Presentation is loading. Please wait.

Presentation is loading. Please wait.

Is there evidence to justify different claims for different drug classes? Presentation to: Cardiovascular & Renal Drugs Advisory Committee Food & Drug.

Published byAlexandra Casey Modified over 9 years ago

Similar presentations

Presentation on theme: "Is there evidence to justify different claims for different drug classes? Presentation to: Cardiovascular & Renal Drugs Advisory Committee Food & Drug."— Presentation transcript:

1 Is there evidence to justify different claims for different drug classes? Presentation to: Cardiovascular & Renal Drugs Advisory Committee Food & Drug Administration Rockville MD, June 15, 2005 Stephen W. MacMahon, B.Sc., Ph.D., M.P.H., F.A.C.C.

2 Blood Pressure Lowering Treatment Trialists’ Collaboration 1995-2005 Secretariat: The George Institute, University of Sydney & Royal Prince Alfred Hospital Principal sponsor: National Health & Medical Research Council of Australia

3  1 st cycle published Lancet 2000; 355:1955-64  2 nd cycle published Lancet 2003; 362:1527-35  29 randomised trials  162,341 patients  More than 700,000 patient years Analysis cycles

4  Active vs. control  ACE-I vs placebo  CA vs placebo  More intensive vs less intensive  ARB vs. other regimen  Active vs. active  ACE-I vs diuretic/beta-blocker*  CA vs diuretic/beta-blocker*  ACE-I vs CA Treatment comparisons

5  Active vs. control  ACE-I vs placebo  CA vs placebo  More intensive vs less intensive  ARB vs. other regimen  Active vs. active  ACE-I vs diuretic/beta-blocker*  CA vs diuretic/beta-blocker*  ACE-I vs CA Treatment comparisons

6  Most trials compared treatment regimens rather single drugs  Regimens were usually based on a specific agent with the addition of others as required for BP control  In active vs. active comparisons, the control condition was pre-specified as diuretic- or beta-blocker-based therapy (mostly diuretic) Treatment comparisons

7 ACE inhibitor vs. diuretic/beta-blocker Total participants Major events AASK877NA ALLHAT243091195 ANBP26083509 CAPPP10985698 STOP-24418897 UKPDS-HDS758141 Total474306031

8 Calcium antagonist vs. diuretic/beta-blocker Total participants Major events AASK658NA ALLHAT243033704 CONVINCE16476729 ELSA233460 INSIGHT6321407 NICS-EH23923 NORDIL10881803 SHELL1882172 STOP-24409910 VHAS141429 Total684496837

9 ACE inhibitor vs. calcium antagonist Total participants Major events AASK653NA ABCD (H)47075 ABCD (N)48076 ALLHAT181022838 JMIC-B165088 STOP-24401887 Total257563964

10 RR (95% CI) Favours first listed Favours second listed 0.51.02.0 Relative Risk BP difference (mm Hg) 1.09 (1.00,1.18) ACE vs. D/BB 0.93 (0.86,1.00) CA vs. D/BB 1.12 (1.01,1.25) ACE vs. CA 2/0 1/0 1/1 Active vs. active Stroke

11 RR (95% CI) Favours first listed Favours second listed BP difference (mm Hg) 0.51.02.0 Relative Risk 0.96 (0.88,1.04) 1.01 (0.94,1.08) 0.98 (0.91,1.05) ACE vs. CA CA vs. D/BB ACE vs. D/BB 2/0 1/0 1/1 Active vs. active Coronary heart disease

12 RR (95% CI) Favours first listed Favours second listed BP difference (mm Hg) 0.51.02.0 Relative Risk 1.07 (0.96,1.19) ACE vs. CA CA vs. D/BB ACE vs. D/BB 1.33 (1.21,1.47) 0.82 (0.73,0.92) 2/0 1/0 1/1 Active vs. active Heart failure

13 RR (95% CI) Favours first listed Favours second listed BP difference (mm Hg) 0.51.02.0 Relative Risk ACE vs. CA CA vs. D/BB ACE vs. D/BB 0.97 (0.92,1.03) 1.04 (1.00,1.09) 1.02 (0.98,1.07) 2/0 1/0 1/1 Active vs. active Composite major CVD events

14 Active vs. active Composite major CVD events (diabetes subgroups) Risk ratio 0.250.512 0.90 (0.74,1.11) 1.04 (0.98,1.04) 1.02 (0.95,1.10) 1.04 (0.99,1.10) 0.92 (0.79,1.07) 0.99 (0.92,1.07) p homog =0.20 p homog =0.83 p homog =0.37 2.2/0.3 1.4/0.2 ACE-I vs. D/BB Diabetes No diabetes CA vs. D/BB Diabetes No diabetes ACE-I vs. CA Diabetes No diabetes  BP ( mmHg ) RR(95%CI) Favours first listed Favours second listed 0.7/-0.8 1.1/-0.4 1.6/1.2 1.3/0.9 Overall Arch Int Med 2005: in press

15 0.250.512 Major CVD Diabetes No diabetes 0.90 (0.82,0.99) 0.90 (0.81,1.00) -2.1/-0.9 -1.4/-0.6 p homog=0.94 CV deaths Diabetes No diabetes 0.99 (0.77,1.28) 0.95 (0.81,1.12) -2.1/-0.9 -1.4/-0.6 p homog=0.79 Total mortality Diabetes No diabetes -2.1/-0.9 -1.4/-0.6 0.91 (0.75,1.10) 0.97 (0.86,1.09) p homog=0.55 ARB-based regimens vs. others Composite outcomes (diabetes subgroups)  BP (mmHg) RR(95%CI) Favours ARB Favours Other Overall Arch Int Med 2005: in press

16  Calcium antagonist and D/BB-based regimens may be more effective than ACE inhibitors for stroke prevention  ACE inhibitors and D/BB regimens are more effective than CA-based regimens for heart failure prevention  No differences between regimens in effects on coronary heart disease Conclusions

17  For total cardiovascular events, there were very similar effects of:  ACE inhibitor-  calcium antagonist-  D/BB-based regimens  ARB-based regimens also reduced total CV events  Effects of all drug classes similar in diabetic and non-diabetic patients Conclusions

18 Independent drug effects?  Primary focus of debate for past decade, with no consensus  Main hypothesis concerns potential advantages of agents that inhibit the renin angiotensin system  Do ACE inhibitors and angiotensin receptor blockers confer benefits “beyond blood pressure reduction”

19 Effects of RAS inhibitors  In trials of active vs. active regimens  No clear advantage of ACE inhibitor-based regimens compared with D/BB-based regimens  But moderate differences between regimens in BP lowering effects  In trials of ARB-based regimens  Uncertainty as to whether benefits are greater than those expected given the reduction in BP

20 Effects of RAS inhibitors  New analysis  Effects of ACE-I and ARB-based regimen vs. any other comparator  Stratified by BP differences between randomized groups  Cause-specific outcomes: stroke, coronary heart disease, heart failure* *trials with calcium antagonist control treatment excluded from heart failure analyses, given clear evidence of differential effect of these agents

21 "This slide contains unpublished data. If you have any questions regarding these data, please contact Stephen W. MacMahon, B.Sc., Ph.D., M.P.H., F.A.C.C., Principal Director, Professor of Cardiovascular Medicine and Epidemiology, The George Institute for International Health, The University of Sydney."

22

23

24

25 Conclusions  For all regimens, size of BP reduction directly related to size of risk reduction  For coronary heart disease, BP- independent effect of ACE inhibitor- based regimens (about 10%)  For stroke and heart failure, no clear evidence of BP-independent effects of either ACE-I or ARB-based regimens

26 Conclusions  In active vs. active comparisons, the independent effect of ACE-I-based regimens was obscured by weaker BP lowering properties  Because of this practical limitation, therapeutic relevance is uncertain  Combination therapy with an ACE inhibitor and other BP lowering agents may offer greatest protection

27 Acknowledgements Coordinating center staff: –Fiona Turnbull MD MPH –Bruce Neal MD PhD MRCP –Charles Algert MPH –Mark Woodward PhD CStat –John Chalmers MD PhD FRACP

Download ppt "Is there evidence to justify different claims for different drug classes? Presentation to: Cardiovascular & Renal Drugs Advisory Committee Food & Drug."

Similar presentations

ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial The telmisartan trial in cardiovascular protection Sponsored by Boehringer.

ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial The telmisartan trial in cardiovascular protection Sponsored by Boehringer.
Protecting the heart and the kidney: Implications from the SHARP trial Dr. Christina Reith University of Oxford United Kingdom.

Protecting the heart and the kidney: Implications from the SHARP trial Dr. Christina Reith University of Oxford United Kingdom.
JNC 8 Guidelines….

JNC 8 Guidelines….
1 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Enalapril/ACEI vs. HCTZ, n = 6,083 Randomized, open-label (blinded endpoint review) All CV events.

1 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Enalapril/ACEI vs. HCTZ, n = 6,083 Randomized, open-label (blinded endpoint review) All CV events.
Valsartan Antihypertensive Long-Term Use Evaluation Results

Valsartan Antihypertensive Long-Term Use Evaluation Results
CVD prevention & management: a new approach for primary care Rod Jackson School of Population Health University of Auckland New Zealand.

CVD prevention & management: a new approach for primary care Rod Jackson School of Population Health University of Auckland New Zealand.
Stanford Prevention Research Center STANFORD SCHOOL OF MEDICINE National Trends in the Prescribing of Anti-Hypertensive Medications Jun Ma, MD, PhD Research.

Stanford Prevention Research Center STANFORD SCHOOL OF MEDICINE National Trends in the Prescribing of Anti-Hypertensive Medications Jun Ma, MD, PhD Research.
The ONTARGET Trial Reference The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:15.

The ONTARGET Trial Reference The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:15.
Canadian Diabetes Association Clinical Practice Guidelines Treatment of Hypertension Chapter 25 Richard E. Gilbert, Doreen Rabi, Pierre LaRochelle, Lawrence.

Canadian Diabetes Association Clinical Practice Guidelines Treatment of Hypertension Chapter 25 Richard E. Gilbert, Doreen Rabi, Pierre LaRochelle, Lawrence.
1 The JNC 7 recommendations for initial or combination drug therapy are based on sound scientific evidence.

1 The JNC 7 recommendations for initial or combination drug therapy are based on sound scientific evidence.
CHARM-Alternative: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Alternative Purpose To determine whether the angiotensin.

CHARM-Alternative: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Alternative Purpose To determine whether the angiotensin.
CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.
6 / 5 / 2006 - 1 1 RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR) ALLHAT.

6 / 5 / RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR) ALLHAT.
William B. Kannel, MD, FACC Former Director, Framingham Heart Study

William B. Kannel, MD, FACC Former Director, Framingham Heart Study
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether.
Randomized, double-blind, multicenter, controlled trial.

Randomized, double-blind, multicenter, controlled trial.
0902CZR01NL537SS0901 RENAAL Altering the Course of Renal Disease in Hypertensive Patients with Type 2 Diabetes and Nephropathy with the A II Antagonist.

0902CZR01NL537SS0901 RENAAL Altering the Course of Renal Disease in Hypertensive Patients with Type 2 Diabetes and Nephropathy with the A II Antagonist.
Is It the Achieved Blood Pressure or Specific Medications that Make a Difference in Outcome, or Is the Question Moot? William C. Cushman, MD Professor,

Is It the Achieved Blood Pressure or Specific Medications that Make a Difference in Outcome, or Is the Question Moot? William C. Cushman, MD Professor,
Systolic hypertension not an isolated problem Michael Weber, MD Professor of Medicine Associate Dean Downstate College of Medicine State University of.

Systolic hypertension not an isolated problem Michael Weber, MD Professor of Medicine Associate Dean Downstate College of Medicine State University of.
Combination Therapy for Hypertension Summary and Comment by Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology December 3, 2008Journal Watch.

Combination Therapy for Hypertension Summary and Comment by Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology December 3, 2008Journal Watch.

Similar presentations

Ads by Google