Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease.

The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We sought to evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg). We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. In this pragmatic study, LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS. Study flow-chart. ASCVD atherosclerotic cardiovascular disease; CCS chronic coronary syndrome; ACS acute coronary syndrome; ASA acetylsalicylic acid; DAPT dual antiplatelet therapy; PCI percutaneous coronary intervention; NSAIDs nonsteroidal anti-inflammatory drugs; NERD NSAID-exacerbated respiratory disease; NECD NSAID-exacerbated cutaneous disease; NIUAA NSAID-induced urticaria-angioedema or anaphylaxis; SNIUAA single NSAID-induced urticaria-angioedema or anaphylaxis; SNIDHR single NSAID-induced delayed hypersensitivity reaction.

Management of multivessel coronary disease after ST-elevation myocardial infarction treated by primary coronary angioplasty.

Primary percutaneous coronary intervention of the infarct-related artery is now considered the gold standard for patients with acute ST-elevation myocardial infarction. However, a sizable portion of patients with ST-elevation myocardial infarction have concomitant multivessel disease, which raises important therapeutic and prognostic issues. Indeed, it is still unclear whether percutaneous coronary intervention of the culprit vessel alone is superior, equivalent, or inferior in terms of risk-benefit balance in comparison to a strategy of complete revascularization, with percutaneous coronary intervention of nonculprit vessels as well. The present systematic review provides an updated prospective on the rationale, background, and outcomes of culprit-only versus multivessel percutaneous revascularization in subjects undergoing primary percutaneous coronary intervention. Our findings clearly demonstrate that multivessel coronary disease significantly and adversely impacts on patient prognosis, yet a culprit-only revascularization strategy should be sought after in most cases, unless patient instability or symptoms/signs of residual myocardial ischemia support nonculprit vessel intervention.

International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences.

BACKGROUND: Acute pericarditis is common, yet uncertainty persists on its treatment. We thus aimed to conduct a comprehensive systematic review on pharmacologic treatments for acute or recurrent pericarditis. METHODS: Controlled clinical studies were searched in several databases and were included provided they focused on pharmacologic agents for acute pericarditis or its recurrences. Random-effect odds ratios (ORs) were computed for long-term treatment failure, pericarditis recurrence, rehospitalization, and adverse drug effects. RESULTS: From 2,078 citations, 7 studies were finally included (451 patients); but only 3 were randomized trials. Treatment comparisons were as follows: colchicine versus standard therapy (3 studies, 265 patients), steroids versus standard therapy (2 studies, 31 patients), low-dose versus high-dose steroids (1 study, 100 patients), and statins versus standard therapy (1 study, 55 patients). Colchicine was associated with a reduced risk of treatment failure (OR = 0.23 [0.11-0.49]) and recurrent pericarditis (OR = 0.39 [0.20-0.77]), but with a trend toward more adverse effects (OR = 5.27 [0.86-32.16]). Overall, steroids were associated with a trend toward increased risk of recurrent pericarditis (OR = 7.50 [0.62-90.65]). Conversely, low-dose steroids proved superior to high-dose steroids for treatment failure or recurrent pericarditis (OR = 0.29 [0.13-0.66]), rehospitalizations (OR = 0.19 [0.06-0.63]), and adverse effects (OR = 0.07 [0.01-0.54]). Data on statins were inconclusive. CONCLUSIONS: Clinical evidence informing decision-making for the management of acute pericarditis and its recurrences is still limited to few, small, and/or low-quality clinical studies. Notwithstanding such major caveats, available studies routinely using nonsteroidal anti-inflammatory agents in both experimental and control groups suggest a beneficial risk-benefit profile for colchicine and a detrimental one for steroids, especially when used at high dosages.

Infragenicular stent implantation for below-the-knee atherosclerotic disease: clinical evidence from an international collaborative meta-analysis on 640 patients.

PURPOSE: To report a systematic review of the literature published on the outcomes of stenting for below-the-knee disease in patients with critical limb ischemia (CLI). METHODS: Potentially relevant studies of stent implantation in the infragenicular arteries in >or=5 patients with >or=1-month follow-up were systematically sought in BioMedCentral, ClinicalTrials.gov, The Cochrane Collaboration Register of Controlled Trials (CENTRAL), Google Scholar, and PubMed. Data were abstracted and pooled with a random-effect model to generate risk estimates with 95% confidence intervals (CI). Interaction tests were performed to compare different stent types. A risk of bias assessment was conducted separately, as were appraisals for small study bias, statistical heterogeneity, and inconsistency. RESULTS: Eighteen nonrandomized studies were retrieved comprising 640 patients. After a median follow-up of 12 months, binary in-stent restenosis occurred in 25.7% (95% CI 11.6% to 40.0%), primary patency in 78.9% (95% CI 71.8% to 86.0%), improvement in Rutherford class in 91.3% (95% CI 85.5% to 97.1%), target vessel revascularization in 10.1% (95% CI 6.2% to 13.9%), and limb salvage in 96.4% (95% CI 94.7% to 98.1%). Head-to-head comparisons showed that sirolimus-eluting stents were superior to balloon-expandable bare metal stents in preventing restenosis and increasing primary patency (both p<0.001); sirolimus-eluting stents were also better than paclitaxel-eluting stents in terms of primary patency (p<0.001) and repeat revascularizations (p = 0.014). CONCLUSION: Percutaneous infragenicular stent implantation after failed or unsuccessful balloon angioplasty is associated with favorable clinical results in patients with CLI. Notwithstanding limitations of primary studies, sirolimus-eluting stents appear superior to bare metal and paclitaxel-eluting stents in terms of angiographic and/or clinical outcomes.

Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention.

BACKGROUND: Drug-eluting stents reduce the risk of restenosis after percutaneous coronary intervention (PCI) but may pose a risk of thrombosis. Cilostazol, an oral antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia, could hold the promise of preventing both restenosis and thrombosis. We systematically reviewed randomized clinical trials (RCTs) on the angiographic and clinical impact of cilostazol after PCI. METHODS: We searched RCT in BioMedCentral, CENTRAL, clinicaltrials.gov, EMBASE, and PubMed (November 2007). Coprimary end points were binary angiographic restenosis and repeat revascularization, abstracted and pooled by means of random-effect relative risks (RRs). Small study/publication bias was appraised with multiple methods. RESULTS: A total of 23 RCTs were included (5428 patients), with median follow-up of 6 months. Pooled analysis showed that cilostazol was associated with statistically significant reductions in binary angiographic restenosis (RR = 0.60 [0.49-0.73], P < .001) and repeat revascularization (RR = 0.69 [0.55-0.86], P = .001). Cilostazol appeared also safe, with no significant increase in the risk of stent thrombosis (RR = 1.35 [0.71-2.57], P = .36) or bleeding (RR = 0.71 [0.43-1.16], P = .17). However, small study bias was evident for both binary restenosis (P < .001) and repeat revascularization (P < .001), suggesting that at least part of the apparent benefits of cilostazol could be due to this type of confounding effect. CONCLUSIONS: Cilostazol appears effective and safe in reducing the risk of restenosis and repeat revascularization after PCI, but available evidence is limited by small study effects. Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients in which drug-eluting stents are contraindicated or when there is a need for neointimal hyperplasia inhibition.

A collaborative systematic review and meta-analysis on 1278 patients undergoing percutaneous drug-eluting stenting for unprotected left main coronary artery disease.

BACKGROUND: Cardiac surgery is the standard treatment for unprotected left main disease (ULM). Drug-eluting stent (DES) implantation has been recently reported in patients with ULM but with unclear results. We systematically reviewed outcomes of percutaneous DES implantation in ULM. METHODS: Several databases were searched for clinical studies reporting on > or = 20 patients and > or = 6-month follow-up. The primary end point was major adverse cardiovascular events (MACEs; ie, death, myocardial infarction, or target vessel revascularization [TVR]) at the longest follow-up. Incidence and adjusted risk estimates were pooled with generic inverse variance random-effect methods (95% CIs). RESULTS: From 823 initial citations, 16 studies were included (1278 patients, median follow-up 10 months). Eight were uncontrolled registries, 5 nonrandomized comparisons between DES and bare-metal stents and 3 nonrandomized comparisons between DES and CABG, with no properly randomized trial. Meta-analysis for DES-based PCI showed, at the longest follow-up, rates of 16.5% (11.7%-21.3%) MACE, 5.5% (3.4%-7.7%) death, and 6.5% (3.7%-9.2%) TVR. Comparison of DES versus bare-metal stent disclosed adjusted odds ratios for MACE of 0.34 (0.16-0.71), and DES versus CABG showed adjusted odds ratios for MACE plus stroke of 0.46 (0.24-0.90). Meta-regression showed that disease location predicted MACE (P = .001) and TVR (P = .020), whereas high-risk features predicted death (P = .027). CONCLUSIONS: Clinical studies report apparently favorable early and midterm results in selected patients with ULM. However, given their limitations in validity and the inherent risk for DES thrombosis, results from randomized trials are still needed to definitely establish the role of DES implantation instead of the reference treatment, surgery.

The hazards of discontinuing acetylsalicylic acid therapy in those at risk of coronary artery disease.

PURPOSE OF REVIEW: Drug compliance is important to maximize benefits and minimize risks; however, the importance of adherence to acetylsalicylic acid (i.e. aspirin) is pivotal in patients with or at risk of coronary artery disease. Given the recent developments in this research field, the high prevalence of coronary artery disease worldwide, and the intricacies of antiplatelet therapy after percutaneous coronary revascularization, we reviewed recent studies on aspirin discontinuation in those with or at risk of coronary artery disease. RECENT FINDINGS: Even in the most recent scientific literature, it appears clear that a sizable portion of patients at risk of coronary artery disease continue to discontinue aspirin during follow-up, either under physician's supervision or spontaneously. This fact has major adverse implications, as thrombotic events typically cluster early after aspirin discontinuation. Moreover, discontinuing aspirin appears hazardous for all patients with coronary artery disease, but such risk increases exponentially after percutaneous coronary intervention, especially with drug-eluting stents. SUMMARY: Life-long compliance to aspirin should be a major treatment goal in patients at risk of coronary artery disease, and supervised discontinuation of aspirin (e.g. before major noncardiac surgery) should last the minimum amount of time required and be bridged, when appropriate, by heparin therapy.

Next-generation drug-eluting stents in coronary artery disease: focus on everolimus-eluting stent (Xience V).

Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES), such as sirolimus-eluting (Cypher) and paclitaxel-eluting stents (Taxus), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor) and everolimus-eluting stents (Xience V), have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent.

Benefits of clopidogrel in patients undergoing coronary stenting significantly depend on loading dose: evidence from a meta-regression.

BACKGROUND: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its safety, but its optimal initial dosing is unclear. We performed a systematic review and meta-regression of randomized clinical trials comparing clopidogrel versus ticlopidine, focusing on clopidogrel front-loading. METHODS: PubMed was searched for pertinent studies (updated August 2006). Random-effect odds ratios (ORs) with 95% CIs were computed for death or nonfatal myocardial infarction, and weighted least squares random-effect meta-regression was performed to explore the impact of loading versus nonloading clopidogrel scheme. RESULTS: We retrieved 7 trials (3382 patients, average follow-up of 7 months). In 5 studies, both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (P for heterogeneity = .02) showed similar results for clopidogrel and ticlopidine (OR 0.90, 95% CI 0.44-1.84, P = .77). In studies administering clopidogrel with loading, this treatment was, however, significantly better than ticlopidine (OR 0.60, 95% CI 0.36-0.99, P = .05). This significant interaction between clopidogrel loading and its superiority in comparison with ticlopidine was also formally confirmed by meta-regression (beta = -0.64, P = .012). CONCLUSIONS: This work supports the superiority of a clopidogrel regimen including an initial loading dose in comparison with ticlopidine in patients undergoing coronary stenting.

Meta-analysis appraising high clopidogrel loading in patients undergoing percutaneous coronary intervention.

Combined antiplatelet treatment with aspirin and clopidogrel is pivotal to minimize periprocedural adverse events in patients who undergo percutaneous coronary intervention. However, there is debate on the best clopidogrel loading dose. The investigators performed a systematic review and meta-analysis of the optimal clopidogrel loading dose. Pertinent trials comparing high (>300 mg) and standard (300 mg) clopidogrel loading doses in patients scheduled for catheterization and/or percutaneous coronary intervention were systematically searched in BioMedCentral, CENTRAL, Google Scholar, and PubMed (December 2006). The primary end point was the 1-month rate of death or myocardial infarction. Secondary end points included other ischemic and bleeding adverse effects. Peto odds ratios were computed. A total of 10 studies (7 randomized, 3 nonrandomized) were included, enrolling 1,567 patients (712 loaded with 300 mg, 11 with 450 mg, 790 with 600 mg, and 54 with 900 mg). Overall, a high loading dose proved significantly superior to a standard loading dose in preventing cardiac death or nonfatal myocardial infarction (odds ratio 0.54, 95% confidence interval 0.32 to 0.90, p = 0.02), without any statistically significant increase in major or minor bleedings (p = 0.55 and p = 0.98, respectively). Sensitivity analysis restricted to randomized trials confirmed the superiority of a high loading dose regimen (p = 0.0031). Meta-regression disclosed a significant interaction between event rate and the benefits of high loading doses (p = 0.005), suggesting that the greater the underlying risk, the greater the favorable impact of a high loading dose. In conclusion, a high clopidogrel loading dose (>300 mg) significantly reduces early ischemic events in patients scheduled for percutaneous coronary intervention.

Ischemic cardiomyopathy, left coronary trunk hypoplasia and subsidiary coronary supply from the descending thoracic aorta.

Clinical symptoms of acute or chronic myocardial ischemia due to congenital coronary anomalies occasionally develop during adult life. While several types of coronary anomalies have been already reported, origin of the coronary arteries outside of the ascending aorta and pulmonary trunk is exceedingly rare, and has indeed been described to date only in a 6-day-old newborn. We hereby report to the best of our knowledge the first and unique case of an adult patient with ischemic cardiomyopathy, in whom coronary angiography and aortography disclosed both left main trunk hypoplasia and subsidiary left coronary supply provided by an ectopic artery arising from the descending thoracic aorta.

Inaccuracy of dipyridamole echocardiography or scintigraphy for the diagnosis of coronary artery disease in patients with both left bundle branch block and left ventricular dysfunction.

Non-invasive diagnosis of coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains challenging, and there is no consensus on the role of myocardial sesta-MIBI perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole echocardiography (dip-ECHO). We thus performed a prospective study to test the diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with concomitant LV dysfunction and LBBB, coronary angiography should be performed as the default diagnostic strategy in such patients.

Which Aspirin Dose and Preparation Is Best for the Long-Term Prevention of Cardiovascular Disease and Cancer? Evidence From a Systematic Review and Network Meta-Analysis.

The evidence base on aspirin in primary prevention suggests that it can reduce significantly the risk of cardiovascular disease (CVD) events and cancer, especially colorectal, albeit increasing bleeding. There is, however, uncertainty on the optimal aspirin dose and preparation for primary prevention. We thus aimed to review main sources of evidence informing on daily dosage and preparation of aspirin for primary prevention of CVD and cancer. We collected and elaborated aspirin effectiveness and safety data from U.S. Preventive Services Task Force reports on aspirin in primary prevention, distinguishing average daily dose in <100mg, 100mg, and >100mg. The following preparations were also systematically compared: enteric coated, controlled release, non-coated, or otherwise unspecified. Fixed-effect pairwise and network meta-analytic models were run in a frequentist framework. Eleven randomized trials were shortlisted, enrolling 104,101 subjects, followed for a median of 60months. At pairwise analysis, aspirin was associated with significant reductions in death and CVD events, non-significant reductions in cancer death or incidence, and significant increases in the risk of intracranial and gastrointestinal (GI) bleeding. An average daily dose of 100mg had the highest probability of reducing death, cancer death, and cancer incidence, whereas higher doses seemed superior for reducing CVD events, and 100mg or less daily proved better tolerated. Coated preparations appeared more beneficial for death, cancer death, cancer incidence, and GI bleeding, whereas controlled release preparations appeared better for CVD events and non-coated ones for intracranial bleeding. In conclusion, an average daily dose of 100mg of coated aspirin seems more likely to confer favorable preventive effects on death and cancer, with higher doses more appealing for CVD prevention and lower doses better tolerated.

Comparative safety and effectiveness of coronary computed tomography: Systematic review and meta-analysis including 11 randomized controlled trials and 19,957 patients.

BACKGROUND/OBJECTIVES: The clinical approach to suspected or established coronary artery disease (CAD) has been revolutionized in the last few decades by coronary computed tomography (coroCT). Yet, uncertainty persists on its comparative diagnostic and clinical effectiveness. We conducted a systematic review on randomized controlled trials (RCTs) of coroCT. METHODS: We searched RCTs in PubMed and The Cochrane Library, extracting as outcomes of interest long-term rates of death, myocardial infarction, revascularization, and invasive coronary angiography. Effects were estimated with risk ratios (RR) and 95% confidence intervals. RESULTS: A total of 11 trials were included, with 19,957 patients followed for a median of 6months. One trial focused on screening, 3 on stable CAD, and 7 on acute CAD. Meta-analysis showed that coroCT was associated with a trend toward fewer deaths or myocardial infarctions (RR=0.84 [0.70-1.01]) whereas no significant difference was found for the risk of death (RR=0.91 [0.71-1.18]). Conversely, the risk of myocardial infarction tended to be lower with coroCT at the overall analysis (RR=0.77 [0.59-1.02]), and this effect reached statistical significance in studies focusing on subjects with stable CAD (RR=0.69 [0.49-0.99]). These potential benefits were offset (or mediated) by a significant albeit modest increase in the need for invasive angiography (RR=1.36 [1.08-1.72]), and ensuing coronary revascularization (RR=1.76 [1.29-2.40]). CONCLUSIONS: According to the current evidence base, coroCT is associated with an increased usage of invasive angiography and coronary revascularization when compared to standard of care, with possible benefits on nonfatal myocardial infarction, but without significant benefits on death or the composite of death or myocardial infarction.

Long-term benefits of an early invasive management in acute coronary syndromes depend on intracoronary stenting and aggressive antiplatelet treatment: a metaregression.

BACKGROUND: Although recent data support an early invasive management in acute coronary syndromes (ACS), overall evidence appears conflicting. We performed a metaregression to explore the impact of intracoronary stenting and aggressive antiplatelet treatment on the risk/benefit ratio of an early invasive approach. METHODS: We searched several databases up to March 2004 for randomized trials comparing an early invasive versus delayed invasive or conservative management in ACS. Random-effects odds ratios were computed for death and/or myocardial infarction at the longest follow-up. Log (odds ratios) were tested for interaction with stenting and aggressive antiplatelet treatment (ie, glycoprotein IIb/IIIa inhibitors or thienopyridines in addition to aspirin). RESULTS: Ten trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early invasive management was associated with significantly reduced rates of death or myocardial infarction (P = .01). Metaregression analysis showed that the 2 most significant predictors of the benefits of an early invasive strategy in patients with ACS on event-free survival were the use, in subjects managed invasively, of aggressive antiplatelet treatment (P = .005) and stenting (P = .011). Moreover, both stenting and aggressive antiplatelet treatment were significantly associated with reduced mortality (respectively, P = .014 and P = .009) and correlated to each other (r = 0.76, P = .010). CONCLUSIONS: This study shows that the benefits of an early invasive approach in patients with ACS are significantly associated with concomitant aggressive antiplatelet treatment and stenting. These findings thus suggest the overall superiority of an early invasive approach in ACS, as long as state-of-the-art therapies are implemented.

Adjusted indirect comparison of intracoronary drug-eluting stents: evidence from a metaanalysis of randomized bare-metal-stent-controlled trials.

AIMS: Drug-eluting stents (DES) have been recently investigated, with favorable data for many devices, but comparative data are lacking. We thus performed an adjusted indirect comparison metaanalysis of DES. METHODS: Randomized trials comparing DES vs. bare-metal stents (BMS) were systematically searched, and random effect odds ratios (OR) were computed for target lesion revascularization (TLR) and binary in-stent restenosis rate (BRR) at 6-12 months. We then generated interaction OR for the comparison of different DES. RESULTS: We pooled data from 17 studies (allocating 3048 patients to BMS and 3392 to nine different DES). Indirect head-to-head comparison of sirolimus-eluting Cypher (N=1007) vs. polymeric paclitaxel-eluting Taxus (N=959) showed nonsignificant differences in TLR [OR=0.8 (0.5-1.4), p=0.45] but significant reductions in BRR favoring Cypher [OR=0.3 (0.1-0.6), p<0.001]. Everolimus-eluting stents appeared noninferior to Cypher or Taxus (p>0.50 for both TLR and BRR). Actinomycin-, mycophenolate-, and apolymeric paclitaxel-eluting stents (PES) all proved significantly worse than Cypher or Taxus for TLR or BRR. CONCLUSION: Notwithstanding its inherent limitations, the present metaanalysis confirms the effectiveness of both Cypher and Taxus, supports the promising role of everolimus-eluting stents, and suggests the significant inferiority of most other devices. These post hoc findings, albeit intriguing, await prospective confirmation.

State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews.

OBJECTIVES: To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. STUDY DESIGN AND SETTING: Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. RESULTS: After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P = 0.008) and showed more pronounced effect estimates (P = 0.002). Higher citations were associated with journal impact factor (P = 0.007), corresponding author from North America/Europe (P = 0.022), and inclusion of nonrandomized trials (P = 0.046). CONCLUSIONS: Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.

Nephropathy after administration of iso-osmolar and low-osmolar contrast media: evidence from a network meta-analysis.

BACKGROUND/OBJECTIVES: Contrast-induced nephropathy (CIN) may be a severe complication to the administration of iodine-based contrast media for diagnostic or interventional procedure using radiation exposure. Whether there is a difference in nephrotoxic potential between the various agents is uncertain. We aimed to perform a systematic review and network meta-analysis of randomized trials on iodine-based contrast agents. METHODS: Randomized trials of low-osmolar or iso-osmolar contrast media were searched in CENTRAL, Google Scholar, MEDLINE/PubMed, and Scopus. Risk of CIN was appraised within a hierarchical Bayesian model computing absolute rates (AR) and odds ratios (OR) with 95% credibility intervals, and probability of being best (Pbest) for each agent. RESULTS: A total of 42 trials (10048 patients) were included focusing on 7 different iodine-based contrast media. Risk of CIN was similarly low with iodixanol (AR=5.7% [2.2%-13.9%], Pbest=18.8%), iomeprol (AR=6.0% [2.2%-15.4%], Pbest=24.8%), iopamidol (AR=6.1% [2.2%-15.5%], Pbest=21.5%), and ioversol (AR=6.0% [2.1%-16.4%], Pbest=31.3%). Conversely, CIN was twice as common with iohexol (AR=11.2% [4.1%-29.5%], Pbest=0.1%) and ioxaglate (AR=11.0% [4.0%-26.9%], Pbest<0.1%), with both proving less safe than iodixanol (respectively OR=2.18 [1.22-3.92] and 2.05 [1.26-3.29]), iomeprol (OR=2.08 [1.04-4.17] and 1.96 [1.06-3.48]) and iopamidol (OR=2.04 [1.15-3.85] and 1.92 [1.06-3.45]). Data on iopromide were less conclusive (AR=6.9% [2.6%-17.1%], Pbest=3.6%). CONCLUSIONS: Iodixanol, iomeprol, iopamidol and ioversol are iodine-based contrast media with a similar renal safety profile. Iohexol and ioxaglate have a poorer renal safety profile, whereas further data may be required on iopromide.