Coronary Plaque Regression and Risk of Adverse CV Events

Quick Takes

  • Coronary atherosclerotic plaque volume reduction from a baseline 36% to 55% has the potential to be a surrogate marker for major atherosclerotic events, but given heterogeneity in this meta-regression analysis, additional data are needed.
  • Among the trials that had both treatment and comparator arms, for each 1% reduction of percent atheroma volume change between treatment groups, the odds of experiencing CV events were significant at 25%.
  • The findings provide further support for the utility of CT angiography to estimate value of new therapeutics for ASCVD.

Study Questions:

What is the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and major adverse cardiovascular events (MACE) in lipid-lowering therapy trials (LLTs)?


The association between mean change in percent atheroma volume (PAV) and MACE (myocardial infarction, stroke, transient ischemic attack, unstable angina, or all-cause mortality) was analyzed by meta-regression using mixed-effects, two-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol (LDL-C) level, and study duration. Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACE. Intervention arms included high-intensity LLT and the comparator arm was a reference group of either background LLT or lesser-intensity lipid treatment.


The meta-analysis included 23 studies published between July 2001 and July 2022, including 7,407 patients (4,023 in high-intensity intervention and 3,384 in comparator arms) and trial durations ranging from 11 to 104 weeks. The number of patients per study ranged from 35 to 1,380. Three studies were nonrandomized trials, eight acute coronary syndrome (ACS) cohorts, 10 stable coronary artery disease (CAD), and two included patients with either stable CAD or ACS. Among the 23 studies, five were described as placebo-controlled, and the remainder of LLT studies had a wide range of types, drugs, and drug doses administered. Mean (standard deviation) baseline PAV ranged from 36.0% (8.3%) to 55.2% (6.1%). Mean patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from −5.6% (5.5%) to 3.1% (6.2%). The number of MACE ranged from 0 to 72 per study arm (17 groups [37%] reported no events, nine [20%] reported 1-2 events, and 20 [43%] reported ≥3 events).

In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACE (unadjusted odds ratio [OR], 0.83; 95% confidence interval [CI], 0.71-0.98; p = 0.03), and a 14% reduction in MACE in adjusted (baseline PAV, age, duration, baseline LDL-C level) analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00; p = 0.050). Further adjustment for CV risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96; p = 0.01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACE (OR, 0.75; 95% CI, 0.56-1.00; p = 0.046).


In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACE. These findings suggest that change in PAV could be a surrogate marker for MACE, but given the heterogeneity in the outcomes, additional data are needed.


In response to my request, the principal investigator Dr. G.B. John Mancini commented that stable versus unstable plaque features were not systematically available and lesions studied were in vessels large enough with a lesion remote from any PCI vessels. That percent change in atheroma volume measured by IVUS in LLTs targeting LDL-C with varying drugs, duration, and clinical status correlates with reduction in MACE was previously reported in 17 studies.

The authors added 125 new studies (previous 1,213) in this meta-regression analysis and identified six new studies to total 23. Using many sensitivity analyses including and excluding the different clinical cohorts/factors, previous findings were supported regardless of clinical status including stable coronary heart disease and ACS. This lends support for trials of new and novel drug therapies to use change in coronary plaque volume by computed tomography (CT) angiography as a surrogate for MACE to decide the cost-value of large randomized clinical trials evaluating outcome, safety, and adverse events.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Atherosclerosis, Dyslipidemias, Primary Prevention, Tomography, X-Ray Computed, Ultrasonography

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