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U.S. Department of Health and Human Services

ALLHAT. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. Cardiovascular Outcomes in Hypertensives with CHD Randomized to Amlodipine versus Lisinopril in ALLHAT.

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U.S. Department of Health and Human Services

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  1. ALLHAT U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute Cardiovascular Outcomes in Hypertensives with CHD Randomized to Amlodipine versus Lisinopril in ALLHAT Frans Leenen MD, PhD, Chuke Nwachuku MA, MPH, Dr PH, William Cushman MD, Henry Black MD, Lara Simpson MS, Barry Davis MD, PhD. For the ALLHAT Collaborative Research Group Sponsored by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with the Department of Veterans Affairs www.allhat.org

  2. ALLHAT Background * Placebo-controlled RCT’s such as HOPE or EUROPA (but not PEACE) concluded that (hypertensive) patients with CHD show benefits from ACE-inhibitor therapy beyond that expected from BP lowering per se. on the other hand: * In the 90’s several mainly observational studies reported unfavorable cardiovascular outcomes on therapy with DHP-CCB’s in patients with CHD.

  3. ALLHAT Objective of Present Post-Hoc Analysis Comparison of cardiovascular and other outcomes among 18,102 patients with or without CHD at baseline randomized to the ACE-inhibitor lisinopril or the DHP-CCB amlodipine.

  4. ALLHAT Hypertension Trial 42,418 high-risk hypertensive patients 90% previously treated 10% untreated STEP 1 AGENTS Chlorthalidone 12.5-25 mg Amlodipine 2.5-10 mg Lisinopril 10-40 mg Doxazosin 1-8 mg N=9,061 N=9,054 N=9,048 N=15,255 STEP 2 AND 3 AGENTS (5 years) Hydralazine 10.9% Clonidine 10.6% Atenolol 28.0% Reserpine 4.3%

  5. ALLHAT CHD at Baseline “known prior MI, angina, primary cardiac arrest, coronary artery stenosis >50%, reversible perfusion defect, or major coronary revascularization procedure”

  6. ALLHAT Baseline Characteristics by CHD at Baseline

  7. ALLHAT 86 84 82 80 78 76 74 Baseline and Follow-up BPs by CHD at BL 148 146 144 Δ =1.8 142 Δ =1.5 140 mmHg BP Δ =1.2 138 Δ =0.8 Amlodipine - CHD at BL 136 Amlodipine - No CHD at BL 134 Lisinopril - CHD at BL 132 Lisinopril - No CHD at BL Δ =1.5 Δ =1.1 mmHg BP Δ =1.1 Δ =1.0 BL Y1 Y2 Y3 Y4 Mean # of Meds: Amlodipine CHD at BL 1.5 1.7 1.8 1.9 No CHD at BL 1.3 1.5 1.6 1.7 Lisinopril CHD at BL 1.5 1.7 1.8 1.9 No CHD at BL 1.5 1.6 1.8 2.0

  8. ALLHAT Events – L vs. ARelative Risk and 95% Confidence Intervals CHD 1.01 (0.91-1.11) Death 1.05 (0.97-1.13) Combined CHD 1.04 (0.97-1.12) Stroke 1.23 (1.08-1.41) p=0.047 Combined CVD 1.06 (1.00-1.12) ESRD 0.99 (0.77-1.26) Cancer 1.01 (0.91-1.12) GI Bleed 1.20 (1.06-1.37) HF 0.87 (0.78-0.96) p=0.045 Angina 1.09 (1.00-1.19) Revascularization 1.00 (0.91-1.11) PAD 1.19 (1.01-1.40) 0.50 1 2 Favors Lisinopril Favors Amlodipine

  9. ALLHAT Cumulative Event Rates for Primary Endpoint by CHD at Baseline and Treatment Group 0.20 0.20 CHD at BL No CHD at BL 0.15 0.15 Amlodipine Amlodipine 0.10 0.10 Cumulative CHD Rate Lisinopril Lisinopril 0.05 0.05 0.00 0.00 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years to Primary Endpoint Years to Primary Endpoint

  10. ALLHAT Secondary Endpoints:Lisinopril versus Amlodipine

  11. ALLHAT 0.10 CHD at BL Amlodipine 0.05 Lisinopril 0.00 0 1 2 3 4 5 6 7 Years to Stroke Cumulative Event Rates for Stroke by CHD at Baseline and Treatment Group 0.10 No CHD at BL Amlodipine 0.05 Cumulative Sstroke Rate Lisinopril 0.00 0 1 2 3 4 5 6 7 Years to Stroke

  12. ALLHAT Cumulative Event Rates for Heart Failure by CHD at Baseline and Treatment Group 0.20 0.20 CHD at BL No CHD at BL 0.15 0.15 Amlodipine Amlodipine 0.10 0.10 Cumulative HF Rate Lisinopril Lisinopril 0.05 0.05 0.00 0.00 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years to HF Years to HF

  13. ALLHAT Amlodipine Amlodipine Lisinopril Lisinopril Cumulative Event Rates for Angina by CHD at Baseline and Treatment Group 0.25 CHD at BL No CHD at BL 0.25 0.20 0.20 0.15 0.15 Cumulative ANG Rate 0.10 0.10 0.05 0.05 0.00 0.00 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years to Angina Years to Angina

  14. ALLHAT Cumulative Event Rates for PAD by CHD at Baseline and Treatment Group 0.10 0.10 CHD at BL No CHD at BL Amlodipine Amlodipine 0.05 0.05 Cumulative PAD Rate Lisinopril Lisinopril 0.00 0.00 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years to PAD Years to PAD

  15. ALLHAT Amlodipine Amlodipine Lisinopril Lisinopril Combined CVD 0.50 CHD at BL No CHD at BL 0.50 0.45 0.45 0.40 0.40 0.35 0.35 0.30 0.30 0.25 Cumulative CCVD Rate 0.25 0.20 0.20 0.15 0.15 0.10 0.10 0.05 0.05 0.00 0.00 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Years to CCVD Years to CCVD

  16. ALLHAT Summary

  17. ALLHAT Conclusion In hypertensive patients with CHD, lisinopril and amlodipine – based treatment provides equivalent BP control and equivalent rates for most outcomes. Patients with and without CHD have similar higher stroke rates and lower HF rates on lisinopril versus amlodipine. This post-hoc analysis provides no evidence for specific benefits by ACE-inhibitor based treatment in patients with CHD.

  18. ALLHAT Events for CHD by RaceRelative Risk and 95% Confidence Intervals Non-Blacks Blacks 0.95 (0.68-1.35) CHD 1.08 (0.90-1.30) 1.14 (0.87-1.49) Death 1.15 (0.97-1.36) 1.06 (0.82-1.37) Combined CHD 1.07 (0.95-1.22) 1.63 (1.01-2.64) Stroke 1.20 (0.89-1.62) 1.02 (0.84-1.24) Combined CVD 1.03 (0.93-1.15) 0.65 (0.33-1.29) ESRD 1.72 (0.68-4.38) 0.92 (0.61-1.40) Cancer 1.03 (0.82-1.31) 1.20 (0.78-1.86) GI Bleed 1.00 (0.77-1.30) 0.95 (0.66-1.35) HF 0.90 (0.73-1.11) 0.98 (0.73-1.33) Angina 0.99 (0.86-1.14) 1.17 (0.79-1.73) Revascularization 1.00 (0.84-1.19) 0.76 (0.43-1.35) PAD 0.98 (0.72-1.33) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Amlodipine Favors Lisinopril Favors Amlodipine

  19. ALLHAT Events for No CHD by RaceRelative Risk and 95% Confidence Intervals Non-Blacks Blacks 1.17 (0.95-1.43) CHD 0.91 (0.78-1.06) 1.08 (0.94-1.25) Death 0.96 (0.85-1.09) 1.14 (0.97-1.33) Combined CHD 0.97 (0.86-1.09) 1.48 (1.17-1.88) Stroke 1.00 (0.79-1.25) 1.16 (1.03-1.30) Combined CVD 1.02 (0.93-1.12) 1.03 (0.71-1.48) ESRD 0.97 (0.63-1.49) 1.10 (0.90-1.34) Cancer 0.95 (0.81-1.11) 1.30 (1.03-1.64) GI Bleed 1.27 (1.03-1.55) 0.87 (0.71-1.08) HF 0.83 (0.69-0.99) 1.24 (1.01-1.52) Angina 1.12 (0.96-1.31) 1.08 (0.81-1.45) Revascularization 0.95 (0.82-1.12) 1.44 (1.03-2.02) PAD 1.35 (1.04-1.77) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Amlodipine Favors Lisinopril Favors Amlodipine

  20. ALLHAT CHD at Baseline No CHD at Baseline CHD 1.08 (0.90-1.30) 0.91 (0.78-1.06) Death 1.15 (0.97-1.36) 0.96 (0.85-1.09) Combined CHD 1.07 (0.95-1.22) 0.97 (0.86-1.09) Stroke 1.20 (0.89-1.62) 1.00 (0.79-1.25) Combined CVD 1.03 (0.93-1.15) 1.02 (0.93-1.12) 0.65 (0.33-1.29) ESRD 0.97 (0.63-1.49) Cancer 1.03 (0.82-1.31) 0.95 (0.81-1.11) GI Bleed 1.00 (0.77-1.30) 1.27 (1.03-1.55) HF 0.90 (0.73-1.11) 0.83 (0.69-0.99) Angina 0.99 (0.86-1.14) 1.12 (0.96-1.31) Revascularization 1.00 (0.84-1.19) 0.95 (0.82-1.12) PAD 0.98 (0.72-1.33) 1.35 (1.04-1.77) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Amlodipine Favors Lisinopril Favors Amlodipine Events for Non-Blacks by CHD StatusRelative Risk and 95% Confidence Intervals

  21. ALLHAT CHD at Baseline No CHD at Baseline CHD 0.95 (0.68-1.35) 1.17 (0.95-1.43) Death 1.14 (0.87-1.49) 1.08 (0.94-1.25) Combined CHD 1.06 (0.82-1.37) 1.14 (0.97-1.33) Stroke 1.63 (1.01-2.64) 1.48 (1.17-1.88) Combined CVD 1.02 (0.84-1.24) 1.16 (1.03-1.30) ESRD 1.03 (0.71-1.48) 1.72 (0.68-4.38) Cancer 0.92 (0.61-1.40) 1.10 (0.90-1.34) GI Bleed 1.20 (0.78-1.86) 1.30 (1.03-1.64) HF 0.95 (0.66-1.35) 0.87 (0.71-1.08) Angina 0.98 (0.73-1.33) 1.24 (1.01-1.52) Revascularization 1.17 (0.79-1.73) 1.08 (0.81-1.45) PAD 0.76 (0.43-1.35) 1.44 (1.03-2.02) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Amlodipine Favors Lisinopril Favors Amlodipine Events for Blacks by CHD StatusRelative Risk and 95% Confidence Intervals

  22. ALLHAT Outcomes L vs. A:RR and 95% Confidence Intervals CHD at Baseline No CHD at Baseline CHD 1.05 (0.89-1.24) 0.99 (0.88-1.13) Death 1.15 (0.99-1.32) 1.01 (0.92-1.11) Combined CHD 1.07 (0.96-1.20) 1.02 (0.93-1.12) Stroke 1.31 (1.01-1.69) 1.20 (1.02-1.41) Combined CVD 1.03 (0.94-1.13) 1.07 (0.99-1.15) ESRD 0.92 (0.54-1.56) 1.00 (0.76-1.32) Cancer 1.01 (0.82-1.24) 1.01 (0.89-1.14) GI Bleed 1.05 (0.84-1.32) 1.28 (1.10-1.50) HF 0.91 (0.76-1.09) 0.85 (0.74-0.97) Angina 0.99 (0.87-1.12) 1.17 (1.03-1.32) Revascularization 1.03 (0.88-1.20) 0.98 (0.86-1.13) PAD 0.93 (0.71-1.21) 1.39 (1.12-1.71) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Amlodipine Favors Lisinopril Favors Amlodipine

  23. ALLHAT Outcomes A vs. C:RR and 95% Confidence Intervals CHD at Baseline No CHD at Baseline CHD 0.95 (0.82-1.10) 1.01 (0.90-1.13) Death 0.89 (0.79-1.01) 0.99 (0.91-1.08) Combined CHD 1.02 (0.92-1.13) 1.02 (0.93-1.11) Stroke 0.90 (0.71-1.13) 0.96 (0.82-1.11) Combined CVD 1.07 (0.98-1.16) 1.05 (0.98-1.12) ESRD 0.88 (0.56-1.38) 1.23 (0.95-1.60) Cancer 0.92 (0.77-1.10) 1.06 (0.95-1.18) GI Bleed 1.00 (0.82-1.23) 0.88 (0.76-1.02) HF 1.29 (1.09-1.52) 1.48 (1.30-1.68) Angina 1.10 (0.98-1.24) 0.99 (0.88-1.11) Revascularization 1.16 (1.00-1.33) 1.08 (0.96-1.23) PAD 1.04 (0.82-1.31) 0.79 (0.66-0.96) 0.50 1 2 0.50 1 2 Favors Amlodipine Favors Chlorthalidone Favors Amlodipine Favors Chlorthalidone

  24. ALLHAT Outcomes A vs. C in Blacks:RR and 95% Confidence Intervals CHD at Baseline in Blacks No CHD at Baseline in Blacks 1.19 (0.87-1.61) 0.95 (0.79-1.15) CHD 0.96 (0.76-1.23) 0.99 (0.87-1.13) Death 1.19 (0.94-1.50) 1.00 (0.87-1.16) Combined CHD 0.89 (0.56-1.42) 0.96 (0.76-1.21) Stroke 1.16 (0.97-1.38) 1.05 (0.94-1.16) Combined CVD 0.70 (0.29-1.68) 1.27 (0.90-1.80) ESRD 1.07 (0.75-1.55) 0.95 (0.79-1.14) Cancer 0.94 (0.63-1.39) 1.01 (0.81-1.26) GI Bleed 1.47 (1.06-2.04) HF 1.53 (1.26-1.88) 1.08 (0.83-1.41) Angina 1.10 (0.91-1.35) 1.37 (0.94-1.99) Revascularization 0.97 (0.75-1.27) 1.18 (0.73-1.91) PAD 0.77 (0.56-1.05) 0.50 1 2 0.50 1 2 Favors Amlodipine Favors Chlorthalidone Favors Amlodipine Favors Chlorthalidone

  25. ALLHAT Outcomes A vs. C in Non-Blacks:RR and 95% Confidence Intervals CHD at Baseline in Non-Blacks No CHD at Baseline in Non-Blacks 1.04 (0.91-1.10) CHD 0.89 (0.76-1.05) 0.99 (0.89-1.11) Death 0.87 (0.75-1.01) 1.02 (0.92-1.17) Combined CHD 0.98 (0.87-1.10) 0.95 (0.78-1.16) Stroke 0.90(0.69-1.18) 1.05 (0.97-1.14) Combined CVD 1.04 (0.95-1.14) 1.18 (0.79-1.74) ESRD 1.96 (0.56-1.62) 1.13 (0.98-1.30) Cancer 0.87 (0.71-1.08) 0.80 (0.67-0.97) GI Bleed 1.03 (0.81-1.30) 1.44 (1.23-1.70) HF 1.24 (1.03-1.49) 0.94 (0.82-1.08) Angina 1.11 (0.97-1.26) 1.12 (0.97-1.29) Revascularization 1.12 (0.96-1.30) 0.81 (0.64-1.04) PAD 1.00 (0.76-1.31) 0.50 1 2 0.50 1 2 Favors Amlodipine Favors Chlorthalidone Favors Amlodipine Favors Chlorthalidone

  26. ALLHAT Outcomes L vs. C:RR and 95% Confidence Intervals CHD at Baseline No CHD at Baseline CHD 1.00 (0.87-1.15) 1.00 (0.90-1.12) Death 1.02 (0.91-1.15) 1.01 (0.93-1.09) Combined CHD 1.09 (0.99-1.21) 1.04 (0.96-1.13) Stroke 1.17 (0.95-1.45) 1.15 (1.00-1.32) Combined CVD 1.10 (1.01-1.19) 1.12 (1.05-1.20) ESRD 0.80 (0.51-1.28) 1.23 (0.95-1.60) Cancer 0.93 (0.77-1.11) 1.06 (0.95-1.19) GI Bleed 1.06 (0.87-1.29) 1.13 (1.00-1.29) HF 1.18 (1.00-1.39) 1.25 (1.09-1.43) Angina 1.09 (0.97-1.22) 1.16 (1.04-1.29) Revascularization 1.18 (1.03-1.36) 1.06 (0.94-1.21) PAD 0.96 (0.76-1.22) 1.10 (0.92-1.31) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Chlorthalidone Favors Lisinopril Favors Chlorthalidone

  27. ALLHAT Outcomes L vs. C in Blacks:RR and 95% Confidence Intervals CHD at Baseline in Blacks No CHD at Baseline in Blacks 1.14 (0.83-1.55) CHD 1.11 (0.93-1.33) 1.10 (0.88-1.39) Death 1.07 (0.95-1.22) 1.26 (1.01-1.59) Combined CHD 1.14 (0.99-1.32) 1.45 (0.98-2.16) Stroke 1.43 (1.16-1.76) 1.18 (0.99-1.40) Combined CVD 1.22 (1.10-1.35) 1.21 (0.58-2.52) ESRD 1.30 (0.92-1.83) 1.00 (0.69-1.45) Cancer 1.04 (0.88-1.24) 1.13 (0.78-1.64 GI Bleed 1.32 (1.07-1.62) 1.39 (0.99-1.94) HF 1.34 (1.09-1.65) 1.06 (0.81-1.38) Angina 1.37 (1.14-1.65) 1.59(1.11-2.28) Revascularization 1.05 (0.81-1.36) 0.90 (0.54-1.53) PAD 1.11 (0.84-1.47) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Chlorthalidone Favors Lisinopril Favors Chlorthalidone

  28. ALLHAT Outcomes L vs. C in Non-Blacks:RR and 95% Confidence Intervals CHD at Baseline in Non-Blacks No CHD at Baseline in Non-Blacks CHD 0.97(0.83-1.13) 0.94 (0.82-1.09) Death 1.00 (0.86-1.15) 0.96 (0.86-1.07) Combined CHD 1.05 (0.94-1.17) 0.99 (0.89-1.10) Stroke 1.08 (0.83-1.39) 0.95 (0.77-1.16) Combined CVD 1.08 (0.98-1.18) 1.07 (0.99-1.16) 0.63 (0.34-1.16) 1.15 (0.77-1.71) ESRD Cancer 0.91 (0.74-1.11) 1.08 (0.93-1.24) GI Bleed 1.03 (0.82-1.30) 1.02 (0.85-1.21) HF 1.12 (0.92-1.35) 1.19 (1.00-1.42) Angina 1.10 (0.96-1.24) 1.06 (0.92-1.21) Revascularization 1.12 (0.96-1.30) 1.07 (0.93-1.24) PAD 0.98 (0.75-1.28) 1.10 (0.88-1.37) 0.50 1 2 0.50 1 2 Favors Lisinopril Favors Chlorthalidone Favors Lisinopril Favors Chlorthalidone

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