ESC Focus on Interventions & PC - 11D

Table 2. COMPASS in Context: Lipid Lowering, Blood Pressure
Lowering, and ACE
Lipid
Lowering
(1 mmol/L)

BP
Lowering
(10 mm Hg)

ACE
(HOPE)

COMPASS
Rivaroxaban
+ Aspirin

MACE (RRR %)

21%

20%

22%

24%

Death

13%

16%

18%

Stroke

15%

27%

32%

42%

24%

17%

20%

14%

ACE, angiotensin-converting enzyme; BP, blood pressure; MACE, major adverse
cardiovascular events; MI, myocardial infarction; RRR, relative risk reduction.
Sources: HOPE investigators. N Engl J Med. 2000;342:143-53; Ettehad D et al.
Lancet. 2016;387-957-67; CTT Collaboration. Lancet. 2015;385:1397-1405; Collins R et al. Lancet. 2016;388:2532-61; Eikelboom JW et al. N Engl J Med. 2017;
doi: 10.1056/NEJMoa1709118.

antiplatelet drug versus a very low dose of a factor Xa
inhibitor; second, combining a P2Y12 inhibitor or thrombin-receptor antagonist with a very low dose of a factor
Xa inhibitor, which might lead to even greater efficacy by
reducing myocardial infarction.20 He also suggested that
different subgroups of patients with chronic ischaemic
heart disease, such as those with a history of an acute
coronary syndrome or those with heart failure, will have
different responses to these various drug combinations,
and this could lead to a more personalised approach to
patients with chronic ischaemic heart disease.
References
1.

Eugene Braunwald, MD, Brigham and Women's
Hospital, Harvard Medical School, Boston, Massachusetts,
USA, put the results of the COMPASS into historical perspective and suggested how this trial might have implications for clinical practice going forward.18 Aspirin was
first established as CAD treatment a quarter century
ago. When it was discovered that platelet pathways and
coagulation pathways are both involved in coronary
arterial thrombosis,19 the combination of warfarin plus
low-dose aspirin was studied. Efficacy was maintained,
but bleeding was excessively increased compared with
aspirin alone, and this combination was not adopted.
When oral Xa inhibitors became available they were
found to interfere with thrombin-induced platelet activation as well as their expected inhibition of thrombin.
The ATLAS TIMI-51 trial established the safety and efficacy of 2.5 and 5.0 mg twice daily doses of the factor Xa
inhibitor rivaroxaban, in patients with ACS. Compared
with placebo the risk of CV death, stroke, or MI was significantly lower without a significant increase in fatal
bleeding.14
The landmark COMPASS trial has taken these findings a step further by demonstrating that vascular doses of rivaroxaban plus aspirin in patients with chronic
CAD are superior to aspirin alone as well as rivaroxaban alone without increasing major bleeding risk. Dr
Braunwald believes COMPASS is an important step in
thrombocardiology that is likely to change guidelines
for the management of chronic CAD, but he hopes this
is not the end of clinical investigation in this direction.
He offered 2 possible future studies - first, a head-tohead comparison between the aspirin plus a second

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World Health Organization. World Health Organization. Fact Sheet No. 310. 2017;
http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 31 August, 2017.
Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation.
2016;133(4):e38-360.
Sorbets E, Greenlaw N, Ferrari R, et al. Rationale, design, and baseline characteristics of the CLARIFY registry of outpatients with stable coronary artery disease.
Clin Cardiol. 2017;doi: 10.1002/clc.22730.
Steg PG. Heart rate management in coronary artery disease: the CLARIFY registry. Eur Heart J. 2009;11(Suppl_D August):D13-18.
Steg PG, Greenlaw N, Tendera M, et al. Prevalence of anginal symptoms and myocardial ischemia and their effect on clinical outcomes in outpatients with stable
coronary artery disease: data from the International Observational CLARIFY Registry. JAMA Intern Med. 2014;174(10):1651-1659.
Ohman EM, Bhatt DL, Steg PG, et al. The REduction of Atherothrombosis for Continued Health (REACH) Registry: an international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. Am Heart
J. 2006;151(4):786.e781-710.
Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis.
JAMA. 2010;304(12):1350-1357.
Steg PG, Bhatt DL, Wilson PW, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. 2007;297(11):1197-1206.
Cavender MA, Steg PG, Smith SC, Jr., et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years
from the reduction of atherothrombosis for Continued Health (REACH) Registry.
Circulation. 2015;132(10):923-931.
Bhatt DL. Advancing the care of cardiac patients using registry data: going where
randomized clinical trials dare not. JAMA. 2010;303(21):2188-2189.
Steg PG, Lopez-Sendon J, Lopez de Sa E, et al. External validity of clinical trials in
acute myocardial infarction. Arch Intern Med. 2007;167(1):68-73.
Wong YN, Mitra N, Hudes G, et al. Survival associated with treatment vs observation of localized prostate cancer in elderly men. JAMA. 2006;296(22):2683-2693.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular
atrial fibrillation. N Engl J Med. 2011;365(10):883-891.
Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent
acute coronary syndrome. N Engl J Med. 2012;366(1):9-19.
Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in
stable cardiovascular disease. N Engl J Med. 2017 DOI: 10.1056/NEJMoa1709118.
Bosch J, Eikelboom JW, Connolly SJ, et al. Rationale, design and baseline characteristics of participants in the Cardiovascular OutcoMes for People Using Anticoagulation StrategieS (COMPASS) Trial. Can J Cardiol. 2017;33(8):1027-1035.
Schulman S, Kearon C. Definition of major bleeding in clinical investigations of
antihemostatic medicinal products in non-surgical patients. J Thromb Haemost.
2005;3(4):692-694.
Braunwald E. An important step for thrombocardiology. N Engl J Med. 2017;DOI:
10.1056/NEJMe1710241.
Welsh RC, Roe MT, Steg PG, et al. A critical reappraisal of aspirin for secondary
prevention in patients with ischemic heart disease. Am Heart J. 2016;181:92-100.
Ohman EM, Roe MT, Steg PG, et al. Clinically significant bleeding with low-dose
rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet.
2017;389(10081):1799-1808.

http://www.who.int/mediacentre/factsheets/fs310/en/

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