A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. RESULTS: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. CONCLUSIONS: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

An analysis of long-term clinical outcome following the use of excimer laser coronary atherectomy in a large UK PCI center.

BACKGROUND: Excimer laser atherectomy (ELCA) is an established adjunctive technique to facilitate acute success in percutaneous coronary intervention (PCI). Despite this there are a lack of contemporary outcome data, particulary longer-term, forpatients treated with ELCA PCI. AIMS: To evaluate the contemporary use ofELCA in PCI, the frequency of periprocedural complications and the longer-term outcomes associated with ELCA PCI. METHODS: This was a retrospective study that included all patients undergoing PCI (with or without ELCA) between April 2005 and May 2021. Relevant features from all cases were downloaded from the patient record and matched to hospital data on mortality on November 22, 2022. Kaplan Meier curves were used to compare mortality between the ELCA PCI and non-ELCA PCI cohorts with a landmark at 1 year. Multivariable Cox regression was performed to assess whether ELCA PCI was independently associated with long-term mortality. RESULT: There were 21,256 patients in this analysis, of which 448 (2.1%) were treated with ELCA PCI. ELCA PCI was associated with a higher frequency of any periprocedural complication. Median follow-up was 2812 days (IQR, 1577-4245 days) with higher mortality in ELCA PCI (38.2% vs. 29.0%, p < 0.001). However, on multivariable analysis, ELCA PCI was not independently associated with long-term mortality. The TVR frequency in ELCA PCI was 16.7% but TVR was significantly higher for cases of in-stent restenosis (ISR) (29.5%). CONCLUSION: Despite ELCA PCI being used in higher risk populations with complex coronary artery disease there was no long-term increased mortality associated with the use of this device. ELCA PCI for ISR is highly effective and safe although TVR in this cohort remains high in long-term follow-up.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis.

AIM: To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). METHODS AND RESULTS: In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. CONCLUSION: In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Novel application of intravascular lithotripsy in stent under-expansion: A single-center experience.

INTRODUCTION: Stent under-expansion due to calcification is associated with a less durable result. The development of intravascular lithotripsy (IVL) has provided clinicians with a readily available, simple-to-use treatment option for coronary calcification, but the use of IVL within a previously stented segment is currently off-license. There are, however, developing data suggesting that the use of IVL can be an effective treatment option for patients with calcific stent under-expansion. METHOD: This was a single-center study of all patients treated with IVL for calcific stent under-expansion between January 2019 and June 2021. The impact of IVL on quantitative coronary angiography (QCA) stenosis and on the minimal stent area (MSA) derived from intracoronary imaging were recorded. The presence of periprocedural complications and adverse cardiovascular events was obtained from the clinical record during the study timeframe. RESULTS: Thirty-nine patients underwent IVL for calcific stent under-expansion during the study time frame with one patient treated with more than one lesion in the same session. In all lesions, there was an improvement in the QCA stenosis with 37 (92.5%) having a residual stenosis of ≤30%. The mean QCA stenosis pre-IVL was 68 ± 21% and following IVL the mean QCA was 18 ± 9% (p < 0.001). In all lesions, there was an improvement in the MSA, with 26 (92.9%) achieving an MSA of more than 4.5 mm2 . The mean MSA pre-IVL was 3.88 ± 1.51 mm2 and following IVL the mean MSA was 7.41 ± 2.34 mm2 (p < 0.001). There were no major procedural complications. Over a mean follow-up of 506 ± 277 days, one patient died from ventricular arrhythmia but there were no other major adverse cardiovascular events. CONCLUSION: This single-center study demonstrates that IVL is a safe and effective treatment for calcific stent under-expansion with good medium-term results.

Variation in practice and concordance with guideline criteria for length of stay after elective percutaneous coronary intervention.

BACKGROUND: Considerable variability remains as regards the appropriate and safe length of stay after elective PCI. We performed a survey of interventional cardiologists to identify current views on appropriate and safe length of stay after PCI. METHODS: We created an online survey using the commercially available SurveyMonkey application. This was sent to interventional cardiologists in the US, Canada and the UK with the assistance of the national interventional cardiology societies (SCAI, CAIC/CCS, BCIS/BCS) as well as being made available on the theheart.org website. RESULTS: 505 interventional cardiologists responded, of which 237 were practicing in the US. Of those from the US, 52% were not aware of any guidelines for length of stay and 48% reported that their unit did not have a standard practice for length of stay. Same-day discharge after PCI was practiced as routine by 14% of cardiologists in the US versus 32% of cardiologists from Canada (P = 0.003) and 57% (P < 0.0001) from the UK. Amongst respondents, there was significant variation between respondents and divergence from published SCAI guidelines regarding appropriate length of stay for patient specific and procedural related clinical factors. CONCLUSIONS: There is considerable variation in practice patterns regarding length of stay after PCI. Whilst most cardiologists practice overnight observation, a significant minority utilize same-day discharge. There is also lack of familiarity with published guidelines. This variation and knowledge gap confirms an urgent need for updated guidelines and a concerted effort to educate cardiologists on appropriate post-PCI length of stay. © 2017 Wiley Periodicals, Inc.

Radial artery pseudoaneurysms after transradial cardiac catheterisation.

BACKGROUND: Although uncommon, radial artery access site complications are likely to become more frequent with the increased adoption of transradial cardiac catheterisation. There is a lack of data regarding the incidence and clinical features of radial artery pseudoaneuryms. We aimed to describe the incidence, clinical features and management of radial artery pseudoaneurysms in a high-volume transradial cardiac catheterisation centre. PATIENTS AND METHODS: We performed a search of the Vancouver Island Health Authority medical imaging database from 1st Jan 2008 to April 2012 looking for all radial and femoral artery pseudoaneuryms occurring after cardiac catheterisation. Hospital charts were reviewed to determine patient and procedural characteristics as well as management and outcome. RESULTS: There were a total of 14,968 coronary procedures performed over the four year search period, of which 13,216 (88%) were trans-radial. The incidence of radial artery pseudoaneurysm after cardiac catheterisation was 0.08%, and did not differ between transradial diagnostic angiography and PCI (0.07% vs 0.08%; P = 0.90). In contrast, the incidence of femoral artery pseudoaneurysm was higher, at 1.4% (P < 0.0001). Patients with radial pseudoaneurysms were generally elderly, with a median age of 77 years, and there were no gender differences. Only one patient had received a glycoprotein IIb/IIIa inhibitor, whilst two received warfarin post-procedure. The majority of cases (80%) were treated with surgical repair. CONCLUSIONS: We have demonstrated that radial artery pseudoaneuryms are a rare but important complication of transradial cardiac catheterisation, with patients generally requiring surgical repair. Most patients were elderly, but surprisingly only a minority were anti-coagulated with warfarin.

Feasibility and Efficacy of Herculink Elite ((TM)) Biliary Stent Implantation in Large Coronary Arteries (≥ 5 mm) and Venous Conduits: An Observational Study.

BACKGROUND AND OBJECTIVES: Percutaneous coronary intervention (PCI) in patients with lesions of large calibre coronary arteries (≥ 5 mm) and saphenous venous grafts (≥ 5 mm) can be challenging. There are no separate guidelines available to treat these vessels with PCI. Standard coronary stents of 4 mm diameter are used to treat these lesions conventionally but carry the risk of under deployment, distortion of stent architecture and future stent thrombosis even if they are subsequently expanded beyond 5 mm. METHODS AND RESULTS: Biliary stents (Herculink Elite™) provide a better alternative to standard coronary stents in these patients. These stents are of larger diameter (5-7 mm) and can be safely delivered over a 6 French sheath. In our case series, we demonstrate the use of intravascular ultrasound examination to confirm that biliary stents provide improved stent strut apposition within the coronary artery associated with extremely low repeat revascularisation rates. CONCLUSION: Our paper highlights that PCI of lesions in patients with large calibre coronary arteries can successfully be achieved using biliary stents.

Acute aortic occlusion with sudden paraplegia secondary to Aspergillus niger embolism from Aspergillus niger aortitis.

Acute aortic occlusion caused by a saddle embolus is a rare vascular emergency. Associated sudden paraplegia secondary to spinal cord ischemia is even more uncommon. Aspergillus surgical site infection is typically linked to cardiac surgery but is exceptional. Here we present a case that combines all of these factors. A 67-year-old man presented with sudden paraplegia from acute aortic occlusion with a saddle embolus from Aspergillus niger aortitis 4 months after aortic valve replacement and aortoplasty. We believe this to be the second reported case of Aspergillus niger aortitis and the first presenting as aortic occlusion with paraplegia.

Rotablation in the Very Elderly - Safer than We Think?

BACKGROUND/PURPOSE: Calcified coronary artery stenosis remains a challenge for Percutaneous Coronary Intervention (PCI). Calcium modification is facilitated by rotablation and is used in 1-3% of cases. Data on rotablation in patients ≥80 years is limited and perceived to be high risk. We compared PCI with rotablation and outcomes between patients ≥80 years and those <80 years. METHODS/MATERIALS: Retrospective analysis was performed of consecutive patients who underwent rotablation and PCI from 3 United Kingdom (UK) PCI Centres (2014-2017). In-hospital outcomes (composite of stroke, myocardial infarction, death, emergency coronary artery bypass graft surgery, vascular damage, coronary perforation, advanced AV-block, bleeding and renal impairment) and 30 day mortality risk score was compared between groups. RESULTS: 213 patients were included. 33.3% (n = 71) were ≥80 years. Baseline and angiographic characteristics were similar in the two groups. Older patients were more likely to present with acute coronary syndrome (ACS) (≥80 years 53.5% vs. 33.8% in <80 years, p = 0.006) and had increased hospital stay (≥80 years 2.8 days (±6.0) vs. 1.3 days (±1.9) <80 years, p = 0.009). Majority of PCI were performed through radial access (≥80 years 91.5% vs. 88.0% <80 years, p = 0.43). In-hospital composite outcomes were similar between the groups (≥80 years 5.6% vs. 4.9% <80 years, p = 1.0). The 30-day mortality risk score demonstrated a higher average risk of 2.5% in ≥80 years versus under 1% risk in <80 years (p < 0.001). CONCLUSION: This study demonstrates that outcomes after rotablation in the very elderly are similar to younger patients despite being high risk and presenting with ACS.

Contemporary Management of Stent Failure: Part One.

The occurrence of in-stent restenosis (ISR) still remains a daunting challenge in the current era, despite advancements in coronary intervention technology. The authors explore the underlying pathophysiology and mechanisms behind ISR, and describe how the use of different diagnostic tools helps to best elucidate these. They propose a simplistic algorithm to manage ISR, including a focus on how treatment strategies should be selected and a description of the contemporary technologies available. This article aims to provide a comprehensive outline of ISR that can be translated into evidence-based routine clinical practice, with the aim of providing the best outcomes for patients.

Flow cytometric analysis of circulating platelet-monocyte aggregates in whole blood: methodological considerations.

Platelet-monocyte aggregates are increasingly being used to quantify platelet activation. The variables that influence platelet-monocyte aggregates have not been well defined. We sought to determine the effect of blood collection, handling and processing techniques on detected levels of platelet-monocyte aggregates using a flow cytometric assay. Whole blood was labelled with anti-CD14-PE and anti-CD42a-FITC. Thereafter, samples were fixed and red cells lysed. Analysis was performed with the flow cytometer initially triggering on light scatter and then on FL-2 to identify CD14-PE positive monocytes. Platelet-monocyte aggregates were defined as monocytes positive for CD42a. The effect of collection, handling and processing techniques on this assay were assessed. Anticoagulation with heparin (20.1 +/- 2.0%), PPACK (16.8 +/- 1.9%), sodium citrate (12.3 +/- 1.6%) and EDTA (9.5 +/- 1.0%) resulted in markedly different levels of platelet-monocyte aggregation (P < 0.0001). Platelet-monocyte aggregation was higher in samples obtained from intravenous cannulae compared to those obtained by venepuncture (20.9 +/- 3.9% vs.13.8 +/- 2.4%, P = 0.03). For every 10 minutes of delay prior to processing platelet-monocyte aggregates increased by 2.8% (P = 0.0001) in PPACK anticoagulated blood and 1.7% (P = 0.01) in citrate anticoagulated blood. Erythrocyte lysis together with fixation does not affect platelet-monocyte aggregation. Platelet-monocyte aggregates remained stable over 24 hours when fixed and stored at 4 degrees C. Multiple handling and processing factors may affect platelet-monocyte aggregation. We recommend the measurement of platelet-monocyte aggregates on samples collected by direct venepuncture, using a direct thrombin inhibitor as the anticoagulant and minimising the time delay before sample fixation.

Coronary Intervention with the Excimer Laser: Review of the Technology and Outcome Data.

Excimer laser coronary atherectomy (ELCA) is a long-established adjunctive therapy that can be applied during percutaneous coronary intervention (PCI). Technical aspects have evolved and there is an established safety and efficacy record across a number of clinical indications in contemporary interventional practice where complex lesions are routinely encountered. The role of ELCA during PCI for thrombus, non-crossable or non-expandable lesions, chronic occlusions and stent under-expansion are discussed in this review. The key advantage of ELCA over alternative atherectomy interventions is delivery on a standard 0.014-inch guidewire. Additionally, the technique can be mastered by any operator after a short period of training. The major limitation is presence of heavy calcification although when rotational atherectomy (RA) is required but cannot be applied due to inability to deliver the dedicated RotaWireTM (Boston Scientific), ELCA can create an upstream channel to permit RotaWire passage and complete the case with RA - the RASER technique.

Late stent collapse identified with OCT - An underdiagnosed mechanism of restenosis?

Very late stent recoil is a rare albeit recognized phenomenon leading to subsequent in-stent restenosis. Angiography alone may not be adequate in making the diagnosis, and intravascular imaging with optical coherence tomography (OCT) is far superior in confirming the diagnosis and guiding subsequent management. We describe a case with interesting coronary angiogram and OCT images demonstrating very rare diagnosis of the late stent collapse. These images provide a valuable insight into a novel mechanism responsible for late target lesion failure. These images highlight the importance of modern intra-coronary imaging techniques in understanding the mechanisms underlying target-lesion failure, and guiding appropriate management.

Prolonged Clopidogrel Use is Associated with Improved Clinical Outcomes Following Drug-Eluting But Not Bare Metal Stent Implantation.

BACKGROUND: Guidelines recommend clopidogrel use for 6-12 months following drug-eluting stent (DES) implantation and 1-12 months following bare metal stent (BMS) implantation. The role of clopidogrel beyond 12 months is unclear. METHODS: We linked hospital administrative, community pharmacy and cardiac revascularization data to determine clopidogrel use and outcomes for all patients (those with acute presentations and those with stable angina) receiving a coronary stent in British Columbia 2004-2006, with follow-up until the end of 2008. Cox proportional hazard regression was performed to evaluate the effect of clopidogrel duration (≤12 vs. >12 months) on outcomes following BMS or DES implantation. Patients who died ≤12 months from index stent placement were excluded. RESULTS: A total of 15,629 patients were included in the study. Of 3599 patients who received at least one DES and 12,030 patients who received only BMS, 1326 (37 %) and 2121 (18 %), respectively, filled a prescription for clopidogrel >12 months from the index procedure. The mean duration of clopidogrel was 406 ± 35 days and 407 ± 37 days in the prolonged use (>12 months) DES and BMS cohorts, respectively, compared with 224 ± 112 days (p < 0.001) and 122 ± 117 days (p < 0.001), respectively, for patients receiving clopidogrel ≤12 months. Clopidogrel use beyond 12 months was associated with a reduction in mortality [hazard ratio (HR) 0.66, 95 % confidence interval (CI) 0.45-0.97] and the composite of mortality and readmission for myocardial infarction (HR 0.72, 95 % CI 0.55-0.94) in patients treated with DES, but not BMS alone. Prolonged clopidogrel use was not associated with bleeding-related mortality. CONCLUSIONS: Clopidogrel use beyond 12 months was associated with a reduction in death and hospitalization for myocardial infarction following DES, but not BMS, implantation. Our findings support a longer duration of clopidogrel therapy for patients treated with DES.

Prognostic Significance of Polymer Coatings in Zotarolimus-Eluting Stents.

Polymer coatings on drug-eluting stents (DES) serve as a vehicle for delivery of antirestenotic drugs. Whether they influence outcomes for contemporary DES is unknown. The evolution of polymer coatings for zotarolimus-eluting stents (ZES) provides a natural experiment that facilitates such analysis. The Resolute ZES (R-ZES) uses the same antirestenotic drug as the Endeavor ZES (E-ZES) but has a more biocompatible polymer with enhanced drug release kinetics. However, there are limited data on the real-world comparative efficacy of R-ZES and the preceding E-ZES. Thus, we analyzed 17,643 patients who received either E-ZES or R-ZES from 2008 to 2014 from the British Columbia Cardiac Registry. A total of 9,869 patients (56%) received E-ZES and 7,774 patients (44%) received R-ZES. Compared with E-ZES, R-ZES was associated with lower 2-year mortality (4.1% vs 6.4%, p <0.001) and 2-year target vessel revascularization (TVR; 6.8% vs 10.7%, p <0.001). R-ZES use was an independent predictor of lower mortality rate and TVR. This was confirmed in propensity-matched analyses for 2-year mortality (hazard ratio [HR] 0.59, 95% CI 0.49 to 0.71, p <0.001) and 2-year TVR (HR 0.86, 95% CI 0.75 to 0.98, p = 0.032). Instrumental variable analyses demonstrated R-ZES to be associated with lower 2-year mortality (Δ = -2.2%, 95% CI -4.3% to -0.2%, p = 0.032) and 2-year TVR (Δ = -3.3% to 95% CI -6.1% to -0.7%, p = 0.015). Acknowledging the limitations of observational analyses, this study has shown that R-ZES was associated with lower long-term TVR and mortality. These data are reassuring for the newer R-ZES and demonstrate how polymer coatings may influence the clinical performance of DES with wider implications for future DES development and design.

AXXESS™ Stent: Delivery Indications and Outcomes.

The successful treatment of coronary bifurcation lesions remains one of the challenges of interventional cardiology. The current consensus of the European Bifurcation Club based on published data advocates a provisional strategy, treating the main vessel (MV) with a single stent covering the side branch (SB), with bailout SB stenting as required. The success of this approach may be limited by failure to attain SB access after MV stenting but is preferred in most situations over routine SB plus MV stent techniques, which are associated with a significant increase in the rate of major adverse cardiac events. The AXXESS self-expanding biolimus-eluting stent has been developed as a solution to these challenges within the coronary circulation and maintains provisional MV stent approach but with added assurance of maintained SB access. It has a unique conical structure that is positioned spanning the carina, with scaffold extending into the carina of both the MV and SB. The purpose of this article is to describe the indication, implantation technique and outcome data supporting the use of the AXXESS stent in the treatment of coronary bifurcation lesions.

Delay in filling first clopidogrel prescription after coronary stenting is associated with an increased risk of death and myocardial infarction.

BACKGROUND: Patients frequently experience difficulties with medication compliance after hospital discharge. We investigated the effect of a delay in filling a first clopidogrel prescription after hospital discharge on clinical outcomes subsequent to coronary stenting. METHODS AND RESULTS: Hospital administrative, community pharmacy, and cardiac revascularization data were determined for all patients receiving a coronary stent in British Columbia 2004-2006 with follow-up out to 2 years. Cox's proportional hazard regression analysis, adjusting for baseline demographics and procedural variables, was performed to examine the effects of delay in filling a clopidogrel prescription after hospital discharge on clinical outcomes.Of 15 629 patients treated with coronary stents, 3599 received at least 1 drug-eluting stent (DES), whereas 12 030 received bare metal stents (BMS) alone. In total, 1064 (30%) and 3758 (31%) patients in the DES and BMS groups, respectively, failed to fill a prescription within 3 days of discharge (median, 1 day; interquartile range [IQR], 1 to 3). After regression analysis, a delay of >3 days was predictive of mortality and recurrent myocardial infarction (MI) irrespective of stent type (DES: hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.7 to 3.4; and HR, 2.0; 95% CI, 1.5 to 2.7, respectively, and BMS: HR, 2.2; 95% CI, 1.9 to 2.6; and HR, 1.8; 95% CI, 1.5 to 2.1, respectively). This excess hazard was greatest in the 30-day period immediately after hospital discharge (mortality: HR, 5.5; 95% CI, 3.5 to 8.6; and MI: HR, 3.1; 95% CI, 2.4 to 4.0, for all patients). CONCLUSIONS: Delays in patients filling their first prescription for clopidogrel after coronary stenting are common and associated with adverse clinical outcomes, irrespective of stent type. Strategies to reduce delays have the potential to improve clinical outcomes.

Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in male cigarette smokers.

OBJECTIVE: The effects of ω-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in healthy cigarette smokers; a group at increased risk of myocardial infarction. DESIGN, SETTING, PARTICIPANTS: Twenty cigarette smokers were recruited into a randomised, double-blind, placebo-controlled, crossover trial of ω-3 fatty acid supplementation. INTERVENTION: ω-3 fatty acid supplements (2 g/day) or placebo for a 6-week period. MAIN OUTCOME MEASURES: Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 smokers during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion. RESULTS: All vasodilators caused dose-dependent increases in FBF (p<0.0001). Compared with placebo, ω-3 fatty acid supplementation led to greater endothelium-dependent vasodilatation with acetylcholine and substance P (p=0.0032 and p=0.056). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001) that was greater after ω-3 fatty acid supplementation compared with placebo (8.8±2.3 IU ml(-1) vs 3.6±1.1 IU ml(-1); p=0.029). ω-3 fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40. CONCLUSIONS: We have demonstrated for the first time that ω-3 fatty acids augment acute endothelial t-PA release and improve endothelial vasomotor function in cigarette smokers. Improved endogenous fibrinolysis and endothelial function may represent important mechanisms through which ω-3 fatty acids confer potential cardiovascular benefits.