Network meta-analysis of 14 RCTs shows upfront plaque modification increases minimum stent area but does not reduce MACE or TLR in calcified coronary lesions.

This study is a network meta-analysis synthesizing data from 14 randomized controlled trials involving a total of 3,671 patients. The analysis compared several upfront plaque-modification strategies against a conventional strategy (CS) for the treatment of calcified coronary lesions (CCL). The specific interventions evaluated included excimer laser coronary atherectomy (ELCA), intravascular lithotripsy (IVL), modified balloons (MBA), orbital atherectomy (OA), rotational atherectomy (RA), and rotational atherectomy combined with cutting balloons (RA plus CBA). The comparator group consisted of patients treated with a conventional strategy without these specific plaque-modification techniques. The setting of the included trials was not reported in the source data. The primary outcomes assessed were severe adverse events (SAE), defined as death, coronary perforation, or slow-flow/no-reflow, and minimum stent area (MSA). Secondary outcomes included major adverse cardiovascular events (MACE) and target lesion revascularization (TLR). The follow-up duration for the trials was not reported.

Regarding the primary outcome of severe adverse events, the analysis indicates that atherectomy-based strategies carried a higher risk of SAE compared with the conventional strategy. This increased risk was specifically driven by the slow-flow or no-reflow phenomenon. The study did not report specific absolute numbers, effect sizes, or confidence intervals for this comparison, nor did it provide p-values. For the secondary primary outcome of minimum stent area, the results demonstrated that all strategies except OA and ELCA significantly increased MSA compared with the conventional strategy. Specifically, RA plus CBA showed a mean difference of 0.93 mm² with a 95% confidence interval of 0.48 to 1.38, while IVL showed a mean difference of 0.59 mm² with a 95% confidence interval of 0.14 to 1.03. The direction of effect for these two strategies was an increase in MSA.

In terms of the secondary outcomes, the analysis found that none of the evaluated strategies reduced MACE versus the conventional strategy. Similarly, none of the strategies reduced TLR versus the conventional strategy. The study did not report specific effect sizes, absolute numbers, or confidence intervals for these negative findings regarding MACE and TLR. Safety and tolerability findings were limited; while serious adverse events were discussed in the context of the higher risk for atherectomy-based strategies, specific adverse event rates and discontinuation data were not reported. The study notes that the gain in minimum stent area did not translate into significant reductions in MACE or TLR.

When comparing these results to prior landmark studies in the therapeutic area of calcified coronary lesions, the current evidence suggests that while procedural techniques can successfully modify plaque to allow for larger stent areas, this anatomical improvement has not yet resulted in a reduction of clinical events. The study highlights that the probability of lower mortality was ranked highest for IVL, though this was not explicitly stated as a significant reduction in mortality in the provided data. Key methodological limitations include a limited number of events, a scarcity of head-to-head trials, and limited data on clinical outcomes. Additionally, the funding sources and conflicts of interest were not reported.

The clinical implications of this network meta-analysis are that upfront plaque modification improves minimum stent area compared with a conventional strategy. However, practitioners must recognize that this gain in stent expansion did not translate into significant reductions in major adverse cardiovascular events or target lesion revascularization. This suggests that the choice of plaque-modification strategy may need to be weighed carefully against the potential for increased severe adverse events, particularly slow-flow or no-reflow, without a clear benefit in hard clinical endpoints. Questions remain unanswered regarding which specific patient subgroups might derive the most benefit or which strategies offer the best risk-benefit profile when mortality is considered. The certainty of the evidence is constrained by the limitations of the underlying trials and the lack of direct comparisons between many of the strategies.