Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients


Willeit P., Tschiderer L., Allara E., Reuber K., Seekircher L., Gao L., ...More

CIRCULATION, vol.142, no.7, pp.621-642, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 142 Issue: 7
  • Publication Date: 2020
  • Doi Number: 10.1161/circulationaha.120.046361
  • Title of Journal : CIRCULATION
  • Page Numbers: pp.621-642
  • Keywords: cardiovascular disease, carotid intima-media thickness, clinical trials as topic, surrogate marker, meta-analysis, BASE-LINE CHARACTERISTICS, TYPE-2 DIABETES-MELLITUS, IMPAIRED GLUCOSE-TOLERANCE, CORONARY-HEART-DISEASE, JAPAN STATIN TREATMENT, LDL TREATMENT STRATEGIES, EXTENDED-RELEASE NIACIN, ESTROGEN PLUS PROGESTIN, ARTERIAL-WALL THICKNESS, HIV-INFECTED PATIENTS

Abstract

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 mu m/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 mu m/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.