Multi-vessel stenting during primary percutaneous coronary intervention for acute myocardial infarction. A single-center experience

BACKGROUND: Recanalization of the culprit lesion is the main goal of primary angioplasty for acute ST-segment elevation myocardial infarction (STEMI). Patients presenting with acute myocardial infarction and multivessel disease are, therefore, usually subjected to staged procedures, with the primary percutaneous coronary intervention (PCI) confined to recanalization of the infarct-related artery (IRA). Theoretically at least, early relief of stenoses of non-infarct-related arteries could promote collateral circulation, which could help to limit the infarct size. However, the safety and feasibility of such an approach has not been adequately established. METHODS: In this single-center prospective study we examined 73 consecutive patients who had an acute STEMI and at least one or more lesions > or = 70% in a major epicardial vessel other than the infarct-related artery. In the first 28 patients, forming the multi-vessel (MV) PCI group, all lesions were treated during the primary procedure. In the following 45 patients, forming the culprit-only (CO) PCI group, only the culprit lesion was treated during the initial procedure, followed by either planned-staged or ischemia-driven revascularization of the non-culprit lesions. Fluoroscopy time and contrast dye amount were compared between both groups, and patients were followed up for one year for major adverse cardiac events (MACE) and other significant clinical events. RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the MV-PCI group, 2.51 lesions per patient were treated using 2.96 +/- 1.34 stents (1.00 lesions and 1.76 +/- 1.17 stents in the CO-PCI group, both p < 0.001). The fluoroscopy time increased from 10.3 (7.2-16.9) min in the CO-PCI group to 12.5 (8.5-19.3) min in the MV-PCI group (p = 0.22), and the amount of contrast used from 200 (180-250) ml to 250 (200-300) ml, respectively (p = 0.16). Peak CK and CK-MB were significantly lower in patients of the MV-PCI group (843 +/- 845 and 135 +/- 125 vs 1652 +/- 1550 and 207 +/- 155 U/l, p < 0.001 and 0.01, respectively). Similar rates of major adverse cardiac events at one year were observed in the two groups (24% and 28% in multi-vessel and culprit treatment groups, p = 0.73). The incidence of new revascularization in both infarct- and non-infarct-related arteries was also similar (24% and 28%, respectively, p = 0.73). CONCLUSION: We may state from this limited experience that a multi-vessel stenting approach for patients with acute STEMI and multi-vessel disease is feasible and probably safe during routine clinical practice. Our data suggest that this approach may help to limit the infarct size. However, larger studies, perhaps using drug-eluting stents, are still needed to further evaluate the safety and efficiency of this procedure, and whether it is associated with a lower need of subsequent revascularization and lower costs.

[The role of percutaneus coronary interventions in the treatment of coronary artery disease]

In industrial countries, cardiovascular diseases remain the primary cause of death. This review summarizes the role of percutaneous coronary interventions (PCI) in the treatment of coronary heart disease. Interventional therapy of coronary artery disease was initiated in 1977 with the introduction of balloon angioplasty by Andreas Grüntzig in Zurich. Technical progress since has been related to construction and materials of catheters, but also to digital processing of x-ray imaging. Additional methods - rotablation, atherectomy, laser, intravascular ultrasound, and most importantly stent implantation were developed. Only stents significantly changed the procedure. They are today an integral part of PCI.

Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol

BACKGROUND The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.

Restenosis after infrapopliteal angioplasty - clinical importance, study update and further directions.

Patients with critical limb ischemia (CLI) represent the most severe form of peripheral arterial disease (PAD) and exhibit high mortality rates. Frequently, PAD in CLI patients involves the infrapopliteal arterial segment challenging endovascular revascularization strategies. Restenosis remains the major drawback of tibial angioplasty encountered in more than two thirds of CLI patients undergoing tibial revascularization. In contrast to earlier observations, tibial patency was recently shown to be essential to attain an optimal clinical outcome in CLI patients subsequent to tibial angioplasty. The exact pathopyhsiological mechanisms of tibial restenosis remains unclear. To date, most of our knowledge on tibial restenosis and its pathophysiology is derived from coronary arteries, based on the similarity of coronary arteries to tibial artery morphology. Nervertheless, multiple antirestenosis concepts are investigated within clinical trials to reduce tibial restenosis.Purpose of the present manuscript is to provide a current update on the pathophysiology of tibial restenosis and potential antirestenosis strategies.

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

OBJECTIVE To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE All cause mortality. RESULTS 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

Functional assessment of collaterals in the human coronary circulation.

The coronary collateral circulation is an alternative source of blood supply to a myocardial area jeopardized by the failure of the stenotic or occluded vessel to provide enough blood flow to this region. Until recently, only qualitative or semiqualitative methods have been available for the assessment of the coronary collateral circulation in humans, such as the patient's history of walk-through angina pectoris, the registration of intracoronary ECG signs for myocardial ischaemia or angina pectoris during coronary occlusion, or coronary angiographic classification (score 0-3) of collaterals. Studies of coronary wedge pressure measurements distal of a balloon-occluded coronary artery and the recent advent of ultrathin pressure and Doppler angioplasty guidewires have made it possible to obtain pressure or flow velocity data in remote vascular areas and, thus, to calculate functional variables for coronary collateral flow. Those coronary occlusive pressure- and flow velocity-derived parameters express collateral flow as a fraction of antegrade coronary flow during vessel patency of the collateral-receiving vessel. They are both interchangeable, and they have been validated in comparison to 'traditional' methods and against each other. The possibility of accurately measuring coronary collateral flow indices in humans undergoing coronary balloon angioplasty opens areas of investigation of the pathogenesis, pathophysiology and therapeutic promotion of the collateral circulation previously reserved for exclusively experimental studies. The purpose of this article is to review several clinically available methods for the functional characterization of the coronary collateral circulation.

Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a network meta-analysis.

BACKGROUND Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR. METHODS We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191. FINDINGS We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6-12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of -9·0% (95% CI -15·8 to -2·2) versus drug-coated balloons (DCB), -9·4% (-17·4 to -1·4) versus sirolimus-eluting stents, -10·2% (-18·4 to -2·0) versus paclitaxel-eluting stents, -19·2% (-28·2 to -10·4) versus vascular brachytherapy, -23·4% (-36·2 to -10·8) versus bare metal stents, -24·2% (-32·2 to -16·4) versus balloon angioplasty, and -31·8% (-44·8 to -18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (-0·2% [95% CI -6·2 to 5·6]) or paclitaxel-eluting (-1·2% [-6·4 to 4·2]) stents. INTERPRETATION These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer. FUNDING None.

A double-blind randomised study to evaluate the efficacy and safety of bindarit in preventing coronary stent restenosis.

AIMS Bindarit (BND) is a selective inhibitor of monocyte chemotactic protein-1 (MCP-1/CCL2), which plays an important role in generating intimal hyperplasia. Our aim was to explore the efficacy and safety of bindarit in preventing restenosis following percutaneous coronary intervention. METHODS AND RESULTS A phase II, double-blind, multicentre randomised trial included 148 patients randomised into three arms (BND 600 mg, n=48; BND 1,200 mg, n=49; PLB, n=51). Bindarit was given following PCI and continued for 180 days. Monthly clinical follow-up and six-month coronary angiography were conducted. The primary endpoint was in-segment late loss; the main secondary endpoints were in-stent late loss and major adverse cardiovascular events. Efficacy analysis was carried out on two populations, ITT and PP. There were no significant differences in the baseline characteristics among the three treatment groups. In-segment and in-stent late loss at six months in BND 600, BND 1,200 and PLB were: (ITT 0.54 vs. 0.52 vs. 0.72; p=0.21), (PP 0.46 vs. 0.53 vs. 0.72; p=0.12) and (ITT 0.74 vs. 0.74 vs. 1.05; p=0.01), (PP 0.66 vs. 0.73 vs. 1.06; p=0.003), respectively. The MACE rates at nine months among treatment groups were 20.8% vs. 28.6% vs. 25.5% (p=0.54), respectively. CONCLUSIONS This was a negative study with the primary endpoint not being met. However, significant reduction in the in-stent late loss suggests that bindarit probably exerts a favourable action on the vessel wall following angioplasty. Bindarit was well tolerated with a compliance rate of over 90%. A larger study utilising a loading dose and targeting a specific patient cohort may demonstrate more significant results.

Upstream clopidogrel, prasugrel, or ticagrelor for patients treated with primary angioplasty: Results of an angiographic randomized pilot study.

OBJETIVES The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood. METHODS A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration. RESULTS Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022). CONCLUSIONS In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.

A cost-effectiveness analysis of fluvastatin in patients with diabetes after successful percutaneous coronary intervention

Background: The Lescol Intervention Prevention Study (LIPS) was a multinational randomized controlled trial that showed a 47% reduction in the relative risk of cardiac death and a 22% reduction in major adverse cardiac events (MACEs) from the routine use of fluvastatin, compared with controls, in patients undergoing percutaneous coronary intervention (PCI, defined as angioplasty with or without stents). In this study, MACEs included cardiac death, nonfatal myocardial infarction, and subsequent PCI and coronary artery bypass graft. Diabetes was the greatest risk factor for MACEs. Objective: This study estimated the cost-effectiveness of fluvastatin when used for secondary prevention of MACEs after PCI in people with diabetes. Methods: A post hoc subgroup analysis of patients with diabetes from the LIPS was used to estimate the effectiveness of fluvastatin in reducing myocardial infarction, revascularization, and cardiac death. A probabilistic Markov model was developed using United Kingdom resource and cost data to estimate the additional costs and quality-adjusted life-years (QALYs) gained over 10 years from the perspective of the British National Health Service. The model contained 6 health states, and the transition probabilities were derived from the LIPS data. Crossover from fluvastatin to other lipid-lowering drugs, withdrawal from fluvastatin, and the use of lipid-lowering drugs in the control group were included. Results: In the subgroup of 202 patients with diabetes in the LIPS trial, 18 (15.0%) of 120 fluvastatin patients and 21 (25.6%) of 82 control participants were insulin dependent (P = NS). Compared with the control group, patients treated with fluvastatin can expect to gain an additional mean (SD) of 0.196 (0.139) QALY per patient over 10 years (P < 0.001) and will cost the health service an additional mean (SD) of 10 (E448) (P = NS) (mean [SD] US $16 [$689]). The additional cost per QALY gained was;(51 (US $78). The key determinants of cost-effectiveness included the probabilities of repeat interventions, cardiac death, the cost of fluvastatin, and the time horizon used for the evaluation. Conclusion: Fluvastatin was an economically efficient treatment to prevent MACEs in these patients with diabetes undergoing PCI.

Asymptomatic long-term survivors of coronary artery bypass surgery enjoy a quality of life equal to the general population

Background Health-related quality of life (HRQOL) among long-term survivors of coronary artery bypass surgery is an important outcome that has been little studied at the population level. Methods A postal survey was conducted in 1999 to 2000 in patients 6 to 20 years after coronary artery bypass graft (CABG) surgery in Western-Australia. A random stratified sample of 2500 was drawn from 8910 patients who had their first CABG surgery in 1980 to 1993. Health-related quality of life was measured with Short Form 36 and EuroQol visual analogue scale. Results Response was 82% (n = 2061). Health-related quality of life declined with age and was similar for men and women, although scores for women were worse for physical functioning. Compared with Australian population norms, the age- and sex-standardized scores of survivors of CABG were generally worse, mainly in the physical domain. Reported angina at the time of follow-up (33%), symptoms of heart failure equivalent to New York Heart Association (NYHA) classes II to IV (34%), and comorbidities such as diabetes and hypertension were associated with poorer HRQOL. For both men and women without angina or heart failure at follow-up, HRQOL was no different from that of the general population. Conclusion Overall, the quality of life among long-term survivors of CABG is worse than that of the general population, the difference being mainly attributable to recurrent symptoms and comorbidities. Quality of life for those without angina or heart failure at follow-up was equivalent to the population norms, providing an incentive to maximize efforts to abolish angina and ameliorate heart failure symptoms.

Gender difference in the use of coronary interventions for patients with acute coronary syndrome: experience from a major metropolitan hospital in Melbourne, Australia

BACKGROUND: Literature suggests an ongoing gender disparity in the use of coronary angiography and subsequent interventions among patients with acute coronary syndrome (ACS). OBJECTIVES: The study aimed to examine gender differences in the use of coronary interventions amongst patients with acute coronary syndrome (ACS) admitted to a major metropolitan hospital in Melbourne during the period 2009-2012. METHODS: We undertook a retrospective analysis of a hospital database of 2096 ACS patients. ACS included unstable angina (UA), ST-segment-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). RESULTS: The mean age of the patients was 64.3 years and 624 (30%) were women. Half of them were diagnosed as NSTEMI, 23% as STEMI and 25% as UA. Compared to men, women were older at admission, less likely to be diagnosed with STEMI and less likely to smoke. No gender difference was observed for severe co-morbidities or use of coronary angiography. Women diagnosed with STEMI were 39% less likely to receive an angioplasty stent (adjusted odds ratio 0.61, 95% confidence intervals 0.39-0.96) and 66% less likely to receive grafts (adjusted OR 0.34, 95% CIs 0.13-0.93). Women diagnosed with NSTEMI were 44% less likely to receive grafts (adjusted OR 0.56, 95% CIs 0.37-0.83). Younger women aged 35-49 years were less likely to receive an angioplasty stent, and older women >50 years were less likely to receive grafts. CONCLUSIONS: Adherence to guideline based treatment will help to ensure knowledge translation from guideline to practice. Further research investigating symptom presentation, use of non-invasive tests and medical management of ACS by gender may further explain gender difference for coronary interventions.

Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Comprehensive standardized data definitions for acute coronary syndrome research in emergency departments in Australasia

Patients with chest discomfort or other symptoms suggestive of acute coronary syndrome (ACS) are one of the most common categories seen in many Emergency Departments (EDs). While the recognition of patients at high-risk of ACS has improved steadily, identifying the majority of chest pain presentations who fall into the low-risk group remains a challenge. Research in this area needs to be transparent, robust, applicable to all hospitals from large tertiary centres to rural and remote sites, and to allow direct comparison between different studies with minimum patient spectrum bias. A standardised approach to the research framework using a common language for data definitions must be adopted to achieve this. The aim was to create a common framework for a standardised data definitions set that would allow maximum value when extrapolating research findings both within Australasian ED practice, and across similar populations worldwide. Therefore a comprehensive data definitions set for the investigation of non-traumatic chest pain patients with possible ACS was developed, specifically for use in the ED setting. This standardised data definitions set will facilitate ‘knowledge translation’ by allowing extrapolation of useful findings into the real-life practice of emergency medicine.