Bringing Science to Practice: Therapy Underutilization and Compliance in CV disease - The Aspirin Perspective Aspirin underuse, poor compliance and cessation Giuseppe Biondi-Zoccai, MD Sapienza University of Rome, Latina, Italy Melbourne, May 6, 2014 – 16:00 to 19:00 - Room M14, Crown Promenade Bringing Science to Practice: Therapy Underutilization and Compliance in CV disease - The Aspirin Perspective Aspirin underuse, poor compliance and cessation Giuseppe Biondi-Zoccai, MD Sapienza University of Rome, Latina, Italy Melbourne, May 6, 2014 – 16:00 to 19:00 - Room M14, Crown Promenade

Goals of the Roundtable Prevalence of non-adherence to Aspirin Consequences of non- compliance/discontinuation to Aspirin Issues surrounding non-compliance to Aspirin Tools and programs to improve compliance to Aspirin

Too old to be good?

Too good to be true?

Do we still need Aspirin?

What are the facts?

Goals of the Presentation Underutilisation and poor adherence in secondary prevention of CVD Physician and patient perceptions about Aspirin Impact of Aspirin discontinuation (including inconsistent use and temporary discontinuation)

Updated terminology Cessation: any ceasing or discontinuance Compliance: accuracy with which a patient follows an agreed treatment plan Discontinuation: physician-supervised withdrawal as perceived as no longer needed Disruption: cessation due to non-compliance or bleeding (brief: 1-5 days; temporary: 6-30 days; permanent: >30 days) Interruption: physician-supervised temporary discontinuation for surgery lasting <15 days Underuse: act of using (or prescribing) less than expected Mehran et al, Lancet 2013;382:

Aspirin use in US secondary prevention George MG et al, MMWR Morb Mortal Wkly Rep 2012;61 Supp:11-8

Self-reported Aspirin underuse among US patients with established indication Rivera et al, J Womens Health (Larchmt) 2012;21:379-87

Aspirin compliance in Europe-Latin America Zaninelli et al, Postgrad Med 2009;121:44-53

Aspirin compliance in Asia-Pacific Zaninelli et al, Postgrad Med 2010;122:108-17

Focus on post-ACS in China: the BRIG study Niu et al, Am Heart J 2009;157: e1

Goals of the Presentation Underutilisation and poor adherence in secondary prevention of CVD Physician and patient perceptions about Aspirin Impact of Aspirin discontinuation (including inconsistent use and temporary discontinuation)

Aspirin for primary prevention in women Ridker et al, for the Women Health Study Investigators, New Engl J Med 2005;352:

Aspirin for primary prevention in men Physicians’ Health Study Investigators, New Engl J Med 1989;321:129-35

Impact on fatal/non-fatal colorectal cancer Rothwell et al, Lancet 2010;376:

Benefits vs harms Patrono et al, Eur Heart J 2013

Some remain skeptical Cleland et al, Eur Heart J 2013;34:3412-8

Differences between US and Europe Wolff et al, Ann Intern Med 2009

Differences between US and Europe Perk et al, Eur Heart J 2012

Underuse in US ambulatory care Stafford et al, PLoS Med 2005;2:e353

Causes of underuse Pignone et al, Am J Prev Med 2007;32:403-7

Non-compliance vs discontinuation Herlitz et al, Am J Cardiovasc Drugs 2010;10:125-41

Perceptions on Aspirin in Europe-Latin America Zaninelli et al, Postgrad Med 2009;121:44-53

Perceptions on Aspirin in Asia-Pacific Zaninelli et al, Postgrad Med 2010;122:108-17

Means to improve compliance Zaninelli et al, Postgrad Med 2009;121:44-53

Goals of the Presentation Underutilisation and poor adherence in secondary prevention of CVD Physician and patient perceptions about Aspirin Impact of Aspirin discontinuation (including inconsistent use and temporary discontinuation)

Ominous impact of aspirin discontinuation Biondi-Zoccai et al, Eur Heart J 2006;27:

Discontinuation after stenting Rossini et al, Am J Cardiol 2011;107:186-94

Impact DAPT discontinuation after stenting Mehran et al, Lancet 2013;382: MYOCARDIAL INFARCTION CARDIAC DEATH

Discontinuation in UK primary care Rodriguez et al, BMJ 2011;343:d4094

Discontinuation: thrombotic vs bleeding events Cea Soriano et al, Thromb Haemost 2013;110:

Avoiding discontinuation is also cheaper Cea Soriano et al, Thromb Haemost 2013;110:

Take home messages Differentiating between type, reason, setting and timing of underuse and discontinuation of Aspirin is crucial Inadequate physician-patient communication and lack of awareness of underlying cardiovascular risk and benefits are the key reasons for Aspirin underuse and discontinuation Underuse and discontinuation are clearly detrimental for patients, especially early after an acute cardiovascular event or procedure, but even later on

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Reserve slides

ASPREE ASPREE is a randomised, double-blind placebo trial of 5-year low-dose (100mg) aspirin for 5 years It involves both males and females, 70 years and older The study is recruiting 19,000 healthy participants through regional centres (both in urban and rural locations throughout Australia and the United States) The trial has a number of sub-studies, which investigate the effect of aspirin on specific diseases: Biobank, ENVIS-ion, ALSOP, SNORE-ASA, ASPREE-AMD, ASPREE-Knee, and ASPREE-NEURO Results are expected for

Aspirin: a measure of quality of care? Quality of health care according to the US Institute of Medicine: degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with professional knowledge

Aspirin discontinuation: a hot topic Biondi-Zoccai et al, BMJ 2011;343:d3942

Focus on terminology Mehran et al, Lancet 2013;382:

Delayed anti-cancer effects Burn et al, Lancet 2011;378:2081-7

Aspirin as key component of polypills Wald et al, BMJ 2003;326:1419

Compliance according to indication VanWormer et al, J Fam Pract 2012;61: *with 102 (18%) reporting aspirin use *

Some remain skeptical Sutcliffe et al, PLoS ONE 2013;8:e81970

Aspirin use in US primary prevention George MG et al, MMWR Morb Mortal Wkly Rep 2012;61 Supp:11-8

Self-reported Aspirin underuse Rivera et al, J Womens Health (Larchmt) 2012;21:379-87

Underuse in US ambulatory care Stafford et al, PLoS Med 2005;2:e353

Self-reported Aspirin underuse Rivera et al, J Womens Health (Larchmt) 2012;21:379-87

Focus on post-MI in China: the BRIG study Niu et al, Am Heart J 2009;157: e1

Aspirin compliance in Europe-Latin America Zaninelli et al, Postgrad Med 2009;121:44-53

Aspirin compliance in Asia-Pacific Zaninelli et al, Postgrad Med 2010;122:108-17

Aspirin resistance: fact or fiction? Biondi-Zoccai et al, BMJ 2008;336:166-7

Aspirin for primary prevention in men Physicians’ Health Study Investigators, New Engl J Med 1989;321:129-35

Focus on post-ACS in China: the BRIG study Niu et al, Am Heart J 2009;157: e1

Resistance or non-compliance? Schwartz et al, Am J Cardiol 2005;95:973-5

Cumulative incidence after stenting Mehran et al, Lancet 2013;382:

Means to improve compliance in Asia-Pacific Perceived as effective by most physicians: 1.Material demonstrating the lifelong benefits of Aspirin 2.Material demonstrating the immediate effects of Aspirin 3.Shared patient-physician decision-making 4.Suitable patient information Zaninelli et al, Postgrad Med 2010;122:108-17

Discontinuation after stenting Rossini et al, Am J Cardiol 2011;107:186-94

Discontinuation after stenting Rossini et al, Am J Cardiol 2011;107:186-94

Discontinuation after stenting Rossini et al, Am J Cardiol 2011;107:186-94

Discontinuation after stenting Rossini et al, Am J Cardiol 2011;107:186-94

Avoiding discontinuation is also cheaper Cea Soriano et al, Thromb Haemost 2013;110: