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TRANSCEND

TRANSCEND: T elmisartan R andomized A ssesme N t S tudy in a CE i N tolerant S ubjects with C ardiovascular D isease ONTARGET / TRANSCEND Investigators Koon K. Teo , MB, PhD, FRCPC. Question :

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TRANSCEND

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  1. TRANSCEND:TelmisartanRandomizedAssesmeNtStudy in aCEiNtolerantSubjects with Cardiovascular DiseaseONTARGET / TRANSCEND InvestigatorsKoon K. Teo, MB, PhD, FRCPC

  2. Question: Is telmisartan superior to placebo in patients at high risk of CV events who are intolerant of ACE-I? Outcome: Primary: CV death, MI, stroke, CHF hosp Key secondary: CV death, MI, stroke (HOPE trial outcome) Design: Single blind run-in (n=6,666) Randomized, double blind, placebo controlled study conducted in 630 centers in 40 countries (n=5,926) 56 months follow-up with 99.7% outcome ascertainment TRANSCEND

  3. Trial Profile 6666 entered Run-in 5926 patients randomized 2954 assigned telmisartan (80mg) 2972 assigned placebo 10 lost to follow-up 8 lost to follow-up 2944 completed study 2964 completed study

  4. History at Randomization (%)

  5. Change in Sitting Systolic BP (mm Hg)From Pre-Run-in Over Time

  6. Concomitant Medications by Visit (%) *P<0.0001, compared to Telmisartan

  7. Time to Permanent Discontinuation of Study Medication 0.4 # at Risk Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 T 2954 2784 2663 2547 2271 1086 Pl 2972 2814 2629 2509 2242 1063 0.3 Telmisartan Cumulative Hazard Rates Placebo 0.2 0.1 0.0 0 1 2 3 4 5 Years of Follow-up

  8. Reasons for Permanently Stopping Study Medications

  9. Primary Outcome & HOPE: Primary Outcome

  10. Time to Primary Outcome 0.20 Telmisartan 0.15 Placebo Cumulative Incidence Rates 0.10 0.05 HR: 0.92 (0.81-1.05) P-value = 0.2158 0.0 0 1 2 3 4 5 Years of Follow-up No. at Risk T 2954 2807 2699 2577 2278 1091 Pl 2972 2839 2713 2575 2253 1069

  11. Time to Secondary Outcome 0.20 Telmisartan Placebo 0.15 Cumulative Incidence Rates 0.10 HR: 0.87 (0.76 – 1.00) P-value = 0.0475 0.05 0.0 0 1 2 3 4 5 Years of Follow-up No. at Risk T 2954 2839 2745 2634 2344 1127 Pl 2972 2866 2745 2626 2306 1103

  12. Primary and Key - Secondary Outcomes

  13. ADVANCE: Analyses of Macro + Microvascular Outcome *P for interaction

  14. ADVANCE:Macro + Microvascular including Microalb *P for interaction

  15. Subgroup Analysis of Primary Outcome Incidence (%) p for Placebo Group interaction No. Patients Primary Composite 5926 17.0 Hx of CVD 5418 17.2 0.6102 505 14.1 No Hx of CVD SBP <= 133 1955 16.2 133 < SBP <= 149 1996 15.8 0.7956 SBP > 149 1969 18.8 Diabetes 2118 19.9 0.3109 No Diabetes 3805 15.3 HOPE Score <= 3.624 1978 9.3 3.624<= HOPE Score <= 4.034 1934 16.1 0.4615 HOPE Score > 4.034 2014 25.4 Age < 65 2375 13.5 65 <= Age < 75 2576 16.9 0.8945 Age >= 75 975 25.7 Male 3379 18.9 0.0842 Female 2547 14.4 Statin 3272 16.2 0.2867 No Statin 2654 17.9 Telmisartan better Placebo better 0.4 0.7 1.0 1.3 1.6 HR(95% CI)

  16. Telmisartan Meta-analysis (CV Death, MI, Stroke, CHF Hosp) No. events/No. randomized p-value Telmisartan Placebo 0.067 PROFESS 1367/10146 (13.5%) 1463/10186 (14.4%) 0.205 TRANSCEND 466/2954 (15.7%) 505/2972 (17.0%) 0.026 OVERALL 1833/13100 (14.0%) 1968/13158 (14.9%) 0.075 OVERALL <= 6M 546/13100 (4.2%) 492/13158 (3.7%) <0.001 OVERALL > 6M 1287/12484 (10.3%) 1476/12575 (11.7%) Telmisartan better Placebo better 0.7 0.8 0.9 1.0 1.1 1.2 OR (95% CI)

  17. Telmisartan Meta-analysis (CV Death, MI, Stroke) No. events/No. randomized P-value Telmisartan Placebo 0.086 PROFESS 1289/10146 (12.7%) 1377/10186 (13.5%) 0.045 TRANSCEND 385/2954 (13.0%) 441/2972 (14.8%) 0.013 OVERALL 1674/13100 (12.8%) 1818/13158 (13.8%) 0.074 OVERALL <= 6M 502/13100 (3.8%) 450/13158 (3.4%) <0.001 OVERALL > 6M 1172/12526 (9.3%) 1368/12616 (10.8%) Telmisartan better Placebo better 0.7 0.8 0.9 1.0 1.1 1.2 OR (95% CI)

  18. Conclusions: Telmisartan vs. Placebo • Telmisartan reduces the primary outcome by 8% (P=0.22), but reduces significantly the main secondary outcome of CV death, MI or stroke by 13% (P=0.048). • There is no impact on heart failure events with telmisartan. • Telmisartan is well tolerated and there is no excess of adverse events

  19. TRANSCEND and PROFESS Meta-Analysis • Clear reduction in the relative risk of the composite of CV death, MI or stroke by 9% (p=0.013), with little effect in the first 6 months after randomization, but a 15% RRR after 6 months (significant heterogeneity over the two time periods). • Neutral effect of telmisartan on heart failure events, which is surprising (OR of 1.00, 95% CI of 0.85 to 1.17), but this is consistent with the results of HF in ONTARGET (more events with telmisartan compared to ramipril). • Lower rates of MI and stroke.

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