High CV risk from multiorgan vascular disease blind to geographic boundaries

March 20, 2007

Chicago, IL - A prospective registry of patients from around the world has demonstrated what has long seemed apparent, that coronary artery, cerebrovascular, and peripheral arterial disease (CAD, CVD, and PAD) are widespread and a major source of morbidity and mortality without regard to international borders[1]. In particular, the >68 000-patient Reduction of Atherothrombosis for Continued Health (REACH) registry not only shows high rates of death and CV events associated with each form of vascular disease, it underscores how often they coexist and how far the risk climbs when they do.

The registry's findings from patients with established vascular disease or multiple risk factors suggest that "continued efforts are needed to improve secondary prevention and clinical outcomes," including initiatives to improve the application of evidence-based guidelines, according to the authors, Dr P hilippe Gabriel Steg (Hôpital Bichat-Claude Bernard, Paris, France) and colleagues.

The findings also indicate that "atherothrombosis should be addressed as a global arterial disease in patients," the group writes in their report on the registry's one-year outcomes, published in the March 21, 2007 issue of the Journal of the American Medical Association.

As covered at the time by heart wire , Steg had presented REACH's one-year findings in preliminary form at the American College of Cardiology 2006 Scientific Sessions.

"The REACH registry is unique because of its particularly large sample size, its international scope, and the identification of participants from physician office practices. The latter characteristic increases the generalizability of study findings to patients routinely encountered by practicing physicians," writes Dr Mary McGrae McDermott (Northwestern University, Chicago, IL) in an accompanying editorial[2]. "The REACH registry may represent a novel approach for epidemiological research with the ability to collect data rapidly on tens of thousands of study participants."

It suggests that about one in seven patients with established atherosclerotic disease will experience a major CV event, be hospitalized for CV disease, or undergo revascularization during the first year of follow-up, McDermott observes. The findings reflect "an astounding rate of costly and potentially debilitating events among individuals with chronic cardiovascular disease around the world."

REACH entered outpatients with CAD, CVD, or PAD or at least three major risk factors for vascular disease who were being treated at 5587 physician practices in 44 countries over a six-month period ending in mid-2004.

With one-year outcomes available for about 95% of the cohort, the REACH data show:

  • At least a doubling in the rate of CV death, MI, or stroke for patients with any established vascular disease compared with multiple risk factors only: 4.7% and 2.1%, respectively.

  • The rate ranged from 4.5% to 6.5% for patients with CAD, CVD, or PAD regardless of other organ-system involvement and rose to 9.2%, for patients with vascular disease in all three organ systems.

  • With the inclusion of hospitalization for atherothrombotic events in the composite end point, the rates rose to 15.2%, 14.3%, and 21.1% for CAD, CVD, and PAD, respectively. The rate reached 26.3% for patients with disease in all three systems.

Age- and sex-adjusted one-year outcomes for patients with established vascular disease at one or more sites
Parameter Any 1 system CAD alone CVD alone PAD alone CAD + CVD CAD + PAD CVD + PAD CAD, CVD, + PAD 2 or 3 systems
n 42 716 28 867 10 603 3246 5339 3264 939 1132 10 674
All-cause mortality (%) 2.45 2.42 2.55 2.39 3.61 4.58 3.58 5.37 4.08
CV death, MI, or stroke (%) 4.07 3.64 5.54 3.06 7.35 5.54 7.76 9.21 7.05
CV death, MI, stroke, or admission for TIA, unstable angina, or PAD (%) 12.6 13.0 9.87 17.4 19.8 23.1 21.9 26.3 21.7
  • Coronary revascularization, usually PCI, was performed in about 5% of patients with CAD whether or not there was other vascular disease. The corresponding rates were about 1% for carotid interventions and 9% for peripheral-vascular interventions among patients with CVD and PAD, respectively.

  • The age- and sex-adjusted rate of CV death, MI, or stroke ranged from 3.1% in Australia to 7.6% in Eastern Europe. Japan generally had the lowest end-point rates, although its nonfatal stroke rate was higher than average and above that of Australia, North America, and Western Europe.

  • Of the approximately 14 400 patients for whom employment data were available at baseline, half were no longer working after one year.

"The REACH registry demonstrates that the cardiovascular disease epidemic remains a critical and urgent international public-health problem," according to McDermott. Although the study has important limitations, including the potential for selection bias favoring sicker patients, she writes, its data show there are still major challenges to preventing CV events and related disability in patients with recognized disease despite the considerable advances in knowledge and therapy.

Baseline features, medication use, and age- and sex-adjusted one-year outcomes by geographic region

Parameter Total North America Latin America Western Europe Eastern Europe Middle East Asia Australia Japan
n 64 977 25 999 1835 17 142 5622 840 5671 2847 5021
Diabetes (%) 43.9 50.6 44.0 39.1 27.6 52.4 47.3 30.3 45.8
Hypertension (%) 81.7 86.4 78.0 79.1 83.7 80.7 79.0 77.6 70.9
Hypercholesterolemia (%) 72.0 82.7 61.5 72.3 55.1 82.4 61.0 77.6 46.4
BMI >30 (%) 29.8 41.5 23.9 28.1 28.9 29.9 8.82 29.2 4.00
ACE inhibitors (%) 45.2 47.1 42.7 45.9 72.8 54.1 32.4 42.1 18.1
Beta blockers (%) 47.5 50.6 39.1 50.6 63.2 59.9 40.5 37.3 18.6
All-cause mortality (%) 2.58 2.51 3.30 2.68 3.63 3.07 2.95 2.40 1.48
The REACH registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation of Tokyo. Disclosures for individual authors are included in the report. McDermott reports that she has received honoraria from Bristol-Myers Squibb , Sanofi-Aventis, NicOx, and Otsuka Pharmaceutical and that she has consulted for Hutchinson Technology.


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