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Research Snapshots – Dec. 7, 2011

Vulnerable Plaques: Progress Toward a Paradigm?

This Research Snapshot is based on a Technical Brief created for the Agency for Healthcare Research and Quality’s Effective Health Care Program. Technical Briefs are general overviews of new or emerging clinical interventions or health care services. Usually, there are limited published data or protocol-driven studies to permit conclusions about these interventions or services, despite public and clinician interest.

Medical interventions or technologies reviewed in Technical Briefs are nominated by the public. This summary is intended to highlight the findings and issues identified in the full report, and does not represent an endorsement of particular interventions or technologies by the Agency for Healthcare Research and Quality.

Table of Contents

The need to predict and prevent acute cardiovascular events

Acute cardiovascular events—heart attack, sudden cardiac death, or stroke—are often precipitated by an arterial occlusion when a blood clot forms at the site of an atherosclerotic plaque. According to the American Heart Association, more than 100 million people experienced an acute cardiovascular event in 2010, costing more than 150 billion dollars in related healthcare costs.

What converts any particular existing plaque into the culprit of a cardiovascular emergency is not known. The concept of “vulnerable plaques” was proposed 20 years ago, with the hypothesis that there is a characteristic or set of characteristics of some plaques that makes them susceptible to rupture, leading to deadly blood clots. If research can support this idea, then clinicians may be able to both predict and prevent heart attacks and strokes in some patients.  For more information...

Snapshot of the research

Twelve longitudinal studies since a 2004 report have investigated plaques in both coronary and carotid arteries. However, a standard definition or set of characteristics still remains elusive. Even the original definition (a plaque that is likely to rupture) has proven insufficient upon further study—some plaques rupture and heal without causing a cardiovascular event, and others that are known to be responsible for an event are not ruptured.

There is some progress toward a definition. More than one study has associated increased cardiovascular event risk with:

  • Plaques containing at least one of the proposed vulnerability features.
  • The presence of multiple suspect plaques.
  • Plaques with a larger lipid core.

But to date, nearly all studies have been conducted in patients who have already suffered a cardiovascular event. None of the proposed criteria, histological markers, serum biomarkers, or imaging features have yet been validated as predictive characteristics in any patient group.

Emerging issues

Even though the concept of vulnerable plaque remains under investigation, drug treatments that are available for existing cardiovascular indications have been evaluated for risk reduction in patients with putative vulnerable plaques. None have been cleared by the United States Food and Drug Administration for the specific indication of vulnerable plaque.

  • Statins
  • Multiple risk factor intervention (advice on smoking cessation and optimal lipid levels and metabolic control in diabetics)
  • Omega-3 and omega-6 polyunsaturated fatty acids
  • Peroxisome proliferator-activated receptor-gamma (PPAR-g) agonists
  • Oral lipoprotein-associated phospholipase A2 inhibitor (darapladib).

For more information...

Future findings

Ultimately, large prospective studies that include patients with putative vulnerable plaques, but without prior cardiovascular events, are needed to determine whether screening and treatment for vulnerable plaques will lead to improved long-term outcomes. For more information...


Alsheikh-Ali A, Kitsios GD, Balk E, Mahoney A, Lau J, Ip S. Vulnerable Atherosclerotic Plaque. Technical Brief No. 3 (Prepared by Tufts Evidence-based Practice Center under Contract No. HHSA-290-02-0022-EPC II.) AHRQ Publication No. 10-EHC062-EF. Rockville, MD: Agency for Healthcare Research and Quality. August 2010.

This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine in Houston, TX.