1 / 43

ACE vs ARB MetS/T2DM/HBP

ACE vs ARB MetS/T2DM/HBP. Mario L Maiese DO FACC FACOI Associate Professor UMDNJSOM SJHG www.sjhg.org maiese1@comcast.net EROC April 1, 2005. Goals of Presentation:. Understand the detrimental effects of AII. Understand the beneficial effects of AII blockade.

farren
Download Presentation

ACE vs ARB MetS/T2DM/HBP

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. ACE vs ARBMetS/T2DM/HBP Mario L Maiese DO FACC FACOI Associate Professor UMDNJSOM SJHG www.sjhg.org maiese1@comcast.net EROC April 1, 2005

  2. Goals of Presentation: • Understand the detrimental effects of AII. • Understand the beneficial effects of AII blockade. • Evaluate therapeutic options

  3. Effects of Angiotensin II/HBP on the Heart

  4. Renin-Angiotensin-Aldosterone System (RAAS): Detrimental effects Angiotensinogen Renin Angiotensin I Angiotensin Converting Enzyme (ACE) Angiotensin II Aldosterone AT I receptor Vascular remodeling Vasoconstriction LV remodeling Oxidative Stress Cell Growth Proteinuria

  5. Beneficial Effects

  6. Atherothrombosis

  7. Health Outcomes Prevention Evaluation (HOPE) Study:22% CV Risk Reduction Ramipril Benefit Beyond Standard Risk Reduction Therapies Alone • Diuretics • Calcium channel blockers • Aspirin and other antiplatelets • Beta-blockers • Lipid-lowering agents Composite Outcome Nonfatal MI All-Cause Mortality* CV Death Stroke 0 -5 -10 -15 % Relative Risk Reduction 16% P=0.005 -20 20% P=0.0003 22% P=0.0001 -25 26% P=0.0002 -30 *Secondary end point -35 32% P=0.0002 The HOPE Study Investigators. N Engl J Med. Jan 20 2000;342:145-153.

  8. HOPE for Patients with Diabetes MICRO-HOPE • Substudy of HOPE focusing on microalbuminuria, cardiovascular, and renal outcomes in patients 55 or older with diabetes • Study objective: To assess whether the addition of ramipril to the current medical regimens of high-risk patients with diabetes can reduce the risk of CV events • 97% of the patients in MICRO-HOPE had T2DM Data from: HOPE Study Investigators. Lancet. 2000;355:253-259.

  9. 0.20 25% Reduction in Events P = 0.0004* Placebo 0.15 Ramipril Proportion of Patients Reaching End Points 0.10 16% Reduction in Events at 1 Year 0.05 0 0 500 1,000 1,500 Days of Follow-Up MICRO-HOPE*: Primary Outcome Reductions in Stroke, MI, and CV Death * Trial halted early because of the highly significant risk reductions seen with ramipril. Data from: HOPE Study Investigators. Lancet 2000; 355: 253-259.

  10. • Aspirin • • Other Antiplatelet Agents • • Lipid-Lowering Agents • • Diuretics • • Beta-Blockers • • Calcium-Channel Blockers Nonfatal MI CV Death Total Mortality Stroke 0 -5 -10 -15 Risk Reduction (%) -20 22% † -25 *P = 0.0074 †P = 0.01 ‡P = 0.0001 §P = 0.0004 24% § -30 -35 33% * -40 37% ‡ MICRO-HOPE: Ramipril Significantly Reduces Cardiovascular Morbidity Ramipril Effects Beyond Baseline Therapy Data from: HOPE Study Investigators. Lancet 2000; 355: 253–259.

  11. HOPE MICRO-HOPE 40 35 37 33 30 32 25 26 24 Risk Reduction (%) 20 22 20 15 16 10 5 0 Nonfatal MI Stroke CV Death Total Mortality Effects of Ramipril: HOPE vs. MICRO-HOPE Data from: HOPE Study Investigators. Lancet. 2000;355:253-259. HOPE Study Investigators. N Engl J Med 2000; 342: 145-153.

  12. MICRO-HOPE • Only study to show improved outcomes in diabetics with A II Blockade.

  13. EURopean trial On reduction of cardiac events with Perindopril in stable CAD (EUROPA):20% CV Risk Reduction Perindopril Benefit Beyond Standard Risk Reduction Therapies Alone • Lipid-lowering agents • Aspirin and other antiplatelets • Beta-blockers Composite Outcome (CV death, MI & cardiac arrest) Nonfatal MI CV Death 0 -5 -10 -15 % Relative Risk Reduction -20 14% Non-significant 20% P=0.0003 -25 22% P=0.001 -30 *Secondary end point -35 The EUROPA Study Investigators. Lancet Sept 6 2003; 362: 782-788.

  14. ACE-Inhibitors-Standard of Care….to decrease events • Atherothrombosis (atherosclerosis + thrombosis), post MI. • LVSD/ HF • Diabetes • ?Hypertension • ? Met S

  15. ACE-Inhibitors-Standard of Care • Heart Outcomes Prevention Evaluation (HOPE) trial. • European Trial on Reduction of Cardiac events with Perindopril in Stable CAD (EUROPA). • Together 22,952 high risk patients with established vasc dx or DM randomized to ramipril 10mg or perindopril 8mg vs placebo. • RR reduction of 20% and 22% in CV death, MI, stroke or cardiac arrest. HOPE:N Engl J Med 2000; 342: 145-153. EUROPA: Lancet 2003; 362: 782-788.

  16. ACE Inhibitors

  17. Ace inhibitors have the broadest impact of any drug in CV medicine: • Reduce risk of death, MI, stroke, diabetes and renal impairment. • Benefit patients with HF or LV dysfunction, post MI, PAD, diabetes, stroke or TIA & AAA and renal dysfunction.

  18. ACE-Inhibitors-Standard of Care“WHOOPS” • Prevention of Events With Angiotensin-Converting-enzyme Inhibition trial (PEACE). • Lower risk CAD patients - most post revascularization on good risk reduction treatment (antiplatelet therapy, beta-blockers and statins) on trandopril 4mg vs placebo. • Resulted in no benefit. N Engl J Med 2004; 351; 2058-2068.

  19. Comparison to HOPE & EUROPA • The patients enrolled in PEACE were at lower cardiovascular risk (annualized all-cause mortality in the PEACE population was only 1.6%). • Normal mean serum creatinine and cholesterol levels and their average blood pressure was the level achieved after use of an ACE inhibitor in HOPE and EUROPA. • More patients in PEACE than in HOPE or EUROPA had undergone coronary revascularization (73% vs 40% and 54%, respectively). • More had received lipid-lowering therapy (70% vs 29% and 56%). and as a consequence, their cardiovascular event rate was lower than in HOPE and EUROPA. N Engl J Med 2004; 351; 2058-2068.

  20. Conclusions re PEACE • Results of PEACE were entirely consistent with HOPE and EUROPA. • Underpowered (more patients and longer follow-up needed because better treatment resulted in lower risk). • Dosages of drugs are not comparable. • Absolute benefit obtained depends on baseline risk.

  21. Medications that block the RAAS Angiotensinogen Renin Renin blockers-(Beta blockers) Angiotensin I Angiotensin Converting Enzyme (ACE) ACE-inhibitors Angiotensin II ARBs Aldosterone AT I receptor Aldosterone blockers

  22. A II BLOCKADE It is no coincidence that: • beta-blockers (renin inhibitors) • angiotensin converting enzyme--(ACE) inhibitors • angiotensin receptor blockers (ARBs) • Aldosterone blockade —all A II antagonists ↓CV and CRD risk and decrease mortality ….improve outcomes!

  23. Conclusion • Angiotensin II Blockade is good. • ACEI apparently are very effective with improved outcomes. • Always room for improvement!

  24. The Question? • Is an angiotensin receptor blocker (ARB) better then an ACEI because theoretically it would more completely block the effects of AII

  25. Blocking RAAS • Superior for risk reduction and less diabeto-genic than “older” anti-hypertensive agents • HOPE, EUROPA, ALLHAT and ANBP2 trials have all shown decreases incidence of T2DM with ACE inhibition. • Emerging evidence from the LIFE and CHARM trials have shown respective 25% and 28% reductions in the incidence of DM with ARBs. HOPE – Heart Outcomes Prevention Evaluation (Ramipril). N Engl J Med 2000; 242: 145-153. EUROPA – EURopean trial On reduction of cardiac events with Perindopril in stable CAD. Lancet 2003; 326: 782-788. ALLHAT – Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial. JAMA 2002; 288: 1981-1997. ANBP2 – Second Australian National Blood Pressure Study. N Engl J Med 2003; 348: 583-592. LIFE – Losarten Intervention for Endpoint Reduction (LIFE) Trial. J Clin Hypertension 2002; 4: 301-305. CHARM – Candesartan in Heart Failure—Assessment of Reduction of Mortality and morbidity. Lancet 2003; 326: 759-766.

  26. ACE inhibitors and ARBs • Improve insulin sensitivity • Usage in various studies have shown decreased development of T2DM • Unknown mechanism ? XX Induction of vascular insulin resistance on vsmc by A II…increased vasoconstriction, decreased NO, ED, increased inflammation, insulin resistance and increased prothrombotic state.

  27. Arguments Against ACEI • Poor tolerability - Cough 6% to 7% - Angioedema (1:1000) - Angioedema requiring hospitalization (1: 10,000)

  28. Arguments for ARBs • Beneficial in HF (CHARM & ELITE II). • Beneficial post MI and better tolerated (VALIANT & OPTIMAAL). • Shown to decrease progression of proteinuria and renal disease**. • Associated with decreased incidence of DM (LIFE & CHARM). • Not associated with cough or angioedema.

  29. ARB DATA • CHARM - Lancet 2003; 326:759-66. • ELITE II – Lancet 2000; 355: 1582-1587. • VALIANT - N Eng J Med 2003; 349: 1893-1906. • OPTIMAL – Lancet 2002; 360: 752-760. • LIFE – Hypertension 2002; 4: 301-305.

  30. Three recent studies show that ARBs can slow the progression of renal disease among patients with T2DM (with HBP and microalbuminuria). • Lewis EJ et al. Renoprotective effect of the angiotensin- receptor antagonist irbesartan in patients with nephropathy due to type II diabetes. N Enjl J Med 2001 Sep 20; 345: 852-60. • Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type II diabetes and nephropathy. N Engl J Med 2001 Sep 20; 345: 861-69. • Parving HH et al. The effect of irbesartan on development of diabetic nephropathy in patients with type II diabetes.N Engl J Med 2001 Sep 20; 345: 870-78.

  31. ARB vs ACE-I in T2DM + nephropathy • DETAIL study: comparison study with telmisartan vs enalapril. • Results: telmisartan is not inferior to enalapril in providing renoprotection in subjects with T2DM and mild nephropathy. N Engl J Med Nov 4 2004; 351: 1952-1961.

  32. Evaluation of Therapeutic Options- Criteria for Choice of Agent: • Should have proven CV morbidity and mortality benefits. • Should reduce BP over 24 hours (i.e. be long-acting) in order to reduce end-organ damage and the incidence of early morning cardiovascular events. • Should have direct protective properties on end organs, such as the heart, brain and kidney. • Should have a favorable interaction profile and of course needs be well tolerated.

  33. ACE INHIB VS ARB for HBP…Compelling Indications:

  34. Beneficial Effects of ACEI @ all stages (HBP→CAD→HF) • Immediate Hemodynamic: ↓ BP Preservation of bradykinin ↑ nitric acid ↓ superoxide production • Intermediate Fibrinolytic stabilization ↓ PAI-1 ↑ PA ↓ platelet activator • Late effects ↓ cell migration ↓ cell proliferation Plaque stabilization

  35. Who should receive ACE-inhibitors? • HF (LVEF < 40%) • CVD (CAD, PAD, carotid or cerebral vasc dx, AAA) • T2DM • Metabolic Syndrome (pre-diabetics) • CRD • HBP

  36. Conclusions • No Evidence of superiority of ARBs Over ACEI. • Should not replace comfort above efficacy and safety (ie ACEI the only agent with ↓ mortality benefit. • Cost should always be part of the equation. • ACEI are still first choice but use ARBs in all situations where ACEI cannot be tolerated… …and maybe as an add-on or in combo in patients T2DM/microalbuminuria.

  37. Optimal Treatment T2DM/MetS/HBP/microalbuminuria • ACEI-First choice; ARBs-Second - Poss consider both. • Hctz &/or Coreg • ASA • Statin • TLC • Control Sugars→ More drugs!!

More Related