Clinical trial NCT00251576: Aggrastat to Zocor (AtoZ) - the Use of Two Approved Drugs to Treat Patients Who Have Experienced Chest Pain or a Heart Attack (0733-180)
Official title: A Multicenter, Randomized, Controlled, Double-Blind Trial to Investigate the Clinical Efficacy and Tolerability of Early Treatment With Simvastatin 40 mg Daily for 30 Days, Followed by Simvastatin 80 mg Daily Thereafter in Tirofiban-Treated Acute Coronary Syndrome Patients Who Have Been Randomized to Receive Enoxaparin or Unfractionated Heparin in Conjunction With Aspirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndrome
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2005-11-10
Enrollment: 4497
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A-Phase: Evaluating patients with chest pain who are receiving approved drugs, to estimate the effectiveness of one type of blood thinner as compared to another type of blood thinner.

Z-Phase: To evaluate early treatment of patients with long term chest pain (using an approved drug for 30 days, followed by an increased dose of the drug) as compared to patients (treated with diet and 4 months placebo followed by diet and approved drug) in patients who have experienced acute chest pain or heart attack.


Eligibility criteria: Inclusion Criteria:

* A-Phase: Chest pain at rest for 10 minutes, EKG changes or elevated cardiac blood work
* Z-Phase: elevated cholesterol , plus at least one risk factor ( \> 70 years old, diabetes, history of prior heart or blood vessel disease, chest pain with EKG changes, elevation of cardiac lab work or positive cardiac tests , at least 2 heart vessels blocked \[one \>= 75% and one \>= 50%\])

Exclusion Criteria:

* A-Phase: use of some specific cardiac drugs, high risk bleeding, prior blood clotting disorders
* Z-Phase: elevation in certain cardiac blood tests, no significant heart damage at catheterization, planned cardiac surgery or specific cardiac drugs that lower cholesterol levels, within 6 weeks of enrollment

Primary outcomes:
measure: Z-Phase: combined frequency of the following clinical endpoint events: cardiovascular death, MI, readmission for ACS.
Secondary outcomes:
measure: Z-Phase: the incidence of the following endpoints, evaluated individually and as a composite: cardiovascular death, MI, readmission for ACS, coronary revascularization due to documented ischemia and non-hemorrhagic stroke.
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: de Lemos JA, Blazing MA, Wiviott SD, Brady WE, White HD, Fox KA, Palmisano J, Ramsey KE, Bilheimer DW, Lewis EF, Pfeffer M, Califf RM, Braunwald E; Investigators. Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial. Eur Heart J. 2004 Oct;25(19):1688-94. doi: 10.1016/j.ehj.2004.06.028.
citation: de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, Rouleau JL, Pedersen TR, Gardner LH, Mukherjee R, Ramsey KE, Palmisano J, Bilheimer DW, Pfeffer MA, Califf RM, Braunwald E; Investigators. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004 Sep 15;292(11):1307-16. doi: 10.1001/jama.292.11.1307. Epub 2004 Aug 30.
citation: Morrow DA, de Lemos JA, Sabatine MS, Wiviott SD, Blazing MA, Shui A, Rifai N, Califf RM, Braunwald E. Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation. 2006 Jul 25;114(4):281-8. doi: 10.1161/CIRCULATIONAHA.106.628909. Epub 2006 Jul 17.
citation: Wiviott SD, de Lemos JA, Cannon CP, Blazing M, Murphy SA, McCabe CH, Califf R, Braunwald E. A tale of two trials: a comparison of the post-acute coronary syndrome lipid-lowering trials A to Z and PROVE IT-TIMI 22. Circulation. 2006 Mar 21;113(11):1406-14. doi: 10.1161/CIRCULATIONAHA.105.586347. Epub 2006 Mar 13.
citation: de Lemos JA, Wiviott SD, Murphy SA, Blazing MA, Lewis EF, Califf RM, Pfeffer MA, Braunwald E. Evaluation of the National Cholesterol Education Program Adult Treatment Panel III algorithm for selecting candidates for statin therapy: insights from the A to Z trial. Am J Cardiol. 2006 Sep 15;98(6):739-42. doi: 10.1016/j.amjcard.2006.03.060. Epub 2006 Jul 26.
citation: Morrow DA, de Lemos JA, Blazing MA, Sabatine MS, Murphy SA, Jarolim P, White HD, Fox KA, Califf RM, Braunwald E; Investigators. Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease. JAMA. 2005 Dec 14;294(22):2866-71. doi: 10.1001/jama.294.22.2866.
citation: Morrow DA, Wiviott SD, White HD, Nicolau JC, Bramucci E, Murphy SA, Bonaca MP, Ruff CT, Scirica BM, McCabe CH, Antman EM, Braunwald E. Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38: an application of the classification system from the universal definition of myocardial infarction. Circulation. 2009 Jun 2;119(21):2758-64. doi: 10.1161/CIRCULATIONAHA.108.833665. Epub 2009 May 18.