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REACH Registry: Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or with Atherothrombosis: Final Follow-Up from the International REACH Registry

Coronary Artery Disease (Chronic)

Deepak Bhatt
Presenter | see Discussant report Webcasts become avaialble 24h after the session
Bhatt, Deepak
(United States of America)
Open presentation slides

List of Authors:
Deepak L. Bhatt MD, MPH, Kim A. Eagle, MD, E. Magnus Ohman, MD, Alan T. Hirsch, MD, Shinya Goto, MD, PhD, Elizabeth M. Mahoney, PhD, Peter W. F. Wilson, MD, Mark J. Alberts, MD, Ralph D'Agostino, PhD, Chiau-Suong Liau, MD, PhD, Jean-Louis Mas, MD, Joachim Rther, MD, Sidney C. Smith, Jr., MD, Genevive Salette, Charles, F. Contant, PhD, Ph. Gabriel Steg MD, on behalf of the REACH Registry Investigators


Both clinicians and trialists struggle with identifying which patients are at highest risk of cardiovascular events. Prior ischemic events, polyvascular disease (atherothrombosis involving more than one vascular territory), and diabetes mellitus have all been identified as predictors of an elevated risk for future ischemic events, but their comparative contributions to future risk remain unclear.

Patients with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or with multiple risk factors were enrolled in the global REduction of Atherothrombosis for Continued Health (REACH) Registry and were followed for up to 4 years. Rates of cardiovascular death, myocardial infarction, and stroke were recorded.

A total of 34,436 patients with baseline data were available for analysis at 4-year follow up. Among patients with atherosclerosis, those with a history of ischemic events at baseline had the highest risk of subsequent ischemic events, patients with stable atherosclerosis had a lower risk, and patients without established atherosclerosis but with risk factors only had the lowest risk. In addition, in multivariable modeling, the presence of either diabetes or polyvascular disease significantly increased risk (P<0.0001).

Patients with atherothrombosis or with risk factors are at high cardiovascular risk. In particular, a history of ischemic events is the most powerful predictor of future ischemic events. The presence of either diabetes or polyvascular disease further increases this risk by a substantial degree. These long-term absolute event rates from this large contemporary international cohort should help in planning future clinical trials and can help clinicians identify patients at particularly high risk.

Felicita Andreotti, FESC
Discussant | see Presenter abstract Webcasts become avaialble 24h after the session
Andreotti, Felicita
Open presentation slides


A 4-year follow-up of over 28000 outpatients with stable or stabilised cardiovascular disease (CVD) reveals that polyvascular involvement or an ischaemic event within the previous year are strong predictors for the combined endpoint of CV death, myocardial infarction (MI) and stroke, each increasing the risk almost 2-fold (Table). This conclusion by Dr. Deepak Bhatt and colleagues contains several unique elements.

In 2003/4 the REduction of Atherothrombosis for Continued Health (REACH) registry started to follow a hitherto neglected and somewhat elusive population, i.e., outpatients with stabilised prior stroke or MI or with stable peripheral, coronary or carotid artery disease. Almost 6000 asymptomatic individuals with at least 3 CVD risk factors (diabetes, carotid-wall thickening or plaque, hypertension, hypercholesterolaemia, smoking, older age) were also followed. On multivariable analysis, additional age- and gender-adjusted predictors of adverse events were the presence vs absence of congestive heart failure or of diabetes and the presence of single vascular disease vs that of risk factors alone (Table).


HR (95% CI)

Polyvascular disease vs Risk factors only

1.99 (1.78-2.24)

Ischemic event ≤1 year vs No ischemic event

1.71 (1.57-1.85)

Congestive heart failure (yes/ no)

1.71 (1.60-1.83)

History of diabetes (yes/ no)

1.44 (1.36-1.53)

Ischemic event >1 year vs No ischemic event

1.41 (1.32-1.51)

Single vascular disease vs Risk factors only

1.39 (1.25-1.54)

Previous large cohort studies had longitudinally examined either initially healthy individuals over many years (e.g., Framingham and MONICA) or hospitalised patients with acute coronary syndrome (ACS) for a maximum of 1 year (e.g., GRACE and CRUSADE). Thus, REACH is the first ample long-term registry aimed at identifying predictors of hard endpoints in stabilised or stable patients with different manifestations of CVD. Other features of the REACH follow-up include its international spread in over 29 countries, and a fair female representation, although still in minority (35%).

The data presented by Dr. Bhatt point to a particular vulnerability enclosed in two aspects of CVD: the first is systemic involvement – in terms of multiple affected districts and of exhausted compensatory mechanisms (e.g.: haemodynamic in heart failure, metabolic in diabetes); the other - equally vulnerable - is the occurrence of an ischaemic event (presumably thrombotic) as opposed to a maintained stable phenotype or to asymptomatic risk factors.

In all of the prespecified REACH subgroups - with either prior ischaemia (~17000 patients), stable disease (almost 12000 patients), or risk factors alone - the incidence of CV death during follow-up approached that of nonfatal MI and nonfatal stroke combined, reinforcing the huge importance of prevention.

A question unanswered by REACH is whether or not the natural history of the risk factor only group should be considered a preclinical form of CVD. Individuals who remain asymptomatic despite the presence of 3 or more CVD risk factors may be a selected group, in some ways protected from developing symptomatic disease. Inclusion of a normal matched control arm would help redress this uncertainty.

The REACH follow-up data provide important information for long-term prognostication of CVD patients, those with extensive vascular involvement, prior ischaemia – especially if recent – or decompensated disease deserving potentially differential management strategies.


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Clinical Trial Update II
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.