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KEY POINTS - Southern Medical Association

KEY POINTS - Southern Medical Association

ACCOMPLISH: Design •

ACCOMPLISH: Design • N=11,506 high CV-risk hypertensives, age ≥55 years, SBP ≥160 mm Hg or on antihypertensive Rx, 60% diabetic, 23% post MI, 36% post coronary revascularization, 13% post stroke • No history of symptomatic HF or evidence of LVEF

Does Blocking the Renin Angiotensin System (RAS) at Multiple Levels Lead to Complementary or Overlapping Effects? Non-renin (eg tPA) Angiotensinogen Renin Angiotensin I Bradykinin Non-ACE (eg chymase) ACE Angiotensin II Inactive peptides ARB AT 1 AT2 AT n Adapted from Hypertension Online Website. http://www.hypertension-online.com Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) • N=25,620; patients aged ≥55 years with CHD, PAD, CVD, or DM with endorgan damage • Patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage • Randomized, double-blind, placebo-controlled trial with patients receiving either: – Telmisartan 80 mg once daily or – Ramipril 10 mg once daily or – Telmisartan 80 mg + ramipril 10 mg once daily • Follow-up visits occurred at 6 weeks, and every 6 months thereafter • Endpoints – Primary: Composite of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure – Secondary: • Death from cardiovascular causes, myocardial infarction, or stroke (Hope Trial Endpoint) • Heart failure, diabetes mellitus, atrial fibrillation, dementia, or cognitive decline, nephropathy, and revascularization procedures ONTARGET Investigators. NEJM. 2008;358:1547-59. Key Baseline Characteristics Ramipril Telmisartan Combination N 8576 8542 8502 Age 66.4 66.4 66.5 % females 27.2 26.3 26.5 % CAD 74.4 74.5 74.7 % Stroke/TIA 21.0 20.6 20.9 % Diabetes 36.7 38.0 37.9 BP 141.8/82.1 141.7/82.1 141.9/82.1 Statins 61.0 62.0 61.8 Antiplatelet 80.5 81.1 81.1 -blocker 56.5 56.9 57.4 ONTARGET Investigators. NEJM. 2008;358:1547-59. ONTARGET: Reductions in BP by 6 Weeks of Therapy Patient population Patients randomized to ramipril (n=8576) Patients randomized to telmisartan (n=8542) Patients randomized to combination (n=8502) The ONTARGET Investigators. N Engl J Med. 2008;358:1547-1559. Baseline BP (mm Hg) BP reductions by 6 weeks (mm Hg) 141.8/82.1 -6.4/4.3 141.7/82.1 -7.4/5.0 141.9/82.1 -9.8/6.3 ONTARGET: Kaplan-Meier for Primary End Point* Primary Outcome Cumulative hazard ratio 0.20 0.15 0.10 0.05 Telmisartan Ramipril Telmisartan plus ramipril 0.00 0 1 2 3 4 5 Years of follow-up No. at risk: Telmisartan 8542 8177 7778 7420 7051 1687 Ramipril 8576 8214 7832 7472 7093 1703 Telmisartan 8502 8133 7738 7375 7022 1718 plus ramipril *The primary end point was a composite of death from CV causes, MI, stroke, or hospitalization for HF. The ONTARGET Investigators. N Engl J Med. 2008;358:1547-1559. Occurrence: Ramipril Group 1412 patients (16.5%) Telmisartan Group 1423 patients (16.7%) Combination Group 1386 patients (16.3%) ONTARGET: Adverse Effects of Telmisartan, Ramipril, or Both • Telmisartan vs ramipril: – Cough: 1.1% vs 4.2% (P

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