Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100,667 Patients
Willeit, Peter; Tschiderer, Lena; Allara, Elias; Reuber, Kathrin; Seekircher, Lisa; Gao, Lu; Liao, Ximing; Lonn, Eva; Gerstein, Hertzel C; Yusuf, Salim; Brouwers, Frank P; Asselbergs, Folkert W; van Gilst, Wiek; Anderssen, Sigmund A; Grobbee, Diederick E; Kastelein, John J P; Visseren, Frank L J; Ntaios, George; Hatzitolios, Apostolos I; Savopoulos, Christos; Nieuwkerk, Pythia T; Stroes, Erik; Walters, Matthew; Higgins, Peter; Dawson, Jesse; Gresele, Paolo; Guglielmini, Giuseppe; Migliacci, Rino; Ezhov, Marat; Safarova, Maya; Balakhonova, Tatyana; Sato, Eiichi; Amaha, Mayuko; Nakamura, Tsukasa; Kapellas, Kostas; Jamieson, Lisa M; Skilton, Michael; Blumenthal, James A; Hinderliter, Alan; Sherwood, Andrew; Smith, Patrick J; van Agtmael, Michiel A; Reiss, Peter; van Vonderen, Marit G A; Kiechl, Stefan; Klingenschmid, Gerhard; Sitzer, Matthias; Stehouwer, Coen D A; Blankestijn, Peter J; Bots, Michiel L; PROG-IMT and the Proof-ATHERO Study Groups
(2020) Circulation, volume 142, issue 7, pp. 621 - 642
(Article)
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
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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 μm/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 μm/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.
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Keywords: cardiovascular disease, carotid intima-media thickness, clinical trials as topic, surrogate marker, meta-analysis, Journal Article
ISSN: 0009-7322
Publisher: Lippincott Williams & Wilkins
Note: Publisher Copyright: © 2020 American Heart Association, Inc.
(Peer reviewed)