Plaque regression associated with reduced MACE

In a systematic review and meta-regression analysis, a 1% reduction in atherosclerotic plaque volume (PAV) was associated with a 25% reduction in the odds of MACE compared with comparator treatment, making PAV a potential surrogate marker for CVD risk reduction.

This summary is based on the publication of Iatan I, et al. - JAMA Cardiol. 2023 Oct 1;8(10):937-945. doi: 10.1001/jamacardio.2023.2731

Introduction and methods

Background

Lipid-lowering therapies have beneficial effects on coronary plaque composition, even in patients with MI [1,2]. However, the effect of atherosclerotic plaque reduction on clinical outcomes has yet to be established [3].

Aim of the study

The study aim was to evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and the occurrence of MACE.

Methods

For this systematic review and meta-regression analysis, the authors conducted a comprehensive, systematic search of English-language articles published in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from July 2001 to July 2022. They selected 23 prospective clinical studies on lipid-lowering therapies that reported change in percent atheroma volume (PAV) or plaque volume at baseline and follow-up, as assessed by IVUS, and explicitly described the presence or absence of any component of MACE (MI, stroke, TIA, unstable angina, or all-cause mortality). The study population comprised a total of 7407 patients. Of the 23 studies, 5 were placebo-controlled and 18 included a wide range of types and doses of lipid-lowering therapies. Median follow-up duration was 44 weeks (range: 11–104).

Outcomes

The association between reported mean change in PAV and proportion of MACE at the study arm level was assessed.

Main results

• Across the 46 study arms, the mean change in PAV ranged from –5.6% (SD: 5.5%) to 3.1% (SD: 6.2%). The number of MACE ranged from 0 to 72 per study arm (0 events for 17 study arms (37%), 1–2 events for 9 study groups (20%), and ≥3 events for 20 study groups (43%)).
• In the unadjusted model, a 1% decrease in mean PAV was associated with a 17% reduced odds of experiencing MACE (0.83; 95%CI: 0.71–0.98; P=0.03).
• Multivariable analysis (with adjustment for baseline PAV, baseline LDL-c level, study duration, and age) showed a nonsignificant 14% reduction in the odds of MACE per 1% reduction in mean PAV (adjusted OR: 0.86; 95%CI: 0.75–1.00; P=0.050). After further adjustment for hypertension, diabetes, smoking, and type of patients (i.e., with stable vs. acute coronary syndrome), the OR was 0.81 (95%CI: 0.68–0.96; P=0.01).
• When only studies with both intervention and comparator arms were selected (reference group received background lipid-lowering therapy or lesser-intensity lipid treatment), a 1% reduction of PAV change between the intervention and comparator arms in individual studies was associated with a 25% reduction in the odds of MACE (OR: 0.75; 95%CI: 0.56–1.00; P=0.046).
• There was substantial heterogeneity in the association between PAV change and observed MACE across studies (χ²=193.5; P<0.001). However, the estimated intraclass correlation coefficient (2.9%) implied the contribution of interstudy variability to the overall variability was not large.

Conclusion

In this systematic review and meta-regression analysis, regression of the atherosclerotic plaque volume by 1%, as assessed by IVUS, was associated with a 25% reduction in the odds of MACE compared with comparator treatment. The authors believe their findings indicate that change in PAV has potential as a surrogate marker for CVD risk reduction, although the observed heterogeneity between studies warrants further research.

References

1. Räber L, Ueki Y, Otsuka T, et al; PACMAN-AMI Collaborators. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction. JAMA. 2022;327(18):1771-1781. doi:10.1001/jama.2022.5218
2. Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction. JACC Cardiovasc Imaging. 2022;15(7):1308-1321. doi:10.1016/j.jcmg.2022.03.002
3. Costanzo P, Perrone-Filardi P, Vassallo E, et al. Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials. J Am Coll Cardiol. 2010;56(24):2006-2020. doi:10.1016/j.jacc.2010.05.059

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