Cardiovascular adverse events associated with smoking-cessation pharmacotherapies.

Smoking continues to be the leading cause of preventable deaths in the USA, accounting for one in every five deaths every year, and cardiovascular (CV) disease remains the leading cause of those deaths. Hence, there is increasing awareness to quit smoking among the public and counseling plays an important role in smoking cessation. There are different pharmacological methods to help quit smoking that includes nicotine replacement products available over the counter, including patch, gum, and lozenges, to prescription medications, such as bupropion and varenicline. There have been reports of both nonserious and serious adverse CV events associated with the use of these different pharmacological methods, especially varenicline, which has been gaining media attention recently. Therefore, we systematically reviewed the various pharmacotherapies used in smoking cessation and analyzed the evidence behind these CV events reported with these therapeutic agents.

Role of oral factor Xa inhibitors after acute coronary syndrome.

Despite an early invasive strategy and the use of dual antiplatelet therapy, patients with acute coronary syndrome (ACS) continue to be at substantial risk for recurrent ischemic events. It is believed that this risk is, at least in part, due to an intrinsic coagulation pathway that remains activated for a prolonged period after ACS. Earlier studies using warfarin showed a reduction in ischemic events, but the overall benefits were offset by increased bleeding complications. Recently, there has been increased interest in the potential role of new oral anticoagulants, some of which target factor Xa, after ACS. Factor Xa is important for the coagulation pathway and also plays a role in cellular proliferation and inflammation. It may thus be an attractive target for therapeutic intervention in ACS. Recently, various oral factor Xa inhibitors have been studied as potential treatment options for ACS. This review will focus on currently available data to evaluate the possible role of factor Xa inhibitors in the management of patients with ACS.

Pharmacologic rate versus rhythm-control strategies in atrial fibrillation: an updated comprehensive review and meta-analysis.

BACKGROUND: In patients with atrial fibrillation (AF), ventricular rate control with medications has been found to be noninferior in preventing clinical events, compared to a strategy converting patients to sinus rhythm and maintaining it with medications. Guidelines have accepted rate control as an acceptable therapeutic option. Most of the prior studies excluded patients without significant left ventricular dysfunction, or permanent AF. METHODS: The authors searched the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 to 2011. Trials included were direct head-to-head comparisons of rate- and rhythm-control strategy using pharmacological means. The primary outcome assessed was risk of all-cause mortality. We also assessed other pooled clinical endpoints using a random effects model (Mantel-Haenszel) between rate and rhythm-control strategies. RESULTS: Ten studies (total N = 7,867) met inclusion/exclusion criteria. In-hospital mortality was not different between groups (P = 0.31). The rates of stroke, systemic embolism, worsening heart failure, myocardial infarction, and bleeding were also similar. However, rates of rehospitalization were much lower with a rate-control strategy (P = 0.007). An exploratory analysis in patients younger than 65 years revealed a rhythm-control strategy was superior to rate control in the prevention of all-cause mortality (P = 0.0007). CONCLUSIONS: This systematic review suggests no difference in clinical outcomes with a rate or rhythm-control strategy with AF. However, rehospitalization rates appear to be lower with pharmacological rate control for all ages, while finding support for rhythm control in younger patients.

Timing and route of amiodarone for prevention of postoperative atrial fibrillation after cardiac surgery: a network regression meta-analysis.

BACKGROUND: We attempted to evaluate if an oral-only regimen was as effective in preventing postoperative atrial fibrillation (POAF) after cardiac surgery, in comparison to a regimen that included intravenous (IV) administration using a network meta-analysis of available data, and also attempted to assess if preoperative administration at least 1 day before surgery was superior to postoperative prophylaxis (at least 1 day after surgery). METHODS: We searched PubMed, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2011 that assessed rates of POAF with amiodarone. Finally an interaction odds ratio was computed to assess the efficacy of an oral-only regimen of amiodarone compared to one including IV administration and to evaluate if preoperative amiodarone was superior to postoperative prophylaxis. RESULTS: Twenty-three studies (total N = 3,950) were included. Both regimens of amiodarone improved risk of POAF; oral-only risk ratio (RR) was 0.59 (95% confidence interval [CI] 0.49-0.70; P < 0.01) and regimen including IV RR was 0.57 (95% CI 0.43-0.75, P < 0.01). The interaction odds ratio was 1.17 (95% CI 0.72-1.89, P = 0.533). Both preoperative amiodarone (P < 0.01) and postoperative prophylaxis were effective (P = 0.0009), irrespective of duration. CONCLUSIONS: This systematic review suggests a regimen of both oral-only and one including IV administration, as well pre- and postoperative administration of amiodarone is effective in prevention of POAF after cardiac surgery.

Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT).

BACKGROUND: This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial. METHODS AND RESULTS: Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients who only received an implantable cardioverter defibrillator (ICD) were significantly (P < 0.001) lower in LBBB patients (0.47; P < 0.001) than in non-LBBB patients (1.24; P = 0.257). The risk of ventricular tachycardia, ventricular fibrillation, or death was decreased significantly in CRT-D patients with LBBB but not in non-LBBB patients. Echocardiographic parameters showed significantly (P < 0.001) greater reduction in left ventricular volumes and increase in ejection fraction with CRT-D in LBBB than in non-LBBB patients. CONCLUSIONS: Heart failure patients with New York Heart Association class I or II and ejection fraction ≤ 30% and LBBB derive substantial clinical benefit from CRT-D: a reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias. No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances). CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Electrocardiographic changes in Takotsubo cardiomyopathy.

INTRODUCTION: Takotsubo cardiomyopathy (TC) is a unique transient nonischemic cardiomyopathy that mimics acute myocardial infarction (MI). The aim of our study was to evaluate electrocardiographic changes in patients with TC, including the frequency of ST elevation and other abnormalities. METHODS: Eleven patients were retrospectively identified from echocardiography database. All patients underwent coronary angiography and fulfilled the Mayo criteria for diagnosis of TC during the period November 2005 to September 2010. Standard 12-lead electrocardiograms recorded daily during the first week of hospitalization, after onset of symptoms were analyzed. RESULTS: Eight of 11 patients were found to have ST elevation, of which two patients had ST depression in reciprocal leads. No patient had ST elevation in lead V1, most likely reason being that wall-motion abnormalities in TC rarely extend to the region faced by lead V1. Pathological Q waves were found in five patients, of which two patients had transient Q waves, suggesting less myocardial damage. All 11 patients had T-wave inversion; eight of these patients had diffuse symmetric T-wave inversion, extending beyond the perfusion territory of any single coronary artery. QTc interval prolongation was found in 10 patients. All patients had left ventricular ejection fraction between 25% and 35% on presentation, which could not be predicted by the extent of electrocardiogram (ECG) changes. CONCLUSION: ECG changes in TC are distinctive and differ from those typically seen in acute anterior MI. The ECG abnormalities described may be important clues for the clinician to suspect diagnosis of TC in the right clinical setting.

Elevated troponin level is not synonymous with myocardial infarction.

BACKGROUND: Elevated troponin I in the absence of angiographically visible coronary lesions is seen in up to 10-15% of those undergoing angiography for suspected coronary artery disease. This study aims to elucidate the etiology of elevated cardiac troponin I in patients with normal coronary arteries on angiography. METHODS: We identified 1551 (8.6%) patients with normal coronary arteries from our catheterization database of 17,950 patients from Jan 2000 to Jun 2004. Elevated troponin I levels were found in 217 (14%) of 1551 patients with normal coronary arteries. Of these 217 patients, 73 surgical patients were excluded, and the remaining 144 patients formed the study population. The study population was compared with age and gender matched patients with myocardial infarction and coronary artery disease (Group II). RESULTS: The patients with elevated cardiac troponin I (cTnI) with normal coronary arteries had significantly lower prevalence of atherosclerotic risk factors and significantly higher left ventricular ejection fractions. The cTnI in patients with normal coronary arteries was elevated due to a number of causes including tachycardia, myocarditis, pericarditis, severe aortic stenosis, gastrointestinal bleeding, sepsis, left ventricular hypertrophy, severe congestive heart failure, cerebrovascular accident, electrical trauma, myocardial contusion, hypertensive emergency, myocardial bridging, pulmonary embolism, diabetic ketoacidosis, chronic obstructive pulmonary disease exacerbation and coronary spasm. CONCLUSIONS: Cardiac troponin I could be elevated in a number of conditions, apart from acute myocardial infarction, and could reflect myonecrosis. Acute myocardial infarction is a clinical diagnosis as the laboratory is an aide to, not a replacement for, informed decision making.

Isolated and significant left main coronary artery disease: demographics, hemodynamics and angiographic features.

Left main coronary artery disease carries a poor prognosis. The etiology of isolated and significant left main coronary artery (ILMCA) disease is not well understood. Studies so far were limited by small numbers. The authors identified 46 patients with ILMCA disease from their database over 10 years (group I) and compared them with 83 consecutive patients undergoing catheterization (group II). They also compared patients with ostial vs distal ILMCA disease. Group I represented 0.1% of catheterization patients. The demographic profile and atherosclerotic risk factor profile of the 2 groups as well as ostial and distal ILMCA disease were compared. This is the largest study of ILMCA disease. Risk factors for atherosclerosis were commonly seen. Nonatherosclerotic causes of ILMCA disease were not seen. This study suggests coronary atherosclerosis as the predominant cause of ILMCA disease. ILMCA disease is more common in women. Diabetes is more commonly associated with distal ILMCA lesion. There is a trend suggesting that ostial ILMCA lesion is more common in smokers and women.

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Relationship between intermittent claudication, inflammation, thrombosis, and recurrent cardiac events among survivors of myocardial infarction.

BACKGROUND: Among coronary disease patients, concomitant peripheral arterial disease is a potent risk factor for future cardiac events and mortality. We sought to determine clinical and biochemical markers that might better elucidate the relationship between coronary and peripheral arterial disease. METHODS: Two months after an index myocardial infarction, 1045 patients provided detailed medical histories and underwent blood testing for selected hemostatic, lipid, and inflammatory markers. Patients were then followed up prospectively for a mean of 26 months. RESULTS: Compared with individuals without intermittent claudication (n = 966), those with claudication (n = 78) (information was unavailable for 1 individual) were significantly older and demonstrated an increased frequency of diabetes mellitus, tobacco use, prior cardiac and cerebrovascular events, and depressed left ventricular function. Individuals with claudication were less likely to receive beta-blocker therapy after the index infarction. Individuals with claudication had evidence of enhanced procoagulant and proinflammatory states manifested by relative elevations in plasma fibrinogen, D-dimer, C-reactive protein, and serum amyloid A concentrations. During follow-up, the presence of claudication was associated with an independent 2-fold increase in the combined end point of death or nonfatal cardiac event (38.5% vs 17.8%, P =.001) and a 5-fold increase in cardiac mortality (19.2% vs 3.6%, P =.001). Patients with intermittent claudication who were not treated with beta-blockers had a significant 3-fold mortality excess relative to those receiving beta-blockers. CONCLUSIONS: Following myocardial infarction, the added presence of intermittent claudication is associated with heightened procoagulant and proinflammatory states and an underuse of beta-blocker therapy and is a strong independent predictor of recurrent cardiovascular events.

Improving clinical practice guidelines for practicing cardiologists.

Cardiac-related clinical practice guidelines have become an integral part of the practice of cardiology. Unfortunately, these guidelines are often long, complex, and difficult for practicing cardiologists to use. Guidelines should be condensed and their format upgraded, so that the key messages are easier to comprehend and can be applied more readily by those involved in patient care. After presenting the historical background and describing the guideline structure, we make several recommendations to make clinical practice guidelines more user-friendly for clinical cardiologists. Our most important recommendations are that the clinical cardiology guidelines should focus exclusively on (1) class I recommendations with established benefits that are supported by randomized clinical trials and (2) class III recommendations for diagnostic or therapeutic approaches in which quality studies show no benefit or possible harm. Class II recommendations are not evidence based but reflect expert opinions related to published clinical studies, with potential for personal bias by members of the guideline committee. Class II recommendations should be published separately as "Expert Consensus Statements" or "Task Force Committee Opinions," so that both majority and minority expert opinions can be presented in a less dogmatic form than the way these recommendations currently appear in clinical practice guidelines.

Giving IV and oral amiodarone perioperatively for the prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass surgery: the GAP study.

PURPOSES: We studied the use of perioperative IV and oral administration of amiodarone for the prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: In the United States, > 500,000 patients undergo CABG each year. Numerous studies to date have suggested that postoperative atrial fibrillation occurs in 30 to 50% of patients, leading to significant morbidity, including hypotension, heart failure, thromboembolic complications, prolonged hospital stay, and increased hospital costs. The objective of this study was to assess the use of IV amiodarone in combination with oral amiodarone to reduce the incidence of postoperative atrial fibrillation. METHOD: From January 1999 to October 1999, 51 patients scheduled for CABG were randomly selected for participation in the amiodarone administration trial. IV amiodarone, 0.73 mg/min, was administered on call to the operating room for 48 h, followed by oral amiodarone, 400 mg q12h, for the next 3 days. The amiodarone group was case-control matched to the incidence of postoperative atrial fibrillation in 92 patients undergoing CABG using conventional medical therapy during the same period. The primary end point of this study was the incidence of postoperative atrial fibrillation, length of hospital stay, and hospital costs, compared to the control group undergoing CABG during the same time. RESULTS: Atrial fibrillation occurred in 3 of 51 patients (5.88%) in the amiodarone group, compared to 24 of 92 patients (26.08%) in the control group. Length of hospital stay in the amiodarone group was less than in the control group (5.3 days vs 6.7 days), with a trend toward decrease in hospital costs. CONCLUSION: The administration of IV amiodarone in conjunction with oral amiodarone for a total dose of 4,500 mg over 5 days appears to be a hemodynamically well-tolerated, safe, and effective treatment in decreasing the incidence of postoperative atrial fibrillation, shortening length of stay, and a trend toward lowering hospital costs, even in patients with significantly reduced left ventricular function (< 30%). A large multicenter study using IV and oral amiodarone should be pursued prior to deciding whether its use should become standard therapy in all patients undergoing CABG in order to decrease the incidence of postoperative atrial fibrillation.

Comparable benefit of ß-blocker therapy in heart failure across regions of the world: meta-analysis of randomized clinical trials.

BACKGROUND: There is a concern about geographical region heterogeneity regarding clinical benefit of ß-blocker (BB) therapy in heart failure with reduced ejection fraction (HFrEF). This study sought to compare benefits of BB use within randomized controlled trials (RCTs) that enrolled patients with HFrEF from North America (NA) compared with other regions of the world (ROW). METHODS: We conducted a meta-analysis using MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus (inceptions-December 2012) of BB RCTs stratified according to NA vs ROW. The primary end point was all-cause mortality and secondary end points were cardiovascular death, sudden death, death due to pump failure, and premature drug discontinuation. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for each outcome were calculated with interaction terms for region. Two-sided P values were calculated with P < 0.05 considered significant. RESULTS: The analysis included 16 RCTs with 14,452 patients; 7 trials were conducted in NA and 9 trials in ROW with follow-up durations of 3-58 months. All-cause mortality was consistently reduced in NA (OR, 0.82; 95% CI, 0.71-0.96; P = 0.01) and ROW (OR, 0.76; 95% CI, 0.69-0.84; P < 0.001; P-interaction = 0.40). Overall and according to region, all secondary end points including premature drug discontinuation were also less with BB therapy (P-interactions all ≥ 0.10). CONCLUSIONS: For the regions represented in the included trials, there is no evidence to suggest that geographic region is a significant moderator of clinical outcomes with BB therapy in HFrEF patients.

Meta-analysis of global left ventricular function comparing multidetector computed tomography with cardiac magnetic resonance imaging.

We compare the diagnostic accuracy of multidetector row computed tomography (MDCT) to cardiac magnetic resonance imaging (CMR) for evaluating global left ventricular function. We systematically searched PubMed, CINAHL, Cochrane CENTRAL, Scopus, and the Web of Science databases for studies published between 1966 to January 2013 that compared left ventricle (LV) volumes, ejection fraction (EF) and LV mass measured by MDCT and CMR. We performed meta-analyses and used random-effects model with inverse variance weighting test to determine the overall bias and limits of agreement of LV end-diastolic volume, end-systolic volume, stroke volume, and EF measured by MDCT and CMR. Furthermore, subgroup analyses were performed to compare 16-slice and 64-slice MDCT with CMR. Two study authors independently reviewed the 90 articles originally identified and selected 27 studies (n = 831) for analysis. Excellent correlation and a linear relation were seen between MDCT and CMR for LV end-diastolic volume (r = 0.93; p <0.001), LV end-systolic volume (r = 0.95; p <0.001), LV stroke volume (r = 0.85; p <0.001), LV ejection fraction (r = 0.93; p <0.001), and LV mass (r = 0.86; p <0.001). Subgroup analyses showed strong positive correlations for both 16- and 64-slice MDCT. In conclusion, although not the first-line test for LV function assessment in most patients, when appropriate, retrospectively gated MDCT provides an accurate and valid assessment of LV function compared with CMR.

Relationship of body mass index with total mortality, cardiovascular mortality, and myocardial infarction after coronary revascularization: evidence from a meta-analysis.

OBJECTIVE: To investigate the relationship of body mass index (BMI) with total mortality, cardiovascular (CV) mortality, and myocardial infarction (MI) after coronary revascularization procedures (coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]). PATIENTS AND METHODS: Systematic search of studies was conducted using PubMed, CINAHL, Cochran CENTRAL, Scopus, and the Web of Science databases. We identified studies reporting the rate of MI, CV mortality, and total mortality among coronary artery disease patients' postcoronary revascularization procedures in various BMI categories: less than 20 (underweight), 20-24.9 (normal reference), 25-29.9 (overweight), 30-34.9 (obese), and 35 or more (severely obese). Event rates were compared using a random effects model assuming interstudy heterogeneity. RESULTS: A total of 36 studies (12 CABG; 26 PCI) were selected for final analyses. The risk of total mortality (relative risk [RR], 2.59; 95% CI, 2.09-3.21), CV mortality (RR, 2.67; 95% CI, 1.63-4.39), and MI (RR, 1.79; 95% CI, 1.28-2.50) was highest among patients with low BMI at the end of a mean follow-up period of 1.7 years. The risk of CV mortality was lowest among overweight patients (RR, 0.81; 95% CI, 0.68-0.95). Increasing degree of adiposity as assessed by BMI had a neutral effect on the risk of MI for overweight (RR, 0.92; 95% CI, 0.84-1.01), obese (RR, 0.99; 95% CI, 0.85-1.15), and severely obese (RR, 0.93; 95% CI, 0.78-1.11) patients. CONCLUSION: After coronary artery disease revascularization procedures (PCI and CABG), the risk of total mortality, CV mortality, and MI was highest among underweight patients as defined by low BMI and CV mortality was lowest among overweight patients.

Risk of atrial fibrillation with use of oral and intravenous bisphosphonates.

Clinical studies suggest an association between bisphosphonate use and new-onset atrial fibrillation (AF). Intravenous bisphosphonates more potently increase the release of inflammatory cytokines than do oral bisphosphonates; thus, the risk of developing AF may be greater with intravenous preparations. We have evaluated incidence of new-onset AF with use of oral and intravenous bisphosphonates through a systematic review and meta-analysis of the literature. We searched PubMed, CINAHL, Cochrane Central Register of Controlled Trials, Scopus, and EMBASE databases for observational studies and randomized controlled trials (RCTs) published from 1966 to April 2013 that reported the number of patients developing AF with use of oral or intravenous bisphosphonates. The random-effects Mantel-Haenszel test was used to evaluate the relative risk of AF with use of oral and intravenous bisphosphonates. Nine studies (5 RCTs and 4 observational studies) were included in the final analysis. Pooled data from RCTs and observational studies (n = 135,347) showed a statistically significantly increased risk of new-onset AF with both intravenous (relative risk 1.40, 95% confidence interval 1.32 to 1.49) and oral (relative risk 1.22, 95% confidence interval 1.14 to 1.31) bisphosphonates. The z statistic, which assesses the difference between the 2 risk ratios, indicated higher risk of AF with intravenous bisphosphonates versus oral bisphosphonates (p = 0.03). In conclusion, pooled data from RCTs and observational studies suggest that risk of AF is increased by use of oral or intravenous bisphosphonates but further suggest that risk is relatively greater with intravenous preparations.

Prognosis and response to therapy of first inpatient and outpatient heart failure event in a heart failure clinical trial: MADIT-CRT.

AIMS: Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint. METHODS AND RESULTS: MADIT-CRT randomized patients with mild HF symptoms to resynchronization therapy vs. control with an average follow-up of 3.3 years and a total of 191 deaths. HF events were centrally adjudicated for receiving i.v. decongestive therapy in an outpatient setting, or an augmented HF regimen during a hospital stay. Patients were compared according to whether their first HF was an out- or inpatient event. The first primary event was non-fatal outpatient HF, non-fatal inpatient HF, and death in 52, 331, and 78 patients, respectively. Patients with inpatient HF tended to be older and more likely to have HF of ischaemic aetiology than subjects who developed outpatient HF events. The risk of death following either type of non-fatal HF events was extremely high [hazard ratio (HR) 12.4, 95% confidence interval (CI) 9.1-16.9 for inpatient HF; HR 10.7, 95% CI 6.1-18.7 for outpatient HF] compared with subjects without non-fatal HF events. Allocation to CRT-D was associated with significant reduction in both types of HF. CONCLUSION: Outpatient management of worsening HF portends a high risk of death, similar to inpatient HF events, and may be equally sensitive to the effects of therapy. These findings suggest that outpatient HF events should be considered in publicly reported outcomes measures and future HF clinical trials. TRIAL REGISTRATION: NCT01294449.

Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis.

BACKGROUND: The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists. METHODS: A systematic search of studies published between January 1, 1966, and March 31, 2012, was conducted using MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. English-language studies comparing blood transfusion with no blood transfusion or a liberal vs restricted blood transfusion strategy were identified. Two study authors independently reviewed 729 originally identified titles and abstracts and selected 10 for analysis. Study title, follow-up period, blood transfusion strategy, and mortality outcomes were extracted manually from all selected studies, and the quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology checklist. RESULTS: Studies of blood transfusion strategy in anemia associated with myocardial infarction were abstracted, as well as all-cause mortality rates at the longest available follow-up periods for the individual studies. Pooled effect estimates were calculated with random-effects models. Analyses of blood transfusion in myocardial infarction revealed increased all-cause mortality associated with a strategy of blood transfusion vs no blood transfusion during myocardial infarction (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P < .001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = .03). CONCLUSIONS: Blood transfusion or a liberal blood transfusion strategy compared with no blood transfusion or a restricted blood transfusion strategy is associated with higher all-cause mortality rates. A practice of routine or liberal blood transfusion in myocardial infarction should not be encouraged but requires investigation in a large trial with low risk for bias.

Intensive glucose control in diabetics with an acute myocardial infarction does not improve mortality and increases risk of hypoglycemia-a meta-regression analysis.

OBJECTIVES: Some early trials comparing intensive glucose control in type 2 diabetics with an acute myocardial infarction (MI) reported a decrease in mortality over a short period of follow up leading to a presumption of improved survival with intensive glucose control. Later data refuted this hypothesis. The 2009 ACC/AHA focused update on ST elevation MI gave a weak recommendation for the use of an insulin based regimen to achieve and maintain blood glucose less than 180 mg/dL. We decided to assess the validity of this recommendation. METHODS: The authors searched the Pub- Med, Cochrane CENTRAL and EMBASE databases for randomized controlled trials from 1965 through 2011.Trials included were direct head-to-head comparisons of an intensive blood glucose control strategy using pharmacological means (insulin in most cases) with a less intensive regimen. The primary outcome assessed was the risk of all -cause mortality in the two groups at the end of follow up. Also assessed was the rate of hypoglycemia. The methodological quality of the studies was assessed. Event rates were compared using a forest plot of relative risk (RR; 95% confidence interval [CI]) using a random effects model (Mantel-Haenszel) assuming inter-study heterogeneity. Statistical analysis was done with Review Manager V5.1 and SYSTAT. Meta-regression was done with duration of therapy as covariate. RESULTS: Three studies (total N = 2113) met the inclusion exclusion criteria. Mortality was not different between the groups (RR 0.94, 95% CI of 0.66-1.34; p=0.73.). Rate of hypoglycemia was significantly higher in the intensive glucose control group (RR 13.40, 95% CI 3.69-48.61; p < 0.01), with a 12% absolute risk increase and a number needed to harm (NNH) of 9 (95% CI 6.8- 9.8)-even without achieving target glycemic control. Neither did intensive control improve CHF, arrhythmias and reinfarction rates. Meta regression revealed that mortality with intensive glycemic control was worse with increased duration of therapy (p=0.001, for trend). CONCLUSIONS: This systematic review suggests limited benefit of intensive glycemic control in type 2 diabetics with an MI, with a significant risk of serious hypoglycemia.