Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH): Design Randomized, double-blind active-control 10,462 high CV-risk hypertensive patients age 55+ yrs No history of symptomatic HF or evidence of LVEF<40% Two fixed-dose antihypertensive combinations HCTZ/benazepril (12.5-25/40 mg [ ACE force-titrated]) Amlodipine/benazepril (5-10/40 mg [ACE force-titrated]) Primary endpoint: CV mortality & morbidity Morbidity: MI, stroke, hospitalized unstable angina, resuscitated sudden cardiac death, coronary revascularization Mortality: sudden cardiac death, MI, stroke, coronary intervention, heart failure, other CV causes NOTE: The ACCOMPLISH slides from ACC may be downloaded at: http://www.theheart.org/article/852911.do Copy and paste the above link into your browser. Jamerson KA et al., Am J Hypertens 2004;17:793-801 8/20/2008

ACCOMPLISH Preliminary Results: Primary* and Secondary End Points Hazard ratio (95% CI) *Cardiovascular morbidity/mortality 0.80 (0.72–0.90) Cardiovascular morbidity/mortality (excluding coronary revascularization) 0.79 (0.68–0.92) Cardiovascular mortality 0.81 (0.62–1.06) Nonfatal MI 0.81 (0.63–1.05) Nonfatal stroke 0.87 (0.67–1.13) Hospitalization for unstable angina 0.74 (0.49–1.11) Coronary revascularization 0.85 (0.74–0.99) Resuscitation for sudden death 1.75 (0.73-4.17) Jamerson KA, et al. March 31, 2008; Chicago, IL. http://www.theheart.org/article/852911.do 8/20/2008

Perspective May be promoted by some to encourage use of CCBs over thiazide-type diuretics (each with RAS inhibitors). Calls for guidelines changes are premature. Dose of thiazide-type diuretic – Doses of thiazide-type diuretics equivalent to <25-50 mg/day HCTZ have not been evaluated in clinical outcome trials demonstrating the benefits of HCTZ on CVD outcomes Data on HF not provided for ACCOMPLISH In ALLHAT, adequate dosage of diuretic was superior to both the CCB and ACE-inhibitor in preventing HF and unsurpassed for other CVD- renal outcomes 8/20/2008