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Gender-Based Differences in Outcomes After Orbital Atherectomy for the Treatment of De Novo Severely Calcified Coronary Lesions
Abstract: Objectives. We evaluated the relationship between gender and angiographic and clinical outcomes in patients with severely calcified lesions who underwent orbital atherectomy. Background. Female gender is associated with increased risk of adverse clinical events after percutaneous coronary intervention (PCI). Severe coronary artery calcification increases the complexity of PCI and increases the risk of adverse cardiac events. Orbital atherectomy is effective in plaque modification, which facilitates stent delivery and expansion. Whether gender differences exist after orbital atherectomy is unclear. Methods. Our analysis retrospectively analyzed 458 consecutive real-world patients (314 males and 144 females) from three centers who underwent orbital atherectomy. The primary endpoint was the major adverse cardiac and cerebrovascular event (MACCE) rate, defined as the composite of death, myocardial infarction (MI), target-vessel revascularization (TVR), and stroke, at 30 days. Results. The primary endpoint of MACCE was low and similar in females and males (0.7% vs 2.9%; P=.14). The individual endpoints of death (0.7% vs 1.6%; P=.43), MI (0.7% vs 1.3%; P=.58), TVR (0% vs 0%; P>.99), and stroke (0% vs 0.3%; P=.50) were low in both groups and did not differ. Angiographic complications were low: perforation (0.8% vs 0.7%; P>.90), dissection (0.8% vs 1.1%; P=.80), and no-reflow (0.8% vs 0.7%; P>.90). Conclusion. Plaque modification with orbital atherectomy was safe and provided similar angiographic and clinical outcomes between females and males. Randomized trials with longer-term follow-up are needed to support our results.
J INVASIVE CARDIOL 2016;28(11):440-443
Key words: atherectomy, calcification, percutaneous coronary intervention, coronary artery disease
Cardiovascular disease is the most common cause of death in females. Females may have atypical symptoms and are underdiagnosed compared with males. Females are older and have worse outcomes after percutaneous coronary intervention (PCI), including higher rates of death, stroke, repeat revascularization, and vascular complications.1-3
The presence of severe coronary artery calcium increases the complexity of PCI due to difficulty delivering the stent to the heavily calcified lesion as well as with optimal stent expansion. Repeated balloon angioplasty to dilate the resistant lesion can lead to periprocedural complications including myocardial ischemia and coronary dissection. The polymer of the drug-eluting stent can be damaged during stent delivery, which may increase neointimal hyperplasia and the risk of in-stent restenosis. The risk of death, myocardial infarction (MI), target-vessel revascularization (TVR), and stent thrombosis is higher with PCI of heavily calcified lesions.4
Orbital atherectomy is a safe and effective treatment strategy for patients with severely calcified coronary lesions prior to stent implantation.5 The outcomes of females who underwent orbital atherectomy in real-world practice are unknown. We assessed gender-based outcomes in patients with severely calcified lesions who underwent orbital atherectomy.
Methods
Study population. This retrospective multicenter analysis included 458 consecutive real-world patients with heavily calcified coronary lesions who underwent orbital atherectomy between October 2013 and December 2015 at three centers (St. Francis Hospital, Roslyn, New York; Northwell Health, Manhasset, New York; and UCLA Medical Center, Los Angeles, California). Heavily calcified lesions were defined by the presence of radiopacities on fluoroscopy involving the vessel wall. The institutional review board at the three institutions approved the review of the data.
Device description. The coronary orbital atherectomy system (Cardiovascular Systems, Inc) includes an eccentrically mounted crown that rotates at low speed (80,000 rpm) and high speed (120,000 rpm) over a 0.014˝ guidewire (ViperWire). The centrifugal force generated by the rotating eccentrically mounted crown differentially sands away hard calcified plaque, producing microembolic debris while improving vessel compliance for balloon predilation and stenting.
Procedure and medical treatment. Standard PCI techniques were used. Orbital atherectomy was initially performed with low speed (80,000 rpm), and with subsequent high-speed (120,000 rpm) atherectomy only if the vessel was at least 3 mm in diameter. The recommended duration of each pass was 20 seconds or less. Predilation angioplasty, choice of stent, antithrombotic regimen, and the use of left ventricular support device and intravascular imaging (intravascular ultrasound or optical coherence tomography) were all dictated by operator discretion. Dual-antiplatelet therapy was continued for a minimum of 1 month after bare-metal stenting and 12 months after drug-eluting stenting. Optimal medical therapy, including beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers, and statins were prescribed unless contraindicated.
Study endpoints. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), which was defined as the composite of death, myocardial infarction, target-vessel revascularization, and stroke at 30 days. Myocardial infarction was defined as recurrent symptoms with new ST-segment elevation or reelevation of cardiac markers to at least twice the upper limit of normal. Target-vessel revascularization was defined as percutaneous or surgical revascularization of the target lesion due to restenosis within the stent or in the 5 mm distal or proximal segments. Stent thrombosis was defined according to the Academic Research Consortium.6 Data were collected from medical records and entered into a PCI database.
Statistical analysis. Data are presented as mean ± standard deviation for continuous variables and frequency tables or proportions for discrete variables. Depending on the number of cases, paired samples t-test or Wilcoxon rank-sum test for continuous parameters and Chi-square or Fisher’s exact test for categorical parameters were used to compare the two groups. A multivariable Cox proportional hazard model was created with the use of baseline clinical and angiographic characteristics and procedure-related variables in order to identify independent predictors of MACCE. Statistical analyses were performed using SPSS 21.0 (IBM Corporation).
Results
Patient characteristics. Of the 458 patients who underwent orbital atherectomy, a total of 144 were female (31.4%) (Table 1). Female patients were older (75.4 ± 9.6 years vs 73.0 ± 10.0 years; P<.01) and had a higher prevalence of hypertension (93.1% vs 83.4%; P<.01) and hypercholesterolemia (85.4% vs 77.0%; P=.04).
Baseline angiographic and procedural characteristics. High-speed atherectomy was used less frequently in females (17.0% vs 27.6%; P=.04) (Table 2). Females had a smaller stent diameter (3.0 ± 0.5 mm vs 3.2 ± 0.5 mm; P=.03) and shorter total stent length (42.1 ± 25.7 mm vs 44.9 ± 26.6 mm; P<.01). Females required a lower amount of contrast (162.5 ± 72.4 mL vs 199.2 ± 97.3 mL; P<.01) and fluoroscopy time (18.9 ± 9.8 min vs 23.2 ± 20.2 min; P<.01).
Clinical outcomes. The primary endpoint of MACCE was low and similar in females and males (0.7% vs 2.9%; P=.14) (Table 3). The individual endpoints of death (0.7% vs 1.6%; P=.43), myocardial infarction (0.7% vs 1.3%; P=.58), target-vessel revascularization (0% vs 0%; P>.99), and stroke (0.0% vs 0.3%; P=.50) were low in both groups and did not differ. Angiographic complications were low and similar in female and male patients: perforation (0.8% vs 0.7%; P>.90), dissection (0.8% vs 1.1%; P=.80), and no-reflow (0.8% vs 0.7%; P>.90) (Table 4).
Of the 3 patients who had coronary perforation, 2 died. A 93-year-old female with an ejection fraction of 23% died from cardiac tamponade despite undergoing emergent pericardiocentesis and treatment with a covered stent. A 47-year-old male with cardiogenic shock on extracorporeal membrane oxygenation and multiple inotropes and severe unprotected left main, left anterior descending, and left circumflex arteries died from multiorgan failure despite treatment with a covered stent and subxiphoid window. The only patient who survived coronary perforation was an 81-year-old male who was treated with emergent pericardiocentesis, cardiopulmonary resuscitation, and insertion of an intraaortic balloon pump.
Predictors of MACCE. The following variables were entered into a stepwise multivariable Cox proportional hazard model for MACCE-free survival: age, diabetes, hypertension, kidney disease, previous coronary artery bypass surgery, and ejection fraction ≤40%. In the final Cox model, the only significant predictor of the hazard of MACCE was left ventricular ejection fraction ≤40% (hazard ratio, 9.4; 95% confidence interval, 2.4-36.8; P<.001) (Table 5).
Discussion
In the first and only study to assess gender-based differences in real-world patients with severely calcified lesions, females who underwent orbital atherectomy had low MACCE rates that were similar to males, despite more unfavorable baseline characteristics.
The ORBIT II trial demonstrated that orbital atherectomy of severely calcified coronary arteries facilitated stent delivery and decreased the incidence of adverse ischemic events compared with controls.5 As with most PCI studies, the majority of patients in the trial were male. Therefore, investigating the outcomes of females who underwent orbital atherectomy is needed to ensure that they derive similar clinical benefits from this technology compared with males (65%).
Studies assessing gender differences after PCI have reported mixed results. Several studies have demonstrated a higher risk of complications in females undergoing PCI.7,8 The increased safety risk may be attributed to worse premorbid factors, smaller coronary diameters, and delayed presentations of acute coronary syndromes in women. Furthermore, females have increased risk for access site and bleeding complications.1,8-10 However, in the drug-eluting stent era, data show similar outcomes in terms of safety and efficacy in women and men.11
Severe coronary artery calcification is associated with increased risk of adverse events after PCI.4 Data examining gender differences in heavily calcified vessels are limited. Studies evaluating gender-based differences after PCI with drug-eluting stents have generally excluded patients with heavily calcified vessels.12-14 Modification of severely calcified plaque with an atherectomy device may decrease procedure-related complications and increase procedural success. Rotational atherectomy is commonly used to modify calcified lesions prior to PCI.15 Female gender was an independent predictor of binary restenosis at 6-9 months after rotational atherectomy, followed by stenting moderately to severely calcified lesions.16
The only analysis of gender-based differences in patients with severely calcified coronary artery lesions who underwent orbital atherectomy was the analysis of the ORBIT II trial, which included 157 female patients.17 Females were older and had a lower estimated glomerular filtration rate, whereas males had a higher prevalence of prior coronary artery bypass graft surgery and were more likely to have a history of smoking. However, the rates of in-hospital and 30-day major adverse cardiovascular events were similar. Our results are consistent with the subanalysis of the ORBIT II trial.
When stratified by gender, the investigators reported no differences in major adverse cardiovascular event rates between the two groups. The rates of successful stent delivery and <50% restenosis were also similar. Although there were no differences in rates of coronary perforation, slow-flow/no-reflow, or abrupt closure, coronary dissection rates in women were significantly higher than males in the ORBIT II subanalysis, even after adjusting for baseline differences. The dissection rates of females and males in our analysis were similar.
High-speed atherectomy was used more frequently in males. This may be due to the larger reference vessel diameter as the mean stent diameter was larger in males compared with females. In general, low speed was used when the reference vessel diameter was <3 mm. High speed was used at the discretion of the operator if the reference vessel diameter was 3 mm, but routinely used if the diameter was ≥3.25 mm.
Study limitations. This study was retrospective, with a short duration of follow-up. Longer-term follow-up is needed to truly determine the presence of gender-based differences in clinical outcomes. Although the number of patients was small, this study included the largest number of patients who underwent orbital atherectomy. All consecutive patients, including those with myocardial infarction, cardiogenic shock, in extremis, and on hemodynamic support devices, were included in our analysis.
Conclusion
In the only analysis of gender differences in real-world patients, females with heavily calcified coronary lesions treated with orbital atherectomy had similar clinical and angiographic outcomes compared with males. A large prospective randomized trial with long-term follow-up is needed to truly determine the impact of gender on clinical and angiographic outcomes in patients who undergo orbital atherectomy.
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From the 1UCLA Medical Center, Los Angeles, California; 2Northwell Health, Manhasset, New York; and -3St. Francis Hospital — The Heart Center, Roslyn, New York.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee reports speaker’s bureau fees from Cardiovascular Systems, Inc. Dr E. Shlofmitz reports an institutional research grant and personal fees from Cardiovascular Systems, Inc. Dr Richard Shlofmitz reports personal fees from Cardiovascular Systems, Inc. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted April 18, 2016, provisional acceptance given May 13, 2016, final version accepted June 14, 2016.
Address for correspondence: Michael S. Lee, MD, 100 Medical Plaza, Suite 630, Los Angeles, CA 90095. Email: mslee@mednet.ucla.edu
