Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

Self-initiated lifestyle interventions lead to potential insight into an effective, alternative, non-surgical therapy for mitochondrial disease associated multiple symmetric lipomatosis.

BACKGROUND: A 56-year-old female, diagnosed as a carrier of the mitochondrial DNA mutation (MTTK c.8344A > G) associated with the MERRF (myoclonic epilepsy with ragged red fibers) syndrome, presented with a relatively uncommon but well-known phenotypic manifestation: severe multiple symmetric lipomatosis (MSL). After surgical resection of three kilograms of upper mid-back lipomatous tissue, the patient experienced a significant decline in her functional capacity and quality of life, which ultimately resulted in her placement on long-term disability. METHODS: Dissatisfied with the available treatment options centered on additional resection surgeries, given the high probability of lipoma regrowth, the patient independently researched and applied alternative therapies that centred on a carbohydrate-restricted diet and a supervised exercise program. RESULTS: The cumulative effect of her lifestyle interventions resulted in the reversal of her MSL and her previously low quality of life. She met all her personal goals by the one-year mark, including reduced size of the residual post-surgical lipomas, markedly enhanced exercise tolerance, and return to work. She continues to maintain her interventions and to experience positive outcomes at the two-year mark. INTERPRETATION: This case report documents the timing and nature of lifestyle interventions in relation to the reversal in growth pattern of her previously expanding and debilitating lipomas. The profound nature of the apparent benefit on lipoma growth demonstrates the intervention's potential as a new feasible non-surgical therapy for mitochondrial-disease-associated MSL, and justifies its systematic study. We also describe how this case has inspired the care team to re-examine its approach to involved patients.

Impact of a COPD comprehensive case management program on hospital length of stay and readmission rates.

BACKGROUND: COPD accounts for the highest rate of hospital admissions among major chronic diseases. COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing. AIM: The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD. MATERIALS AND METHODOLOGY: We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days. We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation. RESULTS: A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study. The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%. Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P<0.001). In addition, patients' mean LOS (days) for COPD-related admissions declined significantly from 10.8 to 6.8 (P<0.05). CONCLUSION: A comprehensive disease management program for COPD patients, including education, case management, and follow-up, was associated with significant reduction in hospital admissions and LOS.

Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care.

Chronic obstructive pulmonary disease (COPD) is a global health issue with high social and economic costs. Concomitant chronic cardiac disorders are frequent in patients with COPD, likely owing to shared risk factors (e.g., aging, cigarette smoke, inactivity, persistent low-grade pulmonary and systemic inflammation) and add to the overall morbidity and mortality of patients with COPD. The prevalence and incidence of cardiac comorbidities are higher in patients with COPD than in matched control subjects, although estimates of prevalence vary widely. Furthermore, cardiac diseases contribute to disease severity in patients with COPD, being a common cause of hospitalization and a frequent cause of death. The differential diagnosis may be challenging, especially in older and smoking subjects complaining of unspecific symptoms, such as dyspnea and fatigue. The therapeutic management of patients with cardiac and pulmonary comorbidities may be similarly challenging: bronchodilators may have cardiac side effects, and, vice versa, some cardiac medications should be used with caution in patients with lung disease. The aim of this review is to summarize the evidence of the relationship between COPD and the three most frequent and important cardiac comorbidities in patients with COPD: ischemic heart disease, heart failure, and atrial fibrillation. We have chosen a practical approach, first summarizing relevant epidemiological and clinical data, then discussing the diagnostic and screening procedures, and finally evaluating the impact of lung-heart comorbidities on the therapeutic management of patients with COPD and heart diseases.

Impact of individualized care on readmissions after a hospitalization for acute exacerbation of COPD.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) increase COPD morbidity and mortality and impose a great burden on health care systems. Early readmission following a hospitalization for AECOPD remains an important clinical problem. We examined how individualized comprehensive care influences readmissions following an index hospital admission for AECOPD. METHODS: We retrospectively reviewed data of patients admitted for AECOPD to two inner-city teaching hospitals to determine the impact of a comprehensive and individualized care management strategy on readmissions for AECOPD. The control group consisted of 271 patients whose index AECOPD occurred the year before the comprehensive program, and the experimental group consisted of 191 patients who received the comprehensive care. The primary outcome measure was the total number of readmissions in 30- and 90-day postindex hospitalizations. Secondary outcome measures included the length of time between the index admission and first readmission and all-cause mortality. RESULTS: The two groups were similar in terms of age, sex, forced expiratory volume in 1 second, body mass index (BMI), pack-years, and the number and types of comorbidities. Comprehensive care significantly reduced 90-day readmission rates in females (P=0.0205, corrected for age, BMI, number of comorbidities, substance abuse, and mental illness) but not in males or in the whole group (P>0.05). The average times between index admission and first readmission were not different between the two groups. Post hoc multivariate analysis showed that substance abuse (P<0.01) increased 30- and 90-day readmissions (corrected for age, sex, BMI, number of comorbidities, and mental illness). The 90-day all-cause in-hospital mortality rates were significantly less in the care package group (2.67% versus 7.97%, P=0.0268). CONCLUSION: Comprehensive individualized care for subjects admitted to hospital for AECOPD did not reduce 30- and 90-day readmission rates but did reduce 90-day total mortality. Interestingly, it reduced 90-day readmission rate in females. We speculate that an individualized care package could impact COPD morbidity and mortality after an acute exacerbation.

Impact of cardioselective beta-blockers on mortality in patients with chronic obstructive pulmonary disease and atherosclerosis.

RATIONALE: beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms. OBJECTIVES: We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery. METHODS: We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose. MEASUREMENTS AND MAIN RESULTS: There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not. CONCLUSIONS: Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.