Anasua Chakraborty

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.

IMPORTANCE Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation. OBJECTIVE To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism). DATA SOURCES PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014. STUDY SELECTION Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes. MAIN OUTCOMES AND MEASURES The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model. RESULTS Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92). CONCLUSIONS AND RELEVANCE Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.

Pre-procedural Elevated White Blood Cell Count and Neutrophil-Lymphocyte (N/L) Ratio are Predictors of Ventricular Arrhythmias During Percutaneous Coronary Intervention.

AIMS The absolute white blood cell (WBC) count and neutrophil to lymphocyte (N/L) ratio are predictors of death/myocardial infarction in patients who have undergone coronary angiography. We hypothesized that a pre-procedural elevated WBC count and an elevated N/L ratio would be a predictor of development of significant ventricular arrhythmias in subjects undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS We retrieved the data for all patients developing ventricular arrhythmia during PCI between 1999 to 2009 from our cath lab database (from 30,798 records), a total of 70 patients (Group I), and tabulated their WBC counts and absolute neutrophil and lymphocyte counts as well as N/L ratios. We compared the data with a random group of age, gender, medications and pre-existing condition matched controls (n=70) (Group II). We also adjusted for amount of myocardium under jeopardy. Group I had a significantly higher total WBC count (means 14,344 Vs 6852; 95% CI; p=0.0004); neutrophil count (means 75.79% Vs 58.06%; 95% CI; p < 0.0001) and N/L ratio (means 3.79 Vs 1.56; 95% CI; p < 0.0001) [means compared with t test]. CONCLUSION Our data suggests a pre-procedural elevated WBC count, neutrophils and elevated N/L ratio are predictors of significant ventricular arrhythmias in patients undergoing percutaneous coronary intervention (PCI).

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

Pulmonary embolism (PE) is a major cause of morbidity and mortality world-wide, and the use of thrombolytic therapy has been associated with favourable clinical outcomes in certain patient subsets. These potential benefits are counterbalanced by the risk of bleeding complications, the most devastating of which is intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from the 2003-2012 nationwide in-patient sample database (NIS) who received thrombolytics for PE. All patients with ICH during the PE hospitalisation were identified and a clinical risk score model was developed utilizing demographics and comorbidities. The dataset was divided 1:1 into derivation and validation cohorts. During 2003-2012, 176/9705 (1.8 %) patients with PE experienced ICH after thrombolytic use. Four independent prognostic factors were identified in a backward logistic regression model, and each was assigned a number of points proportional to its regression coefficient: pre-existing Peripheral vascular disease (1 point), age greater than 65 years (Elderly) (1 point), prior Cerebrovascular accident with residual deficit (5 points), and prior myocardial infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2 and ≥ 5 points were associated with ICH risks of 1.2 %, 1.9 %, 2.4 % and 17.8 %, respectively. Rates of ICH were similar in the validation cohort. The C-statistic for the risk score was 0.65 (0.61-0.70) in the derivation cohort and 0.66 (0.60-0.72) in the validation cohort. A novel risk score, derived from simple clinical historical elements was developed to predict ICH in PE patients treated with thrombolytics.

Statins and cognitive function: an updated review.

Ischemic heart disease remains the leading cause of death in the USA. Statins have substantially contributed to the decline in mortality due to heart disease. Historically, statins are hypothesized to be neuroprotective and beneficial in dementia, but recent reports have suggested an association with transient cognitive decline. We have critically appraised the relationship between statins and cognitive function in this review. Most of the data are observational and reported a protective effect of statins on dementia and Alzheimer’s disease in patients with normal cognition at baseline. Few studies, including two randomized control trials, were unable to find a statistically significant decrease in the risk or improvement in patients with established dementia or decline in cognitive function with statin use. As more randomized control trials are required to definitively settle this, cardiovascular benefits of statins must be weighed against the risks of cognitive decline on an individual basis.

Adherence to positive airway pressure therapy in hospitalized patients with decompensated heart failure and sleep-disordered breathing

STUDY OBJECTIVES Sleep-disordered breathing (SDB) has been implicated as a risk factor for the development of several adverse cardiovascular outcomes, but can be mitigated with positive airway pressure therapy (PAP). The nonadherence of patients with SDB on PAP in the outpatient setting ranges from 29% to 84%. However, adherence of PAP in patients with congestive heart failure (CHF) admitted for decompensated CHF and in whom SDB has been diagnosed in the hospital setting is not known. We hypothesized that despite a diagnosis in the hospital, the compliance of these patients with PAP therapy would not be different from the well-established adherence in patients with a diagnosis and treatment in the outpatient setting. METHODS The study was a retrospective analysis of patients admitted to an academic tertiary care hospital between March 2013 and February 2014. Patients presenting with decompensated CHF were screened and high-risk patients were started on PAP empirically and advised to undergo a postdischarge polysomnogram. Compliance of the patients with PAP was tracked for over 12 mo. Data from a similar outpatient group who underwent polysomnography during the study period were also reviewed. RESULTS Ninety-one patients underwent polysomnograhy postdischarge. Of the 91 patients, 81 patients agreed to PAP therapy. One patient was excluded as data were missing. The adherence at 3, 6, and 12 mo was 52%, 37%, and 27%, which was not significantly different than an outpatient control group. There was a trend for those with CHF plus SDB and compliant with PAP to have a higher probability of survival compared to those who were noncompliant (p = 0.07). CONCLUSIONS Adherence of patients to PAP therapy in whom a SDB diagnosis is made during acute hospitalization for heart failure is comparable to patients in the ambulatory setting. Adherence in first 3 mo is a predictive marker for improved survival trend.

Convergence in findings from randomized trials and elaborately analysed observational data on mortality reduction with carvedilol in heart failure in comparison with metoprolol

The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. This editorial refers to ‘Comparison of the clinical outcome of different beta-blockers in heart failure patients: a retrospective nationwide cohort study’, by R. Bølling et al., on page 678. Beta-blockers have been shown to reduce ‘clinically meaningful’ endpoints such as mortality, sudden cardiac arrest, and ventricular arrhythmias, and to lead to a decrease in rehospitalizations due to symptomatic heart failure with reduced ejection fraction (HFrEF); as well as to improve LV systolic function in both well-designed randomized trials1,2 and observational studies,3 including large meta-analyses.4 However, the choice of the optimal beta-blocker for management of HFrEF, in the midst of multiple available options of beta-blockers with varying properties and effects on the different adrenergic receptors, remains contentious. A recent, comprehensive meta-analysis5 had sought to evaluate this problem by means of a network meta-analysis of published, large randomized trials of beta-blockers in HFrEF, and found a ‘class effect’ for the clinical benefits seen with the different beta-blockers in HFrEF. In this issue of the European Journal of Heart Failure, Bølling et al. have performed an elaborate analysis to compare survival on different beta-blockers in heart failure.6 They analysed all Danish patients ≥35 years of age who were hospitalized with a first admission for HFrEF, and were initiated with a beta-blocker within 60 days of discharge. The analysis included 58 634 patients followed up for a mean period of 4.1 years. They found that patients receiving high dose carvedilol (≥50 mg/day) had a significantly lower risk of all-cause mortality than patients receiving high dose (≥200 mg/day) metoprolol. Risk of all-cause hospitalization was also reduced with use of high dose carvedilol, in comparison with high dose metoprolol. Also, in contrast to randomized data from the CIBIS group of trials,7 patients on a ≥10 mg/day dosage of

Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: An updated review of literature

Recent trials have highlighted the comparable mortality benefits and durability of the results for patients with severe aortic stenosis (AS) and high surgical risk managed with either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (AVR). Various national guidelines and international regulatory bodies have approved TAVR, thereby leading to potential wide usage and dissemination of this technique worldwide. Quality-of-life outcomes, in spite of being an important measure of success and acceptability of the procedure, have not been publicized as extensively. For high risk patients with severe AS, implementation of TAVR has resulted in comparable survival, but different and novel adverse events compared with AVR. We present an updated review focusing on the quality-of-life outcomes and issues with this new and important procedural approach.

ACP Journal Club. Review: More- vs less-intensive BP-lowering regimens reduce major CV events.

Question What are the efficacy and harms of more- vs less-intensive blood pressure (BP)lowering drug regimens? Review scope Included studies compared more- vs less-intensive BP-lowering drug regimens targeted to different BP levels or changes from baseline, and had 6 months of follow-up. Outcomes were a composite of major cardiovascular (CV) events (CV mortality, myocardial infarction [MI], stroke, or heart failure), components of the composite outcome, all-cause and non-CV mortality, end-stage kidney disease (ESKD), and adverse events. Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Library (all to Nov 2015); reference lists; and ClinicalTrials.gov were searched for randomized controlled trials (RCTs). 19 RCTs (n =44989, mean follow-up 3.8 y) met the inclusion criteria: 18 were done in adults (mean age 41 to 77 y, 37% to 74% men) and 1 in children (mean age 12 y, 59% boys). 13 RCTs included patients with hypertension alone or with other risk factors, 6 included patients with chronic kidney disease, 5 included those with diabetes, and 4 included patients with other risk factors. Trials had different BP targets. {13 had adequate allocation concealment; 3 blinded patients, 14 blinded outcome assessors, and 1 blinded study personnel}*; loss to follow-up ranged from 0% to 4.9%. Main results More-intensive regimens reduced BP compared with less-intensive regimens (weighted mean difference 6.8/3.5 mm Hg). More-intensive regimens reduced major CV events and strokes and had a borderline statistically significant benefit for MI compared with less-intensive regimens; groups did not differ for other clinical outcomes (Table). More- vs less-intensive regimens increased risk for severe hypotension (5 RCTs, n =10089, 0.3% vs 0.1% per patient-y, P =0.015); groups did not differ for serious adverse events related to BP lowering (6 RCTs, n =12265, 1.2% vs 0.9% per patient-y, P =0.112). Conclusion More- vs less- intensive blood pressurelowering regimens reduce major cardiovascular events and stroke. More- vs less-intensive blood pressurelowering regimens Outcomes Number of trials (n) Weighted event rates At a mean 3.8 y of follow-up More intensive Less intensive RRR (95% CI) NNT (CI) Major CV events 14 (43483) 4.9% 5.7% 14% (4 to 22) 126 (80 to 439) CV mortality 13 (42372) 1.6% 1.8% 9% (11 to 26) NS Myocardial infarction 13 (42389) 1.7% 1.9% 13% (0 to 24) NS Stroke 14 (43483) 2.0% 2.6% 22% (10 to 32) 175 (121 to 385) Heart failure 10 (33306) 0.9% 1.1% 15% (11 to 34) NS All-cause mortality 19 (44989) 3.5% 3.8% 9% (3 to 19) NS Non-CV mortality 12 (41993) 1.95% 1.99% 2% (13 to 14) NS ESKD 8 (8690) 5.8% 6.4% 10% (6 to 23) NS CV = cardiovascular; ESKD = end-stage kidney disease; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from relative risks and less-intensive regimen event rate in article using a random-effects model. CV mortality, myocardial infarction, stroke, or heart failure. Commentary In their meta-analysis, Xie and colleagues showed that some patients can benefit from more-intensive BP control for a composite CV endpoint (defined differently in the different trials), MI, and stroke. Heart failure, CV-related mortality, all-cause mortality, and ESKD were not significantly different between groups. Relative risks favored more-intensive BP-lowering regimens for reducing the composite CV endpoint across all populations other than in 2 trials of patients with CKD. Results did not differ by subgroups based on baseline comorbidities or baseline, target, or on-treatment BPs. Hypotension occurred infrequently overall but was more common in patients who received more-intensive treatment (0.3% vs 0.1% per patient-y). In nondiabetic patients at high CV risk and SBP 130 mm Hg, the SPRINT trial found that intensive BP lowering to a target <120 mm Hg was superior to routine management with a BP target <140 mm Hg for a composite of CV events, CV and all-cause mortality, and heart failure. The intensive strategy increased risk for hypotension, syncope, and electrolyte disorders and accelerated reductions in eGFR levels in patients without CKD at baseline. Unlike the results of the meta-analysis by Xie and colleagues, SPRINT found no statistically significant benefits for MI or stroke, which may have been due to limited statistical power for these outcomes. The results of SPRINT have implications for public health in terms of unmet treatment needs. However, patients in the more intensive treatment group required, on average, 1 additional antihypertensive drug to achieve BP goals, indicating a higher potential for adverse effects and increased expense. Benefits with intensive treatment for the composite CV outcome seen in patients 75 years of age (hazard ratio 0.67, 95% CI 0.51 to 0.86) warrant careful deliberation because of the potential for adverse effects in accord with primum non nocere. The possibly discordant results for MI and stroke in SPRINT compared with the Xie review and the ACCORD trial results in patients with diabetes (1) merit further exploratory analyses, most readily accomplished by adding SPRINT to the meta-analysis.

ACP Journal Club. In patients with SBP ≥ 130 mm Hg and CV risk, intensive vs standard BP control reduced CV events and mortality.

Question In patients with systolic blood pressure (SBP) 130 to 180 mm Hg and increased cardiovascular (CV) risk, does intensive vs standard BP-lowering treatment improve clinical outcomes? Methods Design Randomized controlled trial (Systolic Blood Pressure Intervention Trial [SPRINT]). ClinicalTrials.gov NCT01206062. Allocation Concealed.* Blinding Blinded* (outcome adjudicators). Follow-up period Median 3.26 years. The trial was stopped early for benefit (before the planned mean follow-up of 5 y). Setting 102 clinical centers in the USA. Patients 9361 patients 50 years of age (mean age 68 y, 64% men, mean BP 140/78 mm Hg) with SBP of 130 to 180 mm Hg and 1 CV risk factor. Exclusion criteria included diabetes mellitus or previous stroke. Intervention BP-lowering treatment to a target SBP <120 mm Hg (intensive treatment, n =4678) or to <140 mm Hg (standard treatment, n =4683). Outcomes Primary outcome was a composite of CV events (CV mortality, myocardial infarction, other acute coronary syndrome, stroke, or acute decompensated heart failure). Other outcomes included components of the primary outcome, all-cause mortality, renal outcomes, and serious adverse events. Patient follow-up 97% (intention-to-treat analysis). Main results The main results are in the Table. Intensive treatment reduced BP at 1 year more than standard treatment (mean difference 14.8/7.6 mm Hg). Conclusion In patients with systolic blood pressure 130 mm Hg and increased cardiovascular risk, intensive vs standard blood pressure control reduced a composite of cardiovascular events and all-cause mortality at a median 3.3 years. Intensive vs standard BP-lowering treatment in patients with systolic BP 130 to 180 mm Hg and increased CV risk Outcomes Event rates At a median 3.26 y Intensive Standard RRR (95% CI) NNT (CI) CV events 5.2% 6.8% 24% (11 to 35) 61 (42 to 138) CV mortality 0.8% 1.4% 43% (15 to 62) 167 (116 to 480) Myocardial infarction 2.1% 2.5% 17% (9 to 36) NS Stroke 1.3% 1.5% 11% (25 to 37) NS Heart failure 1.3% 2.1% 38% (16 to 55) 127 (87 to 301) All-cause mortality 3.3% 4.5% 27% (10 to 39) 84 (57 to 227) Composite renal outcome in patients with baseline CKD 1.05% 1.14% 11% (86 to 58) NS Injurious falls 2.2% 2.3% 4.4% (24 to 27) NS RRI (CI) NNH (CI) Acute coronary syndrome 0.86% 0.85% 0 (55 to 36) NS eGFR reduction in patients without baseline CKD 3.8% 1.1% 244% (142 to 399) 38 (23 to 64) Serious adverse events** 38% 37% 3.4% (2 to 9) NS Hypotension 2.4% 1.4% 67% (23 to 126) 107 (67 to 253) Syncope 2.3% 1.7% 34% (1 to 78) 173 (87 to 8199) Acute kidney injury or acute renal failure 4.1% 2.5% 65% (32 to 107) 62 (43 to 111) Electrolyte abnormality 3.1% 2.3% 35% (5 to 72) 127 (69 to 716) Bradycardia 1.9% 1.6% 19% (12 to 62) NS BP = blood pressure; CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated glomerular filtration rate; NS = not significant; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from hazard ratios and/or event rates in article. CV mortality, myocardial infarction, other acute coronary syndrome, stroke, or heart failure. 50% reduction in eGFR, long-term dialysis, or kidney transplantation. 2646 patients had CKD (eGFR <60 mL/min/1.73 m2) at baseline. 30% reduction to <60 mL/min/1.73 m2. **Fatal or life-threating events. Commentary In their meta-analysis, Xie and colleagues showed that some patients can benefit from more-intensive BP control for a composite CV endpoint (defined differently in the different trials), MI, and stroke. Heart failure, CV-related mortality, all-cause mortality, and ESKD were not significantly different between groups. Relative risks favored more-intensive BP-lowering regimens for reducing the composite CV endpoint across all populations other than in 2 trials of patients with CKD. Results did not differ by subgroups based on baseline comorbidities or baseline, target, or on-treatment BPs. Hypotension occurred infrequently overall but was more common in patients who received more-intensive treatment (0.3% vs 0.1% per patient-y). In nondiabetic patients at high CV risk and SBP 130 mm Hg, the SPRINT trial found that intensive BP lowering to a target <120 mm Hg was superior to routine management with a BP target <140 mm Hg for a composite of CV events, CV and all-cause mortality, and heart failure. The intensive strategy increased risk for hypotension, syncope, and electrolyte disorders and accelerated reductions in eGFR levels in patients without CKD at baseline. Unlike the results of the meta-analysis by Xie and colleagues, SPRINT found no statistically significant benefits for MI or stroke, which may have been due to limited statistical power for these outcomes. The results of SPRINT have implications for public health in terms of unmet treatment needs. However, patients in the more-intensive treatment group required, on average, 1 additional antihypertensive drug to achieve BP goals, indicating a higher potential for adverse effects and increased expense. Benefits with intensive treatment for the composite CV outcome seen in patients 75 years of age (hazard ratio 0.67, 95% CI 0.51 to 0.86) warrant careful deliberation because of the potential for adverse effects in accord with primum non nocere. The possibly discordant results for MI and stroke in SPRINT compared with the Xie review and the ACCORD trial results in patients with diabetes (1) merit further exploratory analyses, most readily accomplished by adding SPRINT to the meta-analysis.

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-Analysis

RESULTS Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92).