TY - JOUR
T1 - Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients
T2 - Meta-Analysis of 119 clinical trials involving 100 667 patients
AU - PROG-IMT and the Proof-ATHERO Study Groups
AU - Willeit, Peter
AU - Tschiderer, Lena
AU - Allara, Elias
AU - Reuber, Kathrin
AU - Seekircher, Lisa
AU - Gao, Lu
AU - Liao, Ximing
AU - Lonn, Eva
AU - Gerstein, Hertzel C.
AU - Yusuf, Salim
AU - Brouwers, Frank P.
AU - Asselbergs, Folkert W.
AU - van Gilst, Wiek
AU - Anderssen, Sigmund A.
AU - Grobbee, Diederick E.
AU - Kastelein, John J. P.
AU - Visseren, Frank L. J.
AU - Ntaios, George
AU - Hatzitolios, Apostolos I.
AU - Savopoulos, Christos
AU - Nieuwkerk, Pythia T.
AU - Stroes, Erik
AU - Walters, Matthew
AU - Higgins, Peter
AU - Dawson, Jesse
AU - Gresele, Paolo
AU - Guglielmini, Giuseppe
AU - Migliacci, Rino
AU - Ezhov, Marat
AU - Safarova, Maya
AU - Balakhonova, Tatyana
AU - Sato, Eiichi
AU - Amaha, Mayuko
AU - Nakamura, Tsukasa
AU - Kapellas, Kostas
AU - Jamieson, Lisa M.
AU - Skilton, Michael
AU - Blumenthal, James A.
AU - Hinderliter, Alan
AU - Sherwood, Andrew
AU - Smith, Patrick J.
AU - van Agtmael, Michiel A.
AU - Reiss, Peter
AU - van Vonderen, Marit G. A.
AU - Kiechl, Stefan
AU - Klingenschmid, Gerhard
AU - Sitzer, Matthias
AU - Stehouwer, Coen D. A.
AU - de Groot, Eric
AU - Grooteman, Muriel P. C.
AU - Uthoff, Heiko
AU - Zou, Zhi Yong
AU - Cunha, Ana R.
AU - Neves, Mario F.
AU - Witham, Miles D.
AU - Park, Hyun Woong
AU - Lee, Moo Sik
AU - Bae, Jang Ho
AU - Bernal, Enrique
AU - Wachtell, Kristian
AU - Kjeldsen, Sverre E.
AU - Olsen, Michael H.
AU - Preiss, David
AU - Sattar, Naveed
AU - Beishuizen, Edith
AU - Huisman, Menno V.
AU - Espeland, Mark A.
AU - Schmidt, Caroline
AU - Agewall, Stefan
AU - Ok, Ercan
AU - Aşçi, Gülay
AU - Blankestijn, Peter J.
AU - Bots, Michiel L.
AU - Sweeting, Michael J.
AU - Thompson, Simon G.
AU - Lorenz, Matthias W.
PY - 2020/8/18
Y1 - 2020/8/18
N2 - 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.
AB - 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.
KW - cardiovascular disease
KW - carotid intima-media thickness
KW - clinical trials as topic
KW - meta-analysis
KW - surrogate marker
UR - http://www.scopus.com/inward/record.url?scp=85089708643&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCULATIONAHA.120.046361
DO - https://doi.org/10.1161/CIRCULATIONAHA.120.046361
M3 - Article
C2 - 32546049
SN - 0009-7322
VL - 142
SP - 621
EP - 642
JO - Circulation
JF - Circulation
IS - 7
ER -