There is a Primary Prevent Indication in Diabetes | Mubashar A Choudry

Editor's Notes

• #4: Speaker’s Notes Please disclose any relevant financial relationships Speakers should be very clear in identifying any current or previous forms of support that they have received from granting agencies, health organizations and/or industry, etc.
• #5: Atherothrombosis is the most frequent underlying cause of ischemic heart disease and cardiovascular (CV) disease and is the leading cause of death in Western societies.1 Acute coronary syndrome (ACS) and ischemic stroke are usually caused by acute thrombosis superimposed on a chronic atherosclerotic plaque that has erupted, a condition commonly called atherothrombosis.2 Atherothrombosis is a slowly progressive, degenerative disease of the large- and middle-sized elastic and muscular arteries, beginning with fatty streak formation in adolescence. When it progresses unabated, the streaks develop into plaques, culminating in thrombotic occlusions and CV events later in life.1
• #6: Atherosclerosis is an ongoing process affecting mainly large- and medium-sized arteries; it can begin in childhood and progress throughout a person’s lifetime.1 Stable atherosclerotic plaques may encroach on the lumen of the artery and cause chronic ischemia, resulting in (stable) angina pectoris or intermittent claudication, depending on the vascular bed affected.2 Unstable atherosclerotic plaques may rupture, leading to the formation of a platelet-rich thrombus that partially or completely occludes the artery and causes acute ischemic symptoms.2,3 References 1Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation. 2001;104:365-372. 2Rauch U, Osende JI, Fuster V, et al. Thrombus formation on atherosclerotic plaques: pathogenesis and critical consequences. Ann Intern Med. 2001;134:224-238. 3Yeghiazarians Y, Braunstein JB, Askari A, et al. Unstable angina pectoris. N Eng J Med. 2000;342:101-114.
• #7: Primary hemostasis: process of platelet adhesion (a), activation (b), and aggregation (c). Platelets initiate thrombosis at the site of a ruptured plaque: the first step is platelet adhesion (a) via the glycoprotein Ib receptor in conjunction with von Willebrand factor. This is followed by platelet activation (b), which leads to a shape change in the platelet, degranulation of the alpha and dense granules, and expression of GP IIb/IIIa receptors on the platelet surface with activation of the receptor, such that it can bind fibrinogen.2 The final step is platelet aggregation (c), in which fibrinogen (or von Willebrand factor) binds to the activated GP IIb/IIIa receptors of two platelets.2 Aspirin and clopidogrel act to decrease platelet activation3 whereas the glycoprotein IIb/IIIa inhibitors inhibit the final step of platelet aggregation.2 References 1Cannon CP and Braunwald E. Heart Disease. 2001. 2Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and nonST-segment elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2000;36:970-1062. 3Cannon CP, on behalf of the Caprie Investigators. Effectiveness of clodipogrel versus aspirin in preventing acute myocardial infarction in patients with sympotomatic atherothrombosis (CAPRIE trial). Am J Cardiol. 2002;90:760-762.
• #8: Page 421, column 1, paragraph 1 Reference 1, full citation: Badimon et al. In Platelets in thrombotic and non thrombotic disorders, 1st ed., New York: Cambridge University Press, 2002, 727-737
• #12: How is 10-Year CHD Risk calculated? The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of aspirin for CVD prevention in men and women 80 years or older.
• #13: Add data on DM from: US Preventive Services Task Force Ann Intern Med 2009;150:396-404 How was DM handled in ATC?
• #19: Watch for further trials – ASCEND and ACCEPT-D – ongoing trials that enrol > 15,000 DM patients that will help clarify the role of aspirin in the primary prevent of CVD.
• #22: In order to evaluate the full body of evidence on the effectiveness of antiplatelet therapy, an updated collaborative overview of randomized trials of antiplatelet therapy among high-risk patients has been undertaken.1 This meta-analysis included all antiplatelet agent trials up until 1997, particularly new trials with ASA, clopidogrel and dipyridamole (notably the CAPRIE* trial and ESPS2†), that were not available for the previous antiplatelet trialists’ collaboration, published in 1994 (287 vs 145 trials respectively). *Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events †European Stroke Prevention Study 2
• #23: This slide compares risk reduction in a number of high-risk subgroups to the overall result, which demonstrated a consistent benefit across all patient groups with a mean of 22%.1 Stratified odds ratio of an event in treatment groups to that in control groups were plotted for each group of trials (white diamond) – along with a 99% confidence interval (horizontal line). ‘Other’ high risk groups (total reduction 13% ±7) include hemodialysis (reduction 41% ±16), diabetes mellitus (reduction 7% ±8), carotid disease (reduction 19% ±22).
• #24: The Antithrombotic Trialists’ Collaboration compared data from 65 aspirin trials to examine the effects of aspirin dose on vascular events in high-risk patients (in some trials, the aspirin dose was used in more than one of the comparisons).1 Serious vascular events (the primary measure of outcome) included nonfatal myocardial infarction, nonfatal stroke, death from vascular causes, and death from unknown causes. They found that all doses of aspirin studied reduced the risk of vascular events. The greatest number of trials (34) examined high aspirin doses (500-1500 mg) and revealed a proportional reduction in vascular events of 19%. Aspirin doses of 160 to 325 mg were associated with a 26% proportional reduction in vascular events, whereas 75 to 150 mg and <75 mg were associated with reductions of 32% and 13%, respectively.
• #26: Patients presenting with one type of atherothrombotic event are at increased risk for a second event, frequently in a different vascular territory.1 This demonstrates that once a patient manifests atherothrombotic disease, the patient is at high risk for future events. Data for the associated risk increase in events were taken from different sources,but show that the risk of a second vascular event can increase 2 to 9-fold.1 The increase in risk of events was based on a 10-year follow-up, except for the risk of stroke following stroke, which measures subsequent risk per year.1-3 References 1Kannel WB. Risk factors for atherosclerotic cardiovascular outcomes in different arterial territories. J Cardiovasc Risk. 1994;1:333-339. 2Wilterdink JI, Easton JD. Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol. 1992;49:857-863. 3Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381-386.