 500 400 300 200 100 0 1979 1983 1987 1991 1995 1999 2003 Year Males Females + 174%
7.
8.
9.
10. 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Treatment better Stroke events (-36%, P =0.01) Total mortality (+14%, P =0.05) Major cardiovascular events (-23 %, P =0.01) Heart failure (-42 %, P =0.01) Double-blind trials Gueyffier F, et al. Lancet. 1999:353:793-796. Control better Treatment reduces CV events but not overall mortality INDANA meta-analysis 0
11.
12. What do guidelines say? “ In subjects aged 80 years or over, evidence for antihypertensive treatment is as yet inconclusive ” ESH/ESC 2007 “ offer patients over 80 years of age the same treatment as other patients over 55, taking account of any comorbidity and their existing burden of drug use, but patients over 80 years of age are poorly represented in clinical trials and the effectiveness of treatment in this group is less certain” NICE 2007 “ For those aged over 80 at the time of diagnosis of hypertension, no clear guidance can be given” BHS 2004 No mention of over-80s, treated as other patients JNC7 2003 Statement Guidelines
13. HYVET results eagerly awaited The results of the HYVET trial “should eventually provide reliable evidence about the effect of BP–lowering therapy in this very high-risk population” WHO/ISH guidelines 1999
14. This dilemma provided the rationale for the HY pertension in the V ery E lderly T rial To treat or not to treat? That is the question Increase in mortality Reduction in strokes
15. HYVET, an international trial The trial: International, multicenter, randomized, double-blind, placebo-controlled Inclusion criteria: Exclusion criteria: Aged 80 or more, Standing SBP <140 mm Hg Systolic BP 160-199 mm Hg Stroke in last 6 months + diastolic BP <110 mm Hg, Dementia Informed consent Need for daily nursing care Primary end point: All strokes (fatal and nonfatal)
19. Patient characteristics ‡ Fall in SBP ≥ 20 mm Hg and/or fall in DBP ≥ 10 mm Hg Beckett N, et al. NEJM 2008;358:1887-1898. Placebo (n= 1912) Natrilix SR +/- Coversyl (n= 1933) Age (years) 83.5 83.6 Female 60.3% 60.7% Blood pressure : Sitting SBP (mm Hg) 173.0 173.0 Sitting DBP (mm Hg) 90.8 90.8 Orthostatic hypotension ‡ 8.8% 7.9% Isolated systolic hypertension 32.6% 32.3%
20. Patient characteristics ( cardiovascular history ) Beckett N, et al. NEJM 2008;358:1887-1898. 11.5 12.0 Cardiovascular disease 2.9 2.9 Heart failure 3.1 3.2 Myocardial infarction 6.7 6.9 Stroke 64.2 65.1 Antihypertensive treatment 89.9 89.9 Known hypertension Natrilix SR +/- Coversyl (%) Placebo (%)
21. Patient characteristics (c ardiovascular risk factors ) Beckett N, et al. NEJM 2008;358:1887-1898. Placebo Natrilix SR +/- Coversyl Current smoker 6.6% 6.4% Diabetes (known DM/DM treatment/glucose>11.1 mmo/L) 6.9% 6.8% Total cholesterol (mmol/L) 5.3 5.3 HDL cholesterol (mmol/L) 1.35 1.35 Serum creatinine (μmol/L) 89.2 88.6 Uric acid (µmol/L) 279 280 Body mass index (kg/m 2 ) 24.7 24.7
22.
23. Total mortality (21% reduction) Placebo P =0.02 Natrilix SR Based Regimen Number of events per 100 patients Follow-up (years) Beckett N, et al. NEJM 2008;358:1887-1898. This result is at odds with findings from previous trials
24. All stroke (30% reduction) Placebo P =0.06 Natrilix SR Based Regimen Number of events per 100 patients Follow-up (years) Beckett N, et al. NEJM 2008;358:1887-1898.
25. Fatal stroke (39% reduction) P =0.046 Placebo Natrilix SR Based Regimen Number of events per 100 patients Follow-up (years) Beckett N, et al. NEJM 2008;358:1887-1898.
26. Heart failure (64% reduction) Placebo P <0.001 Natrilix SR Based Regimen Number of events per 100 patients Follow-up (years) Beckett N, et al. NEJM 2008;358:1887-1898.
27. ITT – Summary Beckett N, et al. NEJM 2008;358:1887-1898. 1 2 0.5 0.2 0.1 95% CI RRR (0.53, 0.82) -34% (0.22, 0.58) -64% (0.42, 1.19) -29% (0.60, 1.01) -23% (0.62, 1.06) -19% (0.65, 0.95) -21% (0.38, 0.99) -39% (0.49, 1.01) -30% CV events Heart failure Cardiac death CV death NonCV/Unknown death All-cause mortality Stroke death All strokes
28. Per protocol Results are linked to Natrilix SR’s protection of the heart and brain Beckett N, et al. NEJM 2008;358:1887-1898. 0.17 - 0.48 0.55 - 0.97 0.33 - 0.93 0.59 - 0.88 0.46 - 0.95 95% CI 0.03 -27% Cardiovascular mortality -72% -45% -28% -34% RRR <0.001 0.02 0.001 0.03 P All strokes Total mortality Fatal strokes Heart failure
29.
30.
31.
32.
33.
34.
35.
Editor's Notes
HYVET is the first and the largest hypertension trial carried out in patients aged 80 or over. This study specifically addresses the question whether active antihypertensive therapy with a Natrilix SR-based regimen is associated with a major and significant reduction in cardiovascular morbidity and mortality in this age group.
