Annapoorna Kini

Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease

BACKGROUND In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. METHODS In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). CONCLUSIONS In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study

BACKGROUND Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. METHODS The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. FINDINGS We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. INTERPRETATION In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. FUNDING Bristol-Myers Squibb and Sanofi-Aventis.

Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials

OBJECTIVES We evaluated the impact of the everolimus-eluting stent (EES) on the frequency of stent thrombosis (ST), target vessel revascularization (TVR), myocardial infarction (MI), and cardiac death in randomized controlled trials comparing the EES to non-everolimus-eluting drug-eluting stents (EE-DES). BACKGROUND Whether or not the unique properties of the EES translate into reductions in ST remains unknown. METHODS We searched MEDLINE, Scopus, the Cochrane Library, and Internet sources for articles comparing outcomes between EES and non-EE-DES without language or date restriction. Randomized controlled trials reporting the frequency of ST were included. Variables relating to patient and study characteristics and clinical endpoints were extracted. RESULTS We identified 13 randomized trials (n = 17,101) with a weighted mean follow-up of 21.7 months. Compared with non-EE-DES, the EES significantly reduced ST (relative risk [RR]: 0.55; 95% confidence interval [CI]: 0.38 to 0.78; p = 0.001), TVR (RR: 0.77; 95% CI: 0.64 to 0.92; p = 0.004), and MI (RR: 0.78; 95% CI: 0.64 to 0.96; p = 0.02). There was no difference in cardiac mortality between the groups (RR: 0.92; 95% CI: 0.74 to 1.16; p = 0.38). The treatment effect was consistent by different follow-up times and duration of clopidogrel use. The treatment effects increased with higher baseline risks of the respective control groups with the strongest correlation observed for ST (R(2) = 0.89, p < 0.001). CONCLUSIONS Intracoronary implantation of the EES is associated with highly significant reductions in ST with concordant reductions in TVR and MI compared to non-EE-DES. Whether these effects apply to different patient subgroups and DES types merits further investigation.

Creatine Kinase-MB Elevation After Coronary Intervention Correlates With Diffuse Atherosclerosis, and Low-to-Medium Level Elevation Has a Benign Clinical Course Implications for Early Discharge After Coronary Intervention

OBJECTIVES The study evaluated the incidence and predictors of creatine kinase-MB isoenzyme (CK-MB) elevation after successful coronary intervention using current devices, and assessed the influence on in-hospital course and midterm survival. BACKGROUND The CK-MB elevation after coronary intervention predominantly using balloon angioplasty correlates with late cardiac events of myocardial infarction (MI) and death. Whether CK-MB elevation after nonballoon devices is associated with an adverse short and midterm prognosis is unknown. METHODS The incidence and predictors of CK-MB elevation after coronary intervention were prospectively studied in 1,675 consecutive patients and were followed for in-hospital events and survival. RESULTS CK-MB elevation was detected in 313 patients (18.7%), with 1-3x in 12.8%, 3-5x in 3.5% and >5x normal in 2.4% of patients. Procedural complications or electrocardiogram changes occurred in only 49% of the CK-MB-elevation cases; CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after percutaneous transluminal coronary angioplasty; p < 0.01). Predictors of CK-MB elevation on multivariate analysis were diffuse coronary disease (p = 0.02), systemic atherosclerosis (p = 0.002), stent use (p = 0.04) and absence of beta-blocker therapy (p = 0.001). Adverse in-hospital cardiac events were more frequent in patients with >5x CK-MB elevation, with no significant difference between 1-5x CK-MB elevation versus normal CK-MB group. During a mean follow-up of 13 +/- 3 months, the incidence of death in the CK-MB-elevation group was 1.6% versus 1.3% in the normal CK-MB group (p = NS). CONCLUSIONS The CK-MB elevation after coronary intervention was observed even in the absence of discernible procedural complications and was more common in patients with diffuse atherosclerosis. In-hospital clinical events requiring prolonged monitoring were higher in >5x CK-MB-elevation patients only. Midterm survival of CK-MB-elevation patients was similar to those with normal CK-MB. Our prospective analysis shows a lack of adverse in-hospital cardiac events and suggests that early discharge of stable 1-5x normal CK-MB-elevation patients after successful coronary intervention is safe.

Refractory angina pectoris: mechanism and therapeutic options.

As the survival of patients with primary coronary events continues to increase, the number of patients presenting with coronary artery disease unsuitable to further revascularization techniques and symptoms refractory to medical therapy also continues to rise. The aims of this review were to define the population of patients with refractory angina pectoris and to present the therapeutic options currently available for this condition. Refractory angina pectoris is defined, and traditional medical therapies are discussed. Then, current therapeutic options for patients with refractory angina are extensively reviewed. A multitude of therapeutic options exist for patients with refractory angina pectoris. Small, uncontrolled studies have shown a potential benefit for additional antiplatelet and antithrombotic therapy. In randomized trials, neurostimulation has been shown to be effective in reducing angina symptoms. Enhanced external counterpulsation is a viable treatment option for select patients with refractory angina. In many randomized trials, laser revascularization has been shown to diminish angina symptoms, although no placebo-controlled studies exist to date. Gene therapy is a promising area of research in this field. Percutaneous in situ coronary venous arterialization is in its infancy, but may be able to treat many patients if proved successful. No data support the role of chelation therapy in this population. Heart transplantation remains a final option for these patients. Further research of the techniques mentioned in this review is warranted. The importance of randomized, double-blinded, placebo-controlled trials cannot be overemphasized, as the placebo effect of these therapies is probably marked.

Detection of Lipid-Core Plaques by Intracoronary Near-Infrared Spectroscopy Identifies High Risk of Periprocedural Myocardial Infarction

Background— Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. Methods and Results— The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI4 mm ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI4 mm ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI4 mm (P=0.0002). Conclusions— NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention.

Rotational atherectomy for in-stent restenosis: acute and long-term results of the first 100 cases

OBJECTIVES This study evaluated the clinical safety and long-term results of rotational atherectomy (RA) followed by low-pressure balloon dilatation (percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of in-stent restenosis (ISR). BACKGROUND In-stent restenosis is associated with a high incidence of recurrence after interventional treatment. Because ISR is due to neointimal hyperplasia, rotational ablation may be a more effective treatment than PTCA. METHODS Between November 1995 and November 1996, 100 consecutive patients with first-time ISR were treated by RA. Quantitative coronary angiography and intravascular ultrasound (IVUS) were used to analyze the acute procedural results. The incidence of repeat in-stent restenosis and target vessel revascularization (TVR) at follow-up was determined. RESULTS Procedural success without any major in-hospital complications was achieved in 100% of cases. Slow flow was observed in 3% and creatine kinase-MB enzyme elevation >3x normal occurred in 2%. The mean burr-to-artery ratio was 0.68+/-0.18 and adjuvant balloon dilatation was performed at 4.2+/-2.1 atm. Minimum luminal diameter increased from 0.86+/-0.28 mm to 1.89< or =0.21 mm after RA and to 2.56+/-0.29 mm after adjunct PTCA. Quantitative IVUS analysis showed that 77% of the luminal gain occurred due to rotational ablation of the restenotic tissue and only 23% occurred after adjunct balloon dilation, and further stent expansion did not contribute to the luminal enlarge. ment. At a mean follow-up of 13+/-5 months, repeat in-stent restenosis occurred in 28% of patients with TVR of 26%. Univariate predictors of repeat restenosis were burr-to-artery ratio <0.6, ISR in <90 days of stenting, ostial lesion, stent for a restenotic lesion and diffuse type ISR. CONCLUSIONS Rotational atherectomy is a safe and feasible technique for treatment of ISR and is associated with a relatively low recurrent restenosis in comparison to historical controls of balloon angioplasty.

Detection by Near-Infrared Spectroscopy of Large Lipid Core Plaques at Culprit Sites in Patients With Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI). BACKGROUND Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients. METHODS We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI(4mm)). RESULTS MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445 to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm) >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%). CONCLUSIONS The present study has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a signature of plaques causing STEMI.

Cardioprotective Effect of Prior β-Blocker Therapy in Reducing Creatine Kinase-MB Elevation After Coronary Intervention: Benefit Is Extended to Improvement in Intermediate-Term Survival

BACKGROUND Both retrospective studies and prospective randomized trials have shown that beta-blockers improve survival and reduce the risk of reinfarction in patients with myocardial infarction. To evaluate whether beta-blockers exert similar protective benefits during and after coronary intervention, we studied the incidence of postprocedure creatine kinase (CK)-MB elevation in patients with or without prior beta-blocker therapy and its effect on intermediate-term ( approximately 1 year) survival. METHODS AND RESULTS We prospectively analyzed 1675 consecutive patients undergoing coronary intervention; of these patients, 643 (38.4%) were on beta-blocker therapy before the intervention. The incidence of CK-MB elevation after coronary intervention was 13.2% in patients on beta-blocker therapy before intervention and 22.1% in patients who were not on beta-blockers (P<0.001). Patients with prior beta-blocker therapy had lower persistent/recurrent postprocedure chest pain and lower preprocedure and postprocedure heart rates and mean blood pressures compared with patients who were not on beta-blockers (P<0.001). Multiple linear regression analysis revealed prior beta-blocker therapy as the sole independent factor for lower CK-MB release after coronary intervention. During intermediate-term follow-up at 15+/-3 months, patients on beta-blocker therapy before intervention had lower mortality rates compared with those not on beta-blockers (0.78% versus 1.96%; P=0. 04), although the benefit was independent of the reduction in CK-MB release. CONCLUSIONS Our nonrandomized, prospective analysis suggests that prior beta-blocker therapy has a cardioprotective effect in limiting CK-MB release after coronary intervention and that it is associated with a lower mortality at intermediate-term follow-up.

Current status of rotational atherectomy.

Rotational atherectomy facilitates percutaneous coronary intervention for complex de novo lesions with severe calcification. A strategy of routine rotational atherectomy has not, however, conferred reduction in restenosis or major adverse cardiac events. As it is technically demanding, rotational atherectomy is also uncommon. At this 25-year anniversary since the introduction of rotational atherectomy, we sought to review the current state-of-the-art in rotational atherectomy technique, safety, and efficacy data in the modern era of drug-eluting stents, strategies to prevent and manage complications, including slow-flow/no-reflow and burr entrapment, and appropriate use in the context of the broader evolution in the management of stable ischemic heart disease. Fundamental elements of optimal technique include use of a single burr with burr-to-artery ratio of 0.5 to 0.6-rotational speed of 140,000 to 150,000 rpm, gradual burr advancement using a pecking motion, short ablation runs of 15 to 20 s, and avoidance of decelerations >5,000 rpm. Combined with meticulous technique, optimal antiplatelet therapy, vasodilators, flush solution, and provisional use of atropine, temporary pacing, vasopressors, and mechanical support may prevent slow-flow/no-reflow, which in contemporary series is reported in 0.0% to 2.6% of cases. On the basis of the results of recent large clinical trials, a subset of patients with complex coronary artery disease previously assigned to rotational atherectomy may be directed instead to medical therapy alone or bypass surgery. For patients with de novo severely calcified lesions for which rotational atherectomy remains appropriate, referral centers of excellence are required.