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.; ... ; PROG-IMT Proof-ATHERO Study Grp (2020)

Article / Letter to editor

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.

• cardiovascular disease
• carotid intima-media thickness
• clinical trials as topic
• surrogate marker
• meta-analysis

• All authors: Willeit, P.; Tschiderer, L.; Allara, E.; Reuber, K.; Seekircher, L.; Gao, L.; Liao, X.M.; Lonn, E.; Gerstein, H.C.; Yusuf, S.; Brouwers, F.P.; Asselbergs, F.W.; Gilst, W. van; 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.; Agtmael, M.A. van; Reiss, P.; Vonderen, M.G.A. van; Kiechl, S.; Klingenschmid, G.; Sitzer, M.; Stehouwer, C.D.A.; Uthoff, H.; Zou, Z.Y.; Cunha, A.R.; Neves, M.F.; Witham, M.D.; Park, H.W.; Lee, M.S.; Bae, J.H.; Bernal, E.; Wachtell, K.; Kjeldsen, S.E.; Olsen, M.H.; Preiss, D.; Sattar, N.; Beishuizen, E.; Huisman, M.V.; Espeland, M.A.; Schmidt, C.; Agewall, S.; Ok, E.; Asci, G.; Groot, E. de; Grooteman, M.P.C.; Blankestijn, P.J.; Bots, M.L.; Sweeting, M.J.; Thompson, S.G.; Lorenz, M.W.; PROG-IMT Proof-ATHERO Study Grp
• Date: 2020-08-18
• Journal: Circulation
• Volume: 142
• Issue: 7
• Pages: 621 - 642
• DOI: doi:10.1161/CIRCULATIONAHA.120.046361
• Link: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.046361