PracticeUpdate Cardiology March 2019

TOP STORIES 2018 5

Aspirin Primary Prevention Trials By Joerg Herrmann MD

Aspirin is an integral component of secondary prevention guidelines for patients with established cardiovascular diseases (CVD). Based results of meta-analyses, such as the ones by the Antithrombotic Trialists’ Collaboration over a decade ago, it reduces the risk of myocardial infarction (MI), stroke, and vascular death by 35%, 25%, and 15%, respectively. Following stroke and MI, the use of aspirin leads to 36 fewer events of recurrent MI, stroke, or vascular death per 1000 patients treated, outweighing the risk of 1 to 2 major bleeds per 1000 patients treated.

I n 2016, two systematic reviews/ meta-analyses conducted by the US Preventive Services Task Force (USP- STF) indicated that the efficacy of primary prevention with aspirin may be of the same magnitude, a 20% risk reduction, at a nearly 60% higher risk of major bleeding events and a 30% higher risk of hemorrhagic stroke. 1,2 A second systematic review further- more concluded on a 20% to 24% reduction in the incidence of colorectal cancer (CRC) and a 33% reduction in CRC mortality. These data fueled the grade B USPSTF recommendation for low-dose aspirin for primary prevention of CVD and CRC in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. For those aged 60 to 69 years with similar characteristics, the decision was to be an individual one. No recommendations could be given for those outside these age ranges. The 2012 American College of Chest Physicians evi- dence-based clinical practice guidelines suggest low-dose aspirin for primary pre- vention for individuals aged 50 and older. 3 The 2002 American Heart Association pri- mary prevention guidelines recommended the consideration of low-dose aspirin in persons at higher risk (especially those with 10-year CVD risk of 10%). 4 On the contrary, the 2016 European Society of Cardiology primary prevention guidelines recom- mended against it (class III). 5 Hence, not much of a surprise, there has been consid- erable uncertainty whether to pursue or not pursue aspirin for the purpose of primary prevention of CVD (and CRC).

In 2018, three randomized clinical trials pro- vided an answer to this pressing question. The three trials were ASCEND in diabetics, ARRIVE in patients at moderate calculated CV risk (an approximate 15% 10-year risk), and ASPREE in patients aged 70 years or older. 6-8 All three trials compared low- dose aspirin (100 mg daily) with placebo over 5 (ARRIVE and ASPREE) to 7.5 years (ASCEND), and their collective findings are as following: 1. no difference in MI and stroke rates; 2. no difference in CV mortality; 3. no difference in all-cause mortality in ASCEND and ARRIVE, and a small increase in risk with aspirin in ASPREE; and 4. higher risk of gastrointestinal malignancy among aspirin users in the ASPREE trial and a numerically higher but still overall small risk with aspirin in the ARRIVE trial. This is a “three strikes out” scenario for primary prevention aspirin all in a single year. Undoubtedly, the ASCEND, ARRIVE, ASPREE trial trio has changed the land- scape in preventive cardiology forever. These results are reinforcing some, while challenging a re-write of other, guidelines as much as they most likely will influence practice directly. When patients ask, or are confronted with the question in other ways, providers now know how to respond. The answer is found in three randomized con- trolled trials carefully conducted in nearly 50,000 patients across a wide range of possible scenarios that might have justi- fied primary prevention aspirin in the past, but no longer will – 2018, a major game changer, if you will.

References 1. Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2016;164(12):836-845. 2. Dehmer SP, Maciosek MV, Flottemesch TJ, et al. Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2016;164(12):777-786. 3. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012 Feb;141(2 Suppl):e637S-e668S. 4. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002 Jul 16;106(3):388-391. 5. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37(29):2315-2381. 6. ASCEND Study Collaborative Group, Bowman L, MafhamM, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379(16):1529-1539. 7. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo- controlled trial. Lancet 2018;392(10152):1036-1046. 8. McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379(16):1509-1518. www.practiceupdate.com/c/76724

VOL. 4 • NO. 1 • 2019