Comparative prognostic value of C-reactive protein & fibrinogen in patients with coronary artery disease.

BACKGROUND & OBJECTIVES: The comparative prognostic value of C-reactive protein (CRP) and fibrinogen for cardiovascular events has been inconclusively investigated. t0 his study was carried out to compare the prognostic value of CRP versus fibrinogen in patients with coronary artery disease (CAD). METHODS: The study included 13,100 patients with coronary angiography-confirmed CAD. Plasma CRP and fibrinogen levels were measured before angiography in all patients. The levels of CRP>3 mg/l and fibrinogen>350 mg/dl were considered as elevated. The primary outcome was 1-year all-cause mortality. RESULTS: Patients were divided into four groups: patients with CRP≤3 mg/l and fibrinogen ≤350 mg/dl (n=4206); patients with CRP≤3 mg/l and fibrinogen >350 mg/dl (n=3132); patients with CRP>3 mg/l and fibrinogen ≤ 350 mg/dl (n=1273) and CRP >3 mg/l and patients with fibrinogen >350 mg/dl (n=4489). There were 634 deaths: 75 deaths in patients with CRP ≤3 mg/l and fibrinogen ≤350 mg/dl, 91 deaths in patients with CRP ≤3 mg/l and fibrinogen >350 mg/dl, 87 deaths in patients with CRP >3 mg/l and fibrinogen ≤350 mg/dl and 381 deaths in patients with CRP >3 mg/l and fibrinogen >350 mg/dl (Kaplan-Meier estimates of all-cause mortality, 1.8, 3.0, 7.0 and 8.7 %, log-rank test P<0.001). The multivariate analysis showed that CRP [adjusted hazard ratio (HR)=1.31, 95% confidence interval (CI) 1.18-1.45, for each standard deviation increase in the logarithmic scale] but not fibrinogen [adjusted HR=0.99 (0.90-1.09), for each standard deviation increase in the logarithmic scale] was an independent correlate of mortality. INTERPRETATION & CONCLUSIONS: The findings indicated that in patients with CAD, CRP was a better predictor of mortality than fibrinogen and offered prognostic information beyond that provided by the conventional cardiovascular risk factors.

Comparative efficacy of 2 zotarolimus-eluting stent generations: resolute versus endeavor stents in patients with coronary artery disease.

BACKGROUND: The Resolute zotarolimus-eluting stent (R-ZES) utilizes the same metallic platform and anti-restenotic drug as the Endeavor zotarolimus-eluting stent (E-ZES) but is coated with a more biocompatible polymer with enhanced drug-release kinetics. The aim of this study was to compare the long-term clinical outcomes of 2 zotarolimus-eluting stent generations. METHODS: In two randomized trials with broad inclusion criteria (ISAR-TEST 2 and ISAR-TEST 5), 1,000 patients were treated with R-ZES and 339 patients treated with E-ZES. In both trials follow-up angiography was scheduled at 6 to 8 months. The efficacy endpoint of interest was target lesion revascularization and the safety endpoints were the combined incidence of cardiac death or myocardial infarction related to target vessel as well as the incidence of definite stent thrombosis at 2-year follow-up. RESULTS: The incidence of target lesion revascularization at 2 years was 12.0% in the R-ZES group and 16.0% in the E-ZES (HR 0.72 [95% CI: 0.52-1.00], P = .052). The incidence of cardiac death or myocardial infarction was 5.5% vs. 4.8% (HR 1.15, [95% CI: 0.66-2.02], P = .62) and of definite stent thrombosis was 0.4% vs. 0.6% (HR 0.68, [95% CI: 0.12-3.72], P = .66), respectively. All measures of angiographic restenosis were in favor of the R-ZES; in-stent late lumen loss was 0.29 ± 0.56 with the R-ZES versus 0.58 ± 0.55 with the E-ZES (P < .0001). CONCLUSIONS: Comparison of the 2 Food and Drug Administration-approved zotarolimus-eluting stents suggested that the R-ZES as compared to the E-ZES displayed overall superior antirestenotic efficacy. Both devices were associated with a similar low risk of adverse safety events through 2 years.

Sex-related effectiveness of bivalirudin versus abciximab and heparin in non-ST-segment elevation myocardial infarction.

BACKGROUND: Female sex independently predicts bleeding risk after percutaneous coronary intervention (PCI). Bivalirudin is safer than abciximab plus heparin in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Thus, a greater benefit of bivalirudin in women would be expected. METHODS: We performed a sex-based analysis of the patients with NSTEMI (n = 1,721, 399 women) enrolled in the ISAR-REACT 4 trial and randomized to receive bivalirudin or abciximab plus heparin. Main outcome was a 30-day composite of death, large recurrent myocardial infarction, urgent target vessel revascularization, or major bleeding. Secondary outcome was 1-year composite of death, myocardial infarction, or target vessel revascularization. RESULTS: No difference in the main outcome was observed in groups with bivalirudin or abciximab plus heparin: 12.6% versus 15.5% (hazard ratio [HR] 0.81, 95% CI 0.48-1.37) among women and 10.6% versus 9.5% (HR 1.12, 95% CI 0.77-1.64) among men. Major bleeding occurred in 4.5% in the bivalirudin group versus 7.5% in the abciximab plus heparin group (HR 0.60, 95% CI 0.26-1.39) among women and 2.0% versus 3.8% (HR 0.52, 0.27-1.02) among men. At 1 year, the secondary outcome was observed in 24.1% in the bivalirudin group versus 28.7% in the abciximab plus heparin group among women, HR of 0.80 (95% CI 0.55-1.17), and in 20.6% and 19.0%, respectively, HR of 1.10 (95% CI 0.86-1.40) among men. CONCLUSION: Despite a higher peri-PCI bleeding risk in women, bivalirudin is as effective as and safer than abciximab plus heparin in women and men with NSTEMI undergoing PCI.

Uric acid and prognosis in angiography-proven coronary artery disease.

BACKGROUND: The optimal uric acid (UA) level associated with the lowest mortality and the strength of association between UA and mortality in various subgroups of patients with coronary artery disease (CAD) are unknown. MATERIALS AND METHODS: This study included 13 273 patients with angiographic confirmation of CAD and UA measurements available. The primary outcome analysis was 1-year mortality. RESULTS: Based on the receiver operating characteristic curve analysis, the best cut-off of UA for mortality prediction was 7·11 mg/dL. Using this cut-off, patients were divided into two groups: the group with UA ≤ 7·11 mg/dL (n = 9075) and the group with UA > 7·11 mg/dL (n = 4198). Cardiac mortality was 6·3% (256 deaths) in patients with UA > 7·11 mg/dL and 2·3% (201 deaths) in patients with UA ≤ 7·11 mg/dL [hazard ratio (HR) = 2·82, 95% confidence interval (CI) 2·36-3·36; P < 0·001]. After adjustment for cardiovascular risk factors, UA remained an independent correlate of cardiac mortality (HR = 1·20, 95% CI 1·08-1·34; P = 0·001, for each standard deviation increase in the logarithmic scale of UA). The relationship between cardiac or all-cause mortality and UA showed a J-shaped pattern with lowest mortality in patients with UA between 5·17 and 6·76 mg/dL. UA predicted mortality across all subgroups of patients, with strongest association in women and patients without arterial hypertension. CONCLUSIONS: UA predicted an increased risk of cardiac mortality across all subgroups of patients with CAD. The association between UA and cardiac or all-cause mortality had a 'J-shaped' pattern with lowest risk of death in patients with UA levels between 5·17 and < 6·76 mg/dL.

Prognostic value of uric acid in patients with Type 2 diabetes mellitus and coronary artery disease.

Studies investigating the prognostic role of UA (uric acid) in patients with Type 2 diabetes mellitus have given conflicting findings. We undertook the present study to assess the association between UA and outcome in patients with Type 2 diabetes mellitus and CAD (coronary artery disease). The study included 3705 patients with diabetes mellitus and angiography-proven CAD. UA was measured before coronary angiography. The primary outcome was 1-year all-cause mortality. The UA concentration [median (25th-75th quartiles)] was 6.44 mg/dl (5.40-7.70 mg/dl). There were 264 deaths (7.1%) during follow-up: 45 deaths in patients of the first UA quartile, 43 deaths in patients of the second UA quartile, 51 deaths in patients of the third UA quartile and 125 deaths in patients of the fourth UA quartile {Kaplan-Meier estimates of mortality, 5.1, 4.8, 5.6 and 14.0% respectively; unadjusted HR (hazard ratio), 2.81 [95% CI (confidence interval), 2.21-3.58]; P<0.001 for fourth quartile compared with first-third quartiles combined}. In the multivariable analysis, UA predicted all-cause mortality with an adjusted HR of 1.29 (95% CI, 1.12-1.48; P<0.001), for each S.D. increase in the logarithmic scale of UA level. The inclusion of UA in the multivariable model alongside known cardiovascular risk factors and other relevant variables increased the discriminatory power of the model regarding prediction of all-cause mortality [absolute and relative IDI (integrated discrimination improvement) 0.034 and 20.5% respectively; P<0.001]. In conclusion, in patients with Type 2 diabetes mellitus and confirmed CAD, elevated levels of UA predict mortality independently of known cardiovascular risk factors.

Five-year clinical outcomes of a polymer-free sirolimus-eluting stent versus a permanent polymer paclitaxel-eluting stent: final results of the intracoronary stenting and angiographic restenosis - test equivalence between two drug-eluting stents (ISAR-TEST) trial.

BACKGROUND: Limited evidence exists regarding the long-term performance of polymer-free (PF) drug-eluting stents (DES) in comparison to permanent polymer DES. This study investigated the 5-year efficacy and safety of a PF sirolimus-eluting stent (PF-SES) versus a permanent polymer paclitaxel-eluting stent (PES) in the setting of the Intracoronary Stenting and Angiographic Restenosis-Test Equivalence Between Two Drug-Eluting Stents (ISAR-TEST) randomized trial. METHODS AND RESULTS: A total of 450 patients undergoing percutaneous coronary intervention were randomized to receive either PF-SES (Yukon, Translumina; n = 225) or PES (Taxus, Boston Scientific; n = 225). Clinical follow-up was performed to 5 years after enrollment. The endpoints were major adverse cardiac events (MACE), target lesion revascularization (TLR), the composite of death or any myocardial infarction (MI) and stent thrombosis (ST). The incidence of MACE at 5 years was 27.3% (57 patients) in the PF-SES group and 31.7% (65 patients) in the PES group [hazard ratio (HR) = 0.87 [95% confidence interval (95% CI) = 0.61-1.24]; P = 0.40]. The combined incidence of death or MI was 16.6% (34 patients) in the PF-SES group and 20.0% (39 patients) in the PES group (HR = 0.86 [95% CI = 0.54-1.36]; P = 0.52). The incidence of TLR was 16.5% (34 patients) in the PF-SES group and 16.4% (33 patients) in the PES group (HR = 1.03 [95% CI = 0.64-1.66]; P = 0.89). ST occurred in 0.5% (one patient) in the PF-SES group and 1.6% (three patients) in the PES group (HR = 0.33 [95% CI = 0.03-3.14]; P = 0.32). CONCLUSION: Overall there was no significant difference in clinical outcomes between PF-SES and PES to 5 years. Extended follow-up supports the durability of efficacy and safety of PF-SES.

Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials.

AIMS: The aim of this study was to evaluate benefits and risks of extending dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in the drug-eluting stent era. METHODS AND RESULTS: We searched electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, chapters in books, and proceedings of advisory panels for the US Food and Drug Administration, for randomized controlled trials investigating the clinical impact of extending DAPT duration in patients undergoing PCI. The primary endpoint was all-cause death. The secondary endpoints were myocardial infarction (MI), stent thrombosis (ST), cerebrovascular accidents (CVAs), and thrombolysis in myocardial infarction (TIMI) major bleeding. We included four trials that randomized 8231 patients (50.2%, extended DAPT duration vs. 49.8%, control duration). A total of 8158 patients (99.1%) were available for final analyses. The median DAPT duration was 16.8 vs. 6.2 months for the extended DAPT and control groups, respectively. At follow-up (median 16.8 months) extending DAPT duration did not reduce all-cause death [odds ratio (95% confidence interval) = 1.15 (0.85-1.54), P = 0.36], MI [0.95 (0.66-1.36), P = 0.77], ST [0.88 (0.43-1.81), P = 0.73], or CVAs [1.51 (0.92-2.47), P = 0.10]. Conversely, extended DAPT duration clearly increased the risk of TIMI major bleeding [2.64 (1.31-5.30), P = 0.006]. CONCLUSIONS: The extension of DAPT duration after percutaneous coronary interventions may increase the risk of bleeding without reducing ischaemic events. These results need corroboration from large ongoing trials.

Intra-aortic balloon counterpulsation in patients with acute myocardial infarction without cardiogenic shock. A meta-analysis of randomized trials.

BACKGROUND: Conflicting data on intra-aortic balloon counterpulsation (IABC) as adjunctive therapy in high-risk acute myocardial infarction (AMI) without cardiogenic shock (CS) have been published. We performed a meta-analysis of randomized trials evaluating the benefits of IABC in patients with AMI without CS. METHODS: We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and relevant Web sites for randomized trials comparing IABC versus no IABC in patients with AMI without CS. No language, publication date, or publication status restrictions were applied. Primary end point was all-cause death. Secondary end points were congestive heart failure (CHF), reinfarction, recurrent myocardial ischemia, cerebrovascular accidents (CVA), and bleeding (moderate to severe) according to per protocol definitions. RESULTS: Six trials were included (1,054 patients, 49.1% IABC vs 50.9% no IABC). At follow-up, counterpulsation does not reduce all-cause death (4.4% vs 4.1%, odds ratio [OR] [95% CI] 1.11 [0.49-2.54], P = .80), CHF (17.1% vs 18%, OR 0.92 [0.43-1.96], P = .83), or reinfarction (5.3% vs 7.7%, OR 0.68 [0.23-1.76], P = .42). Intra-aortic balloon counterpulsation versus no IABC significantly reduces recurrent myocardial ischemia (3.6% vs 20.3%, OR 0.15 [0.08-0.28], P < .00001), but it increases the risk of CVA (2% vs 0.3%, OR 4.39 [1.11-17.36], P = .03) and bleeding (21.4% vs 16.1%, respectively, OR 1.46 [1.05-2.04], P = .02). CONCLUSIONS: Counterpulsation does not reduce death, CHF, or reinfarction in patients with AMI without CS. The significant reduction of recurrent myocardial ischemia associated with IABC use is offset by a higher risk of CVAs and bleeding.

Remodelling elective hospital services in the COVID-19 era - designing the new normal.

The provision of elective clinical services has decreased during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic to enable hospitals to focus on acute illness. Any end to the pandemic through widespread vaccination, effective treatment or development of herd immunity may be years away. Until then, hospitals will need to resume treating other diseases while also attempting to eradicate transmission of COVID-19 within the healthcare setting. In this article we suggest six major themes which could affect the design and delivery of elective clinical services: hospital avoidance, separation of high- and low-risk groups, screening, maintenance of adequate infection control, and new ways of working.

Proximal occlusion versus distal filter for cerebral protection during carotid stenting: updated meta-analysis of randomised and observational MRI studies.

AIMS: Proximal occlusion (PO) and distal filter (DF) serve for cerebral embolic protection during carotid artery stenting (CAS). New cerebral lesions at diffusion-weighted magnetic resonance imaging (DW-MRI) represent a surrogate endpoint for embolisation, though their clinical impact is controversial. We performed a meta-analysis of randomised and observational DW-MRI studies comparing PO and DF during CAS. METHODS AND RESULTS: We searched electronic scientific databases. The primary endpoint was the incidence of new cerebral lesions at DW-MRI; secondary endpoints were the incidence of new ipsilateral and new contralateral cerebral lesions at DW-MRI and death/cerebrovascular events (CVE). A total of 392 patients (seven studies) received CAS. At DW-MRI after 48 hours 178 patients (48.3%) presented new cerebral lesions. The use of PO versus DF reduced neither the risk of new cerebral lesions (OR [95% confidence interval] 0.65 [0.28-1.52], p=0.32) nor the risk of death/CVE (0.59 [0.22-1.60], p=0.30). Diabetes, baseline stenosis and symptoms significantly modified the risk estimates for new cerebral lesions. CONCLUSIONS: In this meta-analysis, one half of patients receiving protected CAS developed new embolic cerebral lesions at DW-MRI, although the overwhelming majority were asymptomatic. Cerebral protection with PO versus DF neither reduced cerebral embolisation nor impacted on clinical outcomes.

Long-term outcomes of biodegradable versus durable polymer drug-eluting stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of individual patient data from three randomised trials.

AIMS: Arterial plaque rupture and thrombus characterise ST-elevation myocardial infarction (STEMI) and may aggravate delayed arterial healing following durable polymer drug-eluting stent (DP-DES) implantation. Biodegradable polymer (BP) may improve biocompatibility. We compared long-term outcomes in STEMI patients receiving BP-DES vs. durable polymer sirolimus-eluting stents (DP-SES). METHODS AND RESULTS: We pooled individual patient-level data from three randomised clinical trials (ISAR-TEST-3, ISAR-TEST-4 and LEADERS) comparing outcomes from BP-DES with DP-SES at four years. The primary endpoint (MACE) comprised cardiac death, MI, or target lesion revascularisation (TLR). Secondary endpoints were TLR, cardiac death or MI, and definite or probable stent thrombosis. Of 497 patients with STEMI, 291 received BP-DES and 206 DP-SES. At four years, MACE was significantly reduced following treatment with BP-DES (hazard ratio [HR] 0.59, 95% CI: 0.39-0.90; p=0.01) driven by reduced TLR (HR 0.54, 95% CI: 0.30-0.98; p=0.04). Trends towards reduction were seen for cardiac death or MI (HR 0.63, 95% CI: 0.37-1.05; p=0.07) and definite or probable stent thrombosis (3.6% vs. 7.1%; HR 0.49, 95% CI: 0.22-1.11; p=0.09). CONCLUSIONS: In STEMI, BP-DES demonstrated superior clinical outcomes to DP-SES at four years. Trends towards reduced cardiac death or myocardial infarction and reduced stent thrombosis require corroboration in specifically powered trials.

Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography.

OBJECTIVE: Systematic investigation of restenosis after percutaneous coronary intervention (PCI) with bare metal stents (BMS) or first or second generation drug eluting stents (DES) in large scale, broadly inclusive patient populations undergoing follow-up angiography represents a gap in our scientific knowledge. We investigated the incidence of angiographically proven restenosis and its predictors in patients undergoing PCI with stents. METHODS: All patients undergoing successful implantation of coronary stents for de novo lesions from 1998 to 2009 and follow-up angiography at 6-8 months at two centres in Munich, Germany were eligible for inclusion. Patients with cardiogenic shock, dialysis dependent renal insufficiency or previous cardiac transplantation were excluded. Data were prospectively collected. The incidence of restenosis, defined as diameter stenosis ≥50% in the in-segment area at follow-up angiography, and its predictors were evaluated. RESULTS: A total of 12 094 patients met inclusion criteria. Angiographic follow-up was available for 10 004 patients (77.5%) with 15 004 treated lesions. Binary restenosis was detected in 2643 (26.4%) patients. Use of first generation DES versus BMS (OR 0.35, 95% CI 0.31 to 0.39) and second generation DES versus first generation DES (OR 0.67, 95% CI 0.58 to 0.77) were independent predictors of lower rates of restenosis. At multivariate analysis, smaller vessel size (OR 1.59, 95% CI 1.52 to 1.68, for each 0.5 mm decrease), total stented length (OR 1.27, 95% CI 1.21 to 1.33, for each 10 mm increase), complex lesion morphology (OR 1.35, 95% 1.21 to 1.51), presence of diabetes mellitus (OR 1.32, 95% 1.19 to 1.46), and history of bypass surgery (OR 1.38, 95% CI 1.20 to 1.58) were independently associated with restenosis and were similar across the spectrum of stent devices. CONCLUSIONS: In this large cohort of patients with angiographic surveillance we demonstrated the impact of device  development on antirestenotic efficacy, with sequentially improved efficacy from BMS to first generation DES to second generation DES. Predictors of restenosis were small vessel size, increased stented length, complex lesion morphology, diabetes mellitus, and prior bypass surgery.

Randomized comparison of biolimus-eluting stents with biodegradable polymer versus everolimus-eluting stents with permanent polymer coatings assessed by optical coherence tomography.

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43-2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA-possible markers of delayed arterial healing-were observed with similar frequency in both groups.

Prehospital statin therapy and one-year mortality in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Statins have multiple effects in patients with coronary artery disease. No studies have investigated whether chronic statin pretreatment before percutaneous coronary intervention (PCI) has an impact on long-term mortality in patients with stable angina. METHODS: The study included 8041 patients with stable angina. At the time of PCI, 5939 patients (73.8%) were receiving statins for ≥ 1 month before procedure and 2102 patients (26.2%) were not receiving statins. The primary outcome analysis was 1-year mortality. RESULTS: There were 192 deaths during the follow-up: 119 deaths among patients receiving statins and 73 deaths among patients not receiving statins (Kaplan-Meier estimates of 1-year mortality 2.06% and 3.59%; unadjusted hazards ratio [HR]=0.56, 95% confidence interval [CI] 0.42-0.75; P<0.001). Landmark analysis showed that almost all mortality benefit occurred in the first 30-days after PCI: 10 deaths among patients receiving statins and 22 deaths among patients not receiving statins (Kaplan-Meier estimates of 30-day death, 0.17% and 1.06%, respectively; HR=0.16, 95% CI 0.08-0.34, P<0.001). No significant difference in mortality according to statin pretreatment between 30 days and 1 year was observed (109 deaths among patients receiving statins vs 51 deaths among patients not receiving statins; Kaplan-Meier estimates 1.89% and 2.53%; HR=0.75, 95% CI 0.53-1.05, P=0.095). After adjustment in the Cox proportional hazards model, statin pretreatment was associated with a 35% reduction in the adjusted risk for 1-year mortality (adjusted HR=0.65, 95% CI 0.44-0.98, P=0.039). CONCLUSIONS: Pretreatment with statins before PCI was associated with a significant reduction of 1-year mortality in patients with stable angina.

Statin pretreatment and presentation patterns in patients with coronary artery disease.

BACKGROUND: Knowledge on the impact of pretreatment statin therapy on presentation of patients with coronary artery disease (CAD) is incomplete. The aim of this study was to investigate the impact of statin pretreatment on presentation patterns of patients with CAD. METHODS: The study included 12,989 consecutive patients with CAD who underwent coronary angiography. The primary outcome was presentation as stable angina or acute coronary syndrome (ACS) according to statin pretreatment. RESULTS: At the time of presentation, 8147 (62.7%) patients were receiving statins and 4842 (37.3%) patients were not receiving statins. Presentation pattern in patients receiving statins vs. those not receiving statins was: stable angina in 5939 (72.9%) vs. 2102 (43.4%) patients; odds ratio (OR) = 3.50, 95% confidence interval (CI) 3.25-3.78; p < 0.001; unstable angina in 1435 (17.6%) vs. 1011 (20.9%) patients; OR = 0.81, 95% CI 0.74-0.89; p < 0.001; non- -ST-segment elevation myocardial infarction (NSTEMI) in 463 (5.7%) vs. 505 (10.4%) patients; OR = 0.52, 95% CI 0.45-0.59; p < 0.001; and ST-segment elevation myocardial infarction (STEMI) in 310 (3.8%) vs. 1224 (25.3%) patients; OR = 0.11, 95% CI 0.10-0.13; p < 0.001. Gensini score (median [25th to 75th percentiles]) was significantly higher in patients on statins presenting with stable angina (26.5 [13.0-59.5] vs. 21.0 [10.5-47.4]; p < 0.001) or ACS (39.3 [17.5-77.0] vs. 37.0 [18.0-64.0]; p = 0.001). In multivariable analysis, statin therapy was an independent correlate of reduced presentation with ACS (adjusted OR = 0.35 [0.32-0.39]; p < 0.001) or STEMI (adjusted OR = 0.18 [0.16-0.22]; p < 0.001). CONCLUSIONS: Despite having a higher coronary atherosclerotic burden, patients with CAD on statin therapy have reduced odds for presentation with ACS and STEMI compared to patients not receiving statins.

Paclitaxel-coated balloon or primary bare nitinol stent for revascularization of femoropopliteal artery: a meta-analysis of randomized trials versus uncoated balloon and an adjusted indirect comparison.

BACKGROUND: The performance of paclitaxel-coated balloon (PCB) or primary bare nitinol stent (BNS) versus uncoated balloon angioplasty (UCB) for femoropopliteal artery disease and the relative efficacy and safety of PCB versus BNS are still debated. METHODS: A meta-analysis of trials in which patients were randomly assigned to PCB versus UCB or BNS versus UCB was performed, as well as an indirect comparison of PCB versus BNS, with UCB common comparator. The primary endpoint was target lesion revascularization (TLR); secondary endpoints were restenosis, death and amputation. RESULTS: In total, 1464 patients were assigned to revascularization with PCB versus UCB (n = 441) or BNS versus UCB (n = 1023). Treatment with PCB versus UCB reduced the risk of TLR (odds ratio [95% confidence interval] = 0.29 [0.15-0.56], p < 0.001) and restenosis (0.31 [0.19-0.51], p < 0.001) without affecting mortality (1.05 [0.41-2.71], p = 0.92) or amputation (0.68 [0.04-10.31], p = 0.78). BNS versus UCB therapy reduced the risk of TLR (0.46 [0.27-0.80], p = 0.006) and restenosis (0.51 [0.34-0.77], p = 0.02) without affecting mortality (2.08 [0.93-4.66], p = 0.07) or amputation (0.84 [0.30-2.35], p = 0.74). The indirect comparison found no difference with PCB versus BNS in the risk of TLR (0.63 [0.26-1.48] p = 0.29), restenosis (0.60 [0.32-1.15], p = 0.13) death (0.50 [0.05-4.82], p = 0.55) or amputation (0.80 [0.04-15.63], p = 0.66). CONCLUSIONS: In atherosclerotic disease of femoropopliteal artery, both PCB and BNS therapy have superior antirestenotic efficacy to UCB, without safety issues. At indirect comparison, PCB and BNS may have comparable antirestenotic efficacy and safety.

C-reactive protein and prognosis in women and men with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Sex-based differences in the association between C-reactive protein (CRP) and cardiovascular events in patients with coronary artery disease (CAD) are incompletely investigated. We investigated whether there are gender differences in the association between CRP and outcome in patients with CAD after percutaneous coronary intervention (PCI). METHODS: This study included 13,170 consecutive patients with CAD: 10,098 men and 3072 women. CRP was measured on admission in all patients. The primary outcome was 1-year mortality. RESULTS: CRP level (median [25th-75th percentiles]) was higher in women than in men (3.08 [1.30-8.37] mg/L vs 2.30 [0.92-6.47] mg/L; P<0.001). CRP was >3mg/L in 4250 men (42.1%) and 1554 women (50.6%; P<0.001). One-year mortality was 4.9% (n=641 deaths). Deaths occurred in 318 men with CRP >3mg/L and 122 men with CRP ≤3mg/L (mortality estimates 7.7% and 2.1%, P<0.001) and in 154 women with CRP >3mg/L and 47 women with CRP ≤3mg/L (mortality estimates 10.1% and 3.2%, P<0.001). After adjustment in the Cox model, CRP was associated with increased risk of mortality in women (adjusted hazard ratio [HR]=1.03, 95% confidence interval [CI] 1.01-1.04, P<0.001 for each 5mg/L increase) and in men (adjusted HR=1.02 [1.01-1.03], P<0.001, for each 5mg/L increase). CRP predicted mortality with an area under the receiver-operating characteristic curve =0.721, [0.683-0.760] in women and 0.732, [0.707-0.757] in men (P=0.659). CONCLUSIONS: Elevated CRP levels provide similar prognostic information in men and women with CAD after PCI which is independent and supplementary to that provided by conventional cardiovascular risk factors.

Relation of fibrinogen level with cardiovascular events in patients with coronary artery disease.

Evidence on the usefulness of fibrinogen for the risk stratification of patients with coronary artery disease remains inconclusive. The aims of this study were to investigate the association of fibrinogen with cardiovascular events and to assess whether this biomarker provides additional prognostic information on top of that provided by traditional cardiovascular risk factors. This study included 13,195 patients with angiography-proved coronary artery disease and fibrinogen measurements available. Receiver-operating characteristic curve analysis showed that the best fibrinogen cutoff for mortality prediction was 402.0 mg/dl. On the basis of this cutoff, patients were divided into 2 groups: the group with fibrinogen >402.0 mg/dl (n = 5,198) and the group with fibrinogen ≤402.0 mg/dl (n = 7,997). The primary outcome was 1-year mortality. All-cause deaths occurred in 393 patients with fibrinogen >402.0 mg/dl and in 246 patients with fibrinogen ≤402.0 mg/dl (Kaplan-Meier estimates of mortality 7.7% and 3.1%, log-rank test p <0.001). The relation between fibrinogen and mortality followed a J-shaped pattern, with lowest mortality in patients with fibrinogen concentrations of 295 to 369 mg/dl. After adjustment for cardiovascular risk factors and relevant clinical variables, fibrinogen remained an independent correlate of all-cause mortality (adjusted hazard ratio 1.07, 95% confidence interval 1.04 to 1.10, p <0.001, for each 50 mg/dl increase in fibrinogen level), but it did not improve the discriminatory power of the model for mortality prediction (integrated discrimination improvement 0.002, p = 0.32). In conclusion, in patients with coronary artery disease, fibrinogen is an independent correlate of mortality, but it does not provide additional prognostic information on top of that provided by traditional cardiovascular risk factors.

The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147) - a potential novel target in atherothrombosis prevention?

The immunoglobulin superfamily member EMMPRIN (CD147) plays an important role in a number of organ systems, including the cardiovascular system. Here we review the contemporary understanding of EMMPRIN and EMMPRIN-associated sequelae in the course of atherosclerosis. A significant body of data documents the pivotal role of EMMPRIN in the complex processes of atherogenesis, atheroprogression, and acute atherosclerothrombosis, a role that goes beyond that of a mere marker of inflammation.

Differential relative efficacy between drug-eluting stents in patients with bare metal and drug-eluting stent restenosis; evidence in support of drug resistance: insights from the ISAR-DESIRE and ISAR-DESIRE 2 trials.

AIMS: In drug-eluting stent (DES) restenosis, the contribution of drug hyporesponsiveness is poorly defined. We sought to evaluate if, in the setting of treatment for in-stent restenosis, the relative efficacy of sirolimus-eluting stents (SES) and of paclitaxel-eluting stents (PES) depends on the underlying substrate in which the stents are implanted, i.e., on whether the restenosis occurs within bare metal stents or within SES. METHODS AND RESULTS: We pooled data from the ISAR-DESIRE and ISAR-DESIRE 2 randomised trials and analysed outcomes in SES-treated and PES-treated patients. In all, 650 patients were included. Angiographic follow-up was available for 87% of patients. In SES-treated patients, both late loss (LL) and percentage diameter stenosis (%DS) were lower in patients treated for bare metal stent restenosis compared with SES restenosis (0.21±0.59 mm versus 0.41±0.66 mm, p=0.007; 27.6±19.4% versus 34.0±20.9%, p=0.015, respectively). In PES-treated patients, LL and %DS were similar in patients treated for bare metal stent restenosis compared with SES restenosis (0.48±0.59 mm versus 0.39±0.71, p=0.47; 33.5±22.2% versus 32.7±18.6%, p=0.75, respectively). Similarly, in terms of overall clinical efficacy, in SES-treated patients clinical outcomes were better in patients with bare metal stent restenosis compared with SES restenosis while in PES-treated patients outcomes were similar in both groups. At multivariate analyses the use of SES to treat restenosis within SES was predictive of both higher LL and %DS. CONCLUSIONS: The efficacy of sirolimus-eluting but not paclitaxel-eluting stents is significantly reduced when used for treatment of SES restenosis as compared to bare metal stent restenosis. The lower antirestenotic efficacy following SES implantation in patients with SES restenosis may support a role for drug resistance in restenosis within these stents.