Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100,667 Patients
Publication date
2020-08-18
Authors
Willeit, Peter
Tschiderer, Lena
Allara, Elias
Reuber, Kathrin
Seekircher, Lisa
Gao, Lu
Liao, Ximing
Lonn, Eva
Gerstein, Hertzel C
Yusuf, Salim
Editors
Advisors
Supervisors
Document Type
Article
Metadata
Show full item recordCollections
License
taverne
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 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.
Keywords
cardiovascular disease, carotid intima-media thickness, clinical trials as topic, surrogate marker, meta-analysis, Taverne, Journal Article
Citation
Willeit, P, Tschiderer, L, Allara, E, Reuber, K, Seekircher, L, Gao, L, Liao, X, Lonn, E, Gerstein, H C, Yusuf, S, Brouwers, F P, Asselbergs, F W, van Gilst, W, Anderssen, S A, Grobbee, D E, Kastelein, J J P, Visseren, F L J, Ntaios, G, Hatzitolios, A I, Savopoulos, C, Nieuwkerk, P T, Stroes, E, Walters, M, Higgins, P, Dawson, J, Gresele, P, Guglielmini, G, Migliacci, R, Ezhov, M, Safarova, M, Balakhonova, T, Sato, E, Amaha, M, Nakamura, T, Kapellas, K, Jamieson, L M, Skilton, M, Blumenthal, J A, Hinderliter, A, Sherwood, A, Smith, P J, van Agtmael, M A, Reiss, P, van Vonderen, M G A, Kiechl, S, Klingenschmid, G, Sitzer, M, Stehouwer, C D A, Blankestijn, P J, Bots, M L & PROG-IMT and the Proof-ATHERO Study Groups 2020, 'Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk : Meta-Analysis of 119 Clinical Trials Involving 100,667 Patients', Circulation, vol. 142, no. 7, pp. 621-642. https://doi.org/10.1161/CIRCULATIONAHA.120.046361