Moderate/Severe Calcification in ACS Patients Linked to Worse Post-PCI Outcomes

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A pooled analysis of 2 large randomized trials found that moderate to severe lesion calcification is relatively common in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). The paper, published online February 19, 2014, ahead of print in the Journal of the American College of Cardiology, found that lesion calcification is strongly predictive of stent thrombosis and ischemic target lesion revascularization (TLR) at 1 year.

Researchers led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), looked at 6,855 PCI patients presenting with either STEMI or NSTE ACS from the HORIZONS-AMI (n = 3,268) and ACUITY (n = 3,587) randomized trials. Quantitative coronary angiography was performed by an independent core laboratory.

There were a total of 8,381 target lesions, of which 5.4% were deemed heavily calcified, 25.5% were moderately calcified, and 69.1% had no or mild calcification. Target lesion calcification was more frequent among STEMI patients than NSTE ACS patients. On multivariable analysis, older age, male gender, history of hypertension, and STEMI presentation were independent predictors of moderate/severe target lesion calcification (table 1).

Table 1. Independent Predictors of Moderate/Severe Target Lesion Calcification

PCI in patients with moderately and severely calcified lesions was associated with higher unadjusted 1-year rates of adverse events (table 2).

Table 2. Outcomes at 1 Year by Calcification Severity

^aMACE: death, reinfarction, ischemic revascularization.

On multivariable analysis, PCI of moderate/severe calcification was independently associated with higher 1-year rates of definite stent thrombosis (HR 1.62; 95% CI 1.14-2.30; P = 0.007) and ischemic TLR (HR 1.44; 95% CI 1.17-1.78; P = 0.0007), but not increased death or MI.

Many Contributing Factors

Dr. Stone and colleagues list several mechanisms that may explain the poor outcomes after PCI of calcified lesions:

• Stent underexpansion is frequent in heavily calcified lesions and may increase the risk for restenosis and stent thrombosis
• Difficulty in delivering stents may lead to structural device damage and polymer tearing in DES, which may create a prothrombotic environment and promote neointimal proliferation
• An established relationship between the severity of calcification and thrombogenicity
• The association of several genetic loci with the development of both vascular calcification and clinical events

The investigators postulate that the presence of coronary calcification may be a marker of poorer outcome and not the entire cause. Thus, “it is possible that even if technical advances were to obviate the negative consequences of calcification itself, the outcomes of these patients may still be worse,” they caution.

Because the trial patients were treated with BMS (20%) and first-generation DES (80%), the authors suggest that use of contemporary devices may alter the results. “However, whether second-generation DES perform better in severely calcified lesions has yet to be demonstrated,” they say.

In an accompanying editorial, David D. Waters, MD, of the University of California, San Francisco School of Medicine (San Francisco, CA), and Rabih R. Azar, MD, MSc, of the Saint-Joseph University School of Medicine (Beirut, Lebanon), write that the authors “have done us a service by highlighting the continuing bad consequences of [target lesion calcification]. Despite huge advances in PCI technology over nearly 50 years, the curse of calcification persists.”

New Device May Change Perception of Calcification

Jeffrey W. Chambers, MD, of the Metropolitan Heart and Vascular Institute (Minneapolis, MN), told TCTMD in a telephone interview that despite the longtime knowledge that calcification makes lesions harder to treat, there has been a paucity of treatment options. Though rotational atherectomy has been available for a while, it “hasn’t really shown long-term benefits compared to stenting alone.”

However, a device recently approved by the US Food and Drug Administration might change how clinicians view this complication, he said. The Diamondback 360ᴼ orbital atherectomy system (Cardiovascular Systems, St. Paul, MN), which uses a rotating, eccentric diamond-coated crown to remove the hard components of plaque while leaving the soft components untouched, showed good results in the ORBIT II trial presented in May 2013 at EuroPCR in Paris, France.

“Now that we have some more potential treatment options, people are going to start to reexamine what it means to treat these calcified lesions and then [determine if there is] something we can do to prevent these adverse outcomes,” Dr. Chambers observed.

Drs. Waters and Azar suggest that another option might be “the use of more potent antiplatelet drugs such as prasugrel or ticagrelor instead of clopidogrel . . ., although this has not been proven.”

Study Details

Compared with patients without calcified lesions, patients with more extensive target lesion calcification were more likely to be older, have renal insufficiency, lower LVEF, and higher white blood cell count at baseline. They also more frequently received prior PCI.

In addition, moderately and severely calcified lesions were longer, more often total occlusions, bifurcations, and more likely to contain thrombi. Patients with moderate and severe target lesion calcification also had more extensive coronary disease, requiring a greater number of stents implanted. A similar proportion of DES were used in all groups.

Note: Dr. Stone and several study coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD

 

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Sources:
1. Généreux P, Madhavan MV, Mintz GA, et al. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI and ACUITY trials. J Am Coll Cardiol. 2014;Epub ahead of print.

2. Waters DD, Azar RR. The curse of target lesion calcification: still active after all these years [editorial]. J Am Coll Cardiol. 2014;Epub ahead of print.

 

 

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