The role of the vascular surgeon in transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for severe aortic valve stenosis in patients at increased surgical risk. Percutaneous transfemoral (TF) is the access of choice due to its reduced invasiveness and perioperative morbidity/mortality compared with the trans-axillary, aortic, and apical routes. On the other hand, vascular access complications (VACs) of the TF access are associated with prolonged hospitalization, 30-day, and 1-year mortality. In addition, the concomitance of peripheral arterial disease may require associated endovascular management. A multidisciplinary team with Interventional Cardiologists and Vascular Surgeons may minimize the rate of VACs in patients with challenging femoral-iliac access or concomitant disease of other vascular districts, thus optimizing the outcome of TF-TAVI. The aim of this study was to evaluate the role of Vascular Surgeons in TF TAVI procedures. METHODS: We conducted a retrospective single-center review of all TF-TAVI procedures assisted by Vascular Surgeons between January 2016 and December 2020 in a high-volume tertiary hospital. Pre, intra, and postoperative data were analyzed by a dedicated group of Interventional Cardiologists and Vascular Surgeons. VACs were defined according with the Valve Academic Research Consortium (VARC) three guidelines. The outcomes of TF-TAVI procedures with Vascular Surgeons involvement were assessed as study's endpoints. RESULTS: Overall, 937 TAVI procedures were performed with a TF approach ranging between 78% (2016) and 98% (2020). Vascular Surgeons were involved in 67 (7%) procedures with the following indications: concomitant abdominal aortic aneurysm (EVAR + TAVI) - 3 (4%), carotid stenosis (TAVI + CAS) - 2 (3%), hostile femoral/iliac access, or VACs - 62 (93%). Balloon angioplasty of iliac artery pre-TAVI implantation was performed in 51 cases (conventional PTA: 38/51%-75%; conventional PTA + intravascular lithotripsy: 13/51%-25%; stenting: 5/51%-10%). TAVI procedure was successfully completed by percutaneous TF approach in all 62 cases with challenging femoral/iliac access. VACs necessitating interventions were 18/937 (2%) cases, localized to the common femoral or common/external iliac artery in 15/18 (83%) and 3/18 (17%) cases, respectively. They were managed by surgical or endovascular maneuvers in 3/18 (17%) and 15/18 (83%) cases, respectively. Fifteen/18 (83%) VACs were treated during the index procedure. There was no procedure-related mortality or 30-day readmission. CONCLUSION: In our experience, Vascular Surgeon assistance in TAVI procedures was not infrequent and allowed safe and effective device introduction through challenging TF access. Similarly, the concomitant significant disease of other vascular districts could be safely addressed, potentially reducing postoperative related mortality and morbidity. The implementation of multidisciplinary team with interventional cardiologists and vascular surgeons should be encouraged whenever possible.

A novel high-risk aortic root anatomy for right coronary artery occlusion during TAVI.

Acute coronary occlusion during transcatheter aortic valve implantation (TAVI) is a rare but potentially lethal complication. Main mechanisms are sinus insufficiency or sinus sequestration with well-described risk factors. We present two cases of acute right coronary artery occlusion during TAVI with a self-expanding valve in the absence of classical risk factors and propose a novel mechanism.

Predictors of bail-out stenting in patients with small vessel disease treated with drug-coated balloon percutaneous coronary intervention.

BACKGROUND: Drug-coated balloons (DCBs) have shown comparable results with drug-eluting stents in small vessel disease (SVD) percutaneous coronary intervention (PCI) in terms of target vessel revascularization and a reduced incidence of myocardial infarction. However, the relatively high rate of bail-out stenting (BOS) still represents a major drawback of DCB PCI. AIMS: The aim of the study was to investigate the clinical, anatomic, and procedural features predictive of BOS after DCB PCI in SVD. METHODS: We included all consecutive patients undergoing PCI at our institution between January 2020 and May 2022 who were treated with DCB PCI of a de novo lesion in a coronary vessel with a reference vessel diameter (RVD) between 2.0 and 2.5 mm. Angiographic success was defined as a residual stenosis <30% without flow-limiting dissection. Patients who did not meet these criteria underwent BOS. RESULTS: A total of 168 consecutive patients and 216 coronary stenoses were included. The rate of bail-out stent was 13.9%. On multivariate analysis, DCB/RVD ratio (odds ratio [OR]: 4.39, 95% confidence interval [CI]: 1.71-11.29, p < 0.01), vessel tortuosity (OR: 7.00, 95% CI: 1.66-29.62, p < 0.01), distal vessel disease (OR: 5.66, 95% CI: 2.02-15.83, p < 0.01), and high complexity (Grade C of ACC/AHA classification) coronary stenoses (OR: 6.31, 95% CI: 1.53-26.04, p = 0.01) were independent predictors of BOS. CONCLUSIONS: BOS is not an infrequent occurrence in DCB PCI of small vessels and is correlated with vessel tortuosity, distal diffuse vessel disease, higher lesion complexity, and balloon diameter oversizing.

Iliac "paving & cracking" technique for transcatheter aortic valve implantation.

Challenging femoral/iliac access (CA) can lead to vascular complications which can hamper the clinical benefit of transfemoral (TF) transcatheter aortic valve implantation (TAVI). In this sense, iliac artery rupture is a severe complication associated with significant morbidity and mortality. We report a case of TF-TAVI managed with the "paving and cracking technique" to overcome CA.

Overinflation of balloon-expandable valves for transcatheter treatment of pure noncalcified native aortic regurgitation: How much oversizing is needed and achievable?

Transcatheter aortic valve implantation (TAVI) in noncalcified pure aortic valve regurgitation is challenging as dedicated valves are not widely available. We present a case series of four inoperable patients who underwent compassionate TAVI for this indication at our institution with a balloon-expandable valve. In this context, we analyzed the relevant technical aspects such as the need for larger oversizing of the transcatheter prosthesis and the safety and limits of valve overexpansion.

Pattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people.

STUDY DESIGN: To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by 18F-Fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET). METHODS: We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent 18F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBRmax). The independent relationships between HIV status and both TBRmax and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD). RESULTS: Unadjusted mean TBRmax in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBRmax in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001). CONCLUSIONS: In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBRmax in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.

Gender-related differences in changes of estimated bleeding risk in patients on dual antiplatelet therapy: the RE-SCORE multicenter prospective registry.

The risk of bleeding as predicted by the PRECISE-DAPT score can vary over time after percutaneous coronary intervention (PCI). We sought to compare the predictive ability of the PRECISE-DAPT score calculated at baseline and reassessed during follow-up in male and female patients undergoing PCI. The RE-SCORE was a multicenter, prospective registry including patients undergoing PCI treated with dual antiplatelet therapy (DAPT) for 1 year. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The PRECISE-DAPT score was determined for each patient at the time of PCI and at 1, 4 and 8-month follow-up visits or before the occurrence of an endpoint event. A total of 480 patients undergoing PCI were included. At baseline, median PRECISE-DAPT score was similar in males (23.2 [IQR 20.1-24.2]) and females (23.4 [IQR 20.2-25.3]; p = .22). During follow-up, an increase in the PRECISE-DAPT occurred significantly more often in females (44%) than in males (23%; p < .001). The discrimination of the PRECISE-DAPT score calculated at baseline was marginal in both males (c-index = 0.59, 95% CI: 0.51-0.65) and females (c-index = 0.55, 95% CI: 0.49-0.60). The discriminative ability of the score reassessed at follow-up was excellent in females (c-index = 0.84; 95% CI: 0.77-0.91) but remained modest in males (c-index = 0.61; 95% CI: 0.55-0.70). The bleeding predictive ability of the PRECISE-DAPT score can vary over time, more commonly in females than males. The discrimination of the score calculated during follow-up appeared improved in females but remained modest in males.Clinical Trial Registration - ClinicalTrials.gov Identifier: NCT03526614.

Coronary artery disease and reasonably incomplete coronary revascularization in high-risk patients undergoing transcatheter aortic valve implantation.

OBJECTIVES: To evaluate the long-term impact of coronary artery disease (CAD) and heart team-guided incomplete coronary revascularization in patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND: Revascularization strategy of CAD diagnosed with routine coronary angiography before TAVI is uncertain. METHODS: Five hundred and forty consecutive TAVI patients were classified as having CAD or normal coronary arteries (no-CAD). Within the CAD group, patients were further classified as those with complete (CR) versus incomplete revascularization (IR). Revascularization strategy was guided by the Heart Team following an algorithm largely based on current guidelines. Main outcome of interest was the incidence of 5-year cardiovascular (CV) death. RESULTS: Prevalence of CAD was 53.9%. CAD patients showed significantly lower left ventricular ejection fraction (LVEF: 55.8 ± 13.4% CAD vs. 61.4% ± 12.1 no-CAD, p < .0001), lower gradients, and larger ventricular volumes in comparison with the no-CAD group. Within the CAD group, 138 patients (47.4%) received CR and 153 (52.6%) IR. In-hospital mortality was 3.9%, without significant difference between groups (4.0% no-CAD vs. 3.8% CAD, p = .88; 2.9% CR vs. 4.6% IR, p = .45). Median follow-up was 57.8 months. Five-year survival free from CV death was 79.6% in the CAD versus 77.9% in the no-CAD group (p = .98), and 84.3% in the CR versus 74.3% in the IR groups (p = .25). These results were confirmed excluding patients with previous revascularization. At multivariable analyses, presentation with acute coronary syndrome (ACS) was significantly associated with 5-year CV death. CONCLUSIONS: CAD is frequent in patients undergoing TAVI but portends an adverse prognosis only when presenting with ACS. Heart-team directed complete or reasonably incomplete revascularization was associated with comparable outcomes.

Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. METHODS: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk. FINDINGS: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. INTERPRETATION: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. FUNDING: None.

Efficacy and safety of dual antiplatelet therapy after coronary stenting in patients with chronic kidney disease.

BACKGROUND: We compared efficacy and safety of short- (3 or 6 months) versus long-term (≥12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation, according to the presence of chronic kidney disease (CKD). METHODS: Patient-level pooled analysis was performed with 7242 patients (87.2% with 2nd generation DES) from 5 randomized controlled trials. RESULTS: In both CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient-oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial infarction [MI], stroke and TIMI major bleeding) were not different between the short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD population). The rates of coronary thrombotic events (any MI and definite/probable stent thrombosis) also did not differ between short- and long-term DAPT in either CKD or non-CKD population. As for bleeding events, long-term DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non-CKD population. The similar trend was observed with long-term DAPT in CKD population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64-15.63, P=.160). CONCLUSIONS: The rates of POCO and coronary thrombotic events were significantly higher in patients with CKD compared with those without CKD, which were not affected by short- or long-term DAPT. Higher bleeding incidence by long-term DAPT was only observed in non-CKD patients but not in CKD patients. Further large scale studies are warranted to confirm our findings.

Systemic inflammatory status is associated with increased platelet reactivity in the early period after acute coronary syndromes.

Systemic inflammation measured by high-sensitivity C reactive protein (CPR) is associated with increased risk of major adverse cardiovascular events (MACE). Recent clinical trials targeting CPR showed a reduction in MACE after an acute coronary syndrome (ACS). Inflammation could be linked to high platelet reactivity (HPR), which is an independent predictor of MACE in patients with ACS. We aimed to evaluate the impact of 1-month C-reactive Protein (CRP) levels on HPR in patients enrolled in the GEPRESS study. We measured CRP and platelet reactivity index (PRI) at 30 days follow-up. PRI was assessed with vasodilator stimulated phosphoprotein (VASP) phosphorylation assay at the same timepoint. HPR was defined as PRI >50%. Of the 1042 patients included in the GEPRESS study, 756 (75%) had both VASP and CRP data at 30 days follow-up. HPR was found in 61 (49.1%) patients with CRP >1 mg/L and 233 (36.4%) patients with CRP ≤1 mg/L, p = 0.012. After adjustment for covariates, we found a direct gradient of effect between CRP and HPR; the inclusion of CRP significantly increased the discrimination of HPR regression model. This is the first study showing that residual HPR is more likely to occur in patients with CRP >1 mg/L at 1 month after non-ST elevation-ACS and this may contribute to the unfavorable outcome observed in such patients.

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes.

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration. PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the ß coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p < 0.001] at baseline and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.

Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Aim: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results: We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions: Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Clinical outcomes with percutaneous coronary revascularization vs coronary artery bypass grafting surgery in patients with unprotected left main coronary artery disease: A meta-analysis of 6 randomized trials and 4,686 patients.

Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. METHODS: Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality (Pinteraction= .03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG (Pinteraction < .0001). Percutaneous coronary intervention was associated with greater rates of unplanned revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). CONCLUSIONS: In patients undergoing revascularization for ULMCAD, PCI was associated with similar rates of mortality compared with CABG at a median follow-up of 39 months, but with an interaction effect suggesting relatively lower mortality with PCI in patients with low SYNTAX score and relatively lower mortality with CABG in patients with high SYNTAX score. Both procedures resulted in similar long-term composite rates of death, myocardial infarction, or stroke, with PCI offering an early safety advantage and CABG demonstrating greater durability.

Short-versus long-term Dual Antiplatelet therapy after drug-eluting stent implantation in women versus men: A sex-specific patient-level pooled-analysis of six randomized trials.

BACKGROUND: Whether the efficacy and safety of dual antiplatelet therapy (DAPT) are uniform between sexes is unclear. We sought to compare clinical outcomes between short- (≤6 months) versus long-term (≥1 year) DAPT after drug-eluting stent (DES) placement in women and men. METHODS AND RESULTS: We pooled individual patient data from 6 randomized trials of DAPT (EXCELLENT, OPTIMIZE, PRODIGY, RESET, SECURITY, ITALIC PLUS). The primary outcome was 1-year risk of major adverse cardiac events (MACE). The main secondary outcome was 1-year risk of any bleeding. Out of the 11,473 randomized patients included in the pooled dataset, 3,454 (30%) were females. At 1-year follow-up, women had higher risk of MACE (3.6% vs. 2.8%; P = 0.01) but similar risk of bleeding (1.9% vs. 1.6%; P = 0.16) as compared with men. Compared with long-term DAPT, short-term DAPT was associated with similar rates of MACE in both women (HR 0.88; 95% CI 0.62-1.25) and men (HR 1.25; 95% CI 0.95-1.6; P interaction = 0.08)]. At 1-year follow-up, short-term DAPT was associated with lower rates of bleeding as compared with long-term DAPT in both women (HR 0.84; 95% CI 0.51-1.37) and men (HR 0.58; 95% CI 0.40-0.84; P-interaction = 0.25). The presence of MVD was associated with higher MACE rates in the short-term DAPT group in women (HR: 1.16; CI 0.60-2.23) and men (HR: 2.29; CI 1.22-4.29; P interaction = 0.25). CONCLUSIONS: Short-term DAPT is associated with similar rates of MACE but lower risk of bleeding when as compared with prolonged DAPT. There was no significant difference between sexes in the population studied. © 2016 Wiley Periodicals, Inc.

Effects of statin therapy on platelet reactivity after percutaneous coronary revascularization in patients with acute coronary syndrome.

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: conceptual evolution based on emerging evidence.

The objective of this article is to review the contemporary literature on optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) implantation. Relevant studies were searched through MEDLINE, the Cochrane database, and the EMBASE database. Of the 6852 publications retrieved, 23 were considered relevant, including 11 randomized controlled trials (RCTs) and 12 meta-analyses. Initially prescribed for 3-6 months after first-generation DES, the recommended duration of DAPT was subsequently prolonged to at least 1 year, a response to reports of late stent thrombosis after DAPT discontinuation. Seven RCTs subsequently suggested that 1-year DAPT may not be necessary after DES implantation, and that a 6-month or even a 3-month course of DAPT may be as effective and safer. In contrast, four RCTs examining the benefit of DAPT beyond 1 year reached conflicting conclusions. In the DAPT trial, 30-month compared with 12-month DAPT after DES resulted in reduced rates of stent thrombosis and major adverse cardiovascular events, but greater rates of major bleeding with increased non-cardiac mortality. Several meta-analyses have subsequently been performed collectively demonstrating increased rates of all-cause mortality with prolonged DAPT compared with shorter DAPT after DES, due to greater non-cardiovascular mortality with prolonged DAPT not offset by a concomitant reduction in cardiac mortality. The benefit-risk ratio of prolonged DAPT appears to be better in patients with myocardial infarction (MI) than in those without prior MI. On the basis of these findings, a personalized approach is advisable when deciding upon the optimal duration of DAPT after DES, wherein the individualized risks of ischaemic vs. bleeding events are carefully considered for each patient.

Risk stratification of patients undergoing medical therapy after coronary angiography.

AIM: We sought to investigate the prognostic impact of the SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) score (SS) on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) undergoing medical therapy only. METHODS AND RESULTS: Among the 13 819 patients enrolled in the ACUITY trial and undergoing coronary angiogram, 4491 patients were treated with medical therapy as the initial strategy. Of those, baseline SS and complete angiographic analysis were available in 1275 patients. Patients were divided in four groups based on the presence or absence of coronary artery disease (CAD) and subsequently, among patients with CAD, by SS. Major adverse cardiac events (MACE) and its individual components (death, myocardial infarction, and unplanned revascularization) were compared between groups. Among the 1275 patients, the mean SS was 3.5 ± 7.0 (range 0-45). SYNTAX score was 0 in 842 patients, >0 and ≤5 in 170, >5 and ≤11 in 119, and >11 in 144 patients. The 1-year rates of MACE were higher in patients with CAD and higher SS. By multivariable analysis, the SS was a strong predictor of all adverse ischaemic events, including mortality. By receiver operator characteristic analysis, an SS cut-off of 8 showed the best prognostic accuracy for death and MACE. CONCLUSION: In patients with NSTE ACS undergoing medical therapy, the SS, especially when >8, was shown to be a strong predictor of 1-year MACE, including mortality. This finding has important clinical implications for risk stratification of patients with NSTE ACS undergoing medical therapy after an initial angiogram.

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials.

BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. METHODS: We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. FINDINGS: We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. INTERPRETATION: Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. FUNDING: None.