Guideline-directed medical therapy for secondary prevention after coronary artery bypass grafting in patients with depression

AbstractBackgroundWe hypothesized that depressed patients would have lower use of guideline-directed medical therapy for secondary prevention of cardiovascular events following coronary artery bypass grafting (CABG).MethodsWe included all patients who underwent primary isolated CABG in Sweden between 2006 and 2008. We cross-linked individual level data from national Swedish registers. Preoperative depression was defined as at least one antidepressant prescription dispensed before surgery. We defined medication use as at least two dispensed prescriptions in each medication class (antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), and statins) within a rolling 12 month period. We calculated adjusted risk ratios (RR) for the use of each medication class, and for all four classes, after one and four years, respectively.ResultsDuring the first year after CABG, 93% of all patients (n = 10,586) had at least two dispensed prescriptions for an antiplatelet agent, 68% for an ACEI/ARB, 91% for a beta-blocker, and 92% for a statin. 57% had prescriptions for all four medication classes. After four years (n = 4034), 44% had filled prescriptions for all four medication classes. Preoperative depression was not significantly associated with a lower use of all four medication classes after one year (RR 0.98, 95% confidence interval (CI) 0.93–1.03) or after four years (RR 0.97, 95% CI 0.86–1.09).ConclusionsPreoperative depression was not associated with lower use of guideline-directed medical therapy for secondary prevention after CABG. These findings suggest that the observed higher mortality following CABG among depressed patients is not explained by inadequate secondary prevention medication

Cardiovascular risk assessments in peripheral arterial disease : results of a ten-year follow-up of a Swedish population-based cohort

Background An updated knowledge on natural history in Peripheral Arterial Disease (PAD) is lacking, in particular for the asymptomatic stage (APAD). The disease has strong associations with other atherosclerotic manifestations such as myocardial infarction or stroke, which could be prevented with prophylactic measures. PAD is easily detected through simple ankle and brachial blood pressure measurements, why screening for this condition has been suggested but is yet not proven cost-effective. Identification of PAD could be useful in cardiovascular (CV) risk assessments. To improve health in society and to reduce costs for care, improved prophylactic strategies is needed in CV management. Before that, improved knowledge of the natural history of PAD is essential. This project describes mortality, CV outcome and treatment patterns in symptomatic and asymptomatic PAD men and women. Methods and Results Study I A population sample of 5080 subjects, selected through randomization, was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was compared with the PAD stage determined at baseline in 2005. The age-adjusted hazard ratios for a main cause of death by a CV event were 1.9 [95% CI 1.5-2.3] in Asymptomatic PAD, 2.6 [95% CI 2.1-3.4] in Intermittent Claudication, and 3.5 [95% CI 2.3-5.2] in Severe Limb Ischemia stage groups. Study II This was a prospective observational population-based cohort study based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ABI levels and reported symptoms as in study I. After adjustments for age, comorbidity, and sex, the risk was almost doubled for CV death in Intermittent Claudication and APAD subjects (HR 1.95 and 1.80) as compared to a reference population. The risk for other comorbidity as diabetes, non-fatal myocardial infarction and stoke and renal failure was doubled in PAD. Some 60% of symptomatic PAD subjects received the pharmacological prophylactic treatment as recommended in guidelines. Study III This study evaluated the risks for adverse CV events in subjects with APAD in combination with different known traditional CV risk factors over a ten-year observation period. For subjects with hypertension at baseline the CV mortality incidence was 35.4 deaths per 1000 person-years when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p<0.001]. Study IV This prospective study assessed the differences in CV outcome if using the highest (ABI-HI) or lowest (ABI-LO) ankle blood pressure for ABI calculation for PAD diagnosis in a population-based cohort. The prevalence of PAD, defined by an ABI<0.9, by using ABI-LO and ABI-HI was 16.3% (n=799) and 9.6 % (n=469), respectively. For the subgroups defined by ABI-LO and ABI-HI, the age-adjusted HR [95% CI] for the composite outcome CV mortality and non-fatal CV events, was 1.25 [1.06-1.49] and 2.11 [1.85-2.39] respectively. The predictive value of an ABI<0.9 to foresee a future event was low for both calculation methods. Conclusions The mortality is more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. The prognosis for this group has not changed over the last decades in contrary to other CV manifestations. Among all PAD subjects, CV causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. APAD subjects confer almost similar risk for CV events as symptomatic patients. PAD is more common in women, but men face a higher risk for death and CV events. Some 60% of symptomatic PAD subjects received prophylactic drugs according to guidelines by 2015. Subjects with APAD and any other CV risk factor have significantly higher risks for CV events and could therefore constitute suitable populations for further studies of screening with ABI measurements and subsequent intensified CV prophylactic treatment. When using the ABI-LO method more subjects at risk were identified, but their average risk was lower when comparing to the ABI-HI method which identified less subjects at risk. These differences are important to be aware of in further studies of screening. ABI measurements should be considered an important indication in aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor

Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum.

AIMS: We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40-49%]. METHODS AND RESULTS: In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow-up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient-years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient-years in HFrEF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75-0.91; P < 0.001], 7.4 vs. 9.7 per 100 patient-years in HFmrEF (HR 0.76, 95% CI 0.61-0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient-years in HFpEF (HR 0.95, 95% CI 0.79-1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58-0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33-0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59-1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%. CONCLUSION: Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF. ClinicalTrials.gov: CHARM Alternative NCT00634400, CHARM Added NCT00634309, CHARM Preserved NCT00634712

Data from a pooled post hoc analysis of 14 placebo-controlled, dapagliflozin treatment studies in patients with type 2 diabetes with and without anemia at baseline

Dapagliflozin is a highly selective sodium-glucose cotransporter 2 inhibitor associated with stabilization of estimated glomerular filtration rate (eGFR); reductions in glycated hemoglobin (HbA1c), systolic blood pressure, body weight, and albuminuria; and a small and consistent increase in hematocrit [1], [2], [3], [4]. This data set is based on the associated article [5] analyzing data from 5325 patients with type 2 diabetes from 14 placebo-controlled, phase 3 (one phase 2/3), double-blind dapagliflozin treatment studies of 24-104 weeks' duration. Data on dapagliflozin's effects (vs. placebo) on hemoglobin (Hb), hematocrit, serum albumin, serum total protein concentrations, urine albumin/creatinine ratio, eGFR, heart rate, blood pressure, body weight, and safety in patients with type 2 diabetes with and without anemia were pooled and analyzed. Patients were divided into two groups according to baseline Hb levels: anemia (Hb 16.5 g/dL in men and >16.0 g/dL in women). Because anemia commonly occurs in patients with diabetes and chronic kidney disease [6], the data can be of value to further analyze trends in relevant physiological and pathophysiological parameters

Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study

Aims: Dapagliflozin is a selective inhibitor of sodium glucose co-transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45-59mL/min/1.73m2; chronic kidney disease [CKD] stage 3A). Materials and methods: In this double-blind, parallel group, Phase 3 study (NCT02413398, clinicaltrials.gov) patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N=160) or matching placebo (N=161) for 24weeks. Randomization was stratified by pre-enrolment glucose-lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24. Results: At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], -0.34% [-0.53, -0.15]; P < 0.001), body weight (difference [95% CI], -1.25kg [-1.90, -0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], -0.9 mmol/L [-1.5, -0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], -3.1 mmHg [-6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (-2.49mL/min/1.73m2[-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61mL/min/1.73m2[-1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported. Conclusions: The findings of this study (NCT02413398, clinicaltrials.gov) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers

The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was -71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined

Correction of anemia by dapagliflozin in patients with type 2 diabetes

Aims: Anemia is common in type 2 diabetes (T2D), particularly in patients with kidney impairment, and often goes unrecognized. Dapagliflozin treatment increases hemoglobin and serum erythropoietin levels. We investigated the effect of dapagliflozin 10-mg/day on hemoglobin in T2D patients with and without anemia. Methods: Data from 5325 patients from 14 placebo-controlled, dapagliflozin-treatment studies of at least 24-weeks duration were pooled. Dapagliflozin's effects (vs. placebo) on hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), systolic blood pressure, body weight, and safety in patients with and without anemia were evaluated. Results: At baseline, 13% of all T2D patients and 28% of those with chronic kidney disease (eGFR Conclusions: Treatment with dapagliflozin can correct and prevent anemia in T2D patients. A gradual increase in hemoglobin beyond week 4 may indicate an erythropoiesis-stimulating effect of sodium-glucose cotransporter 2 inhibition. (c) 2020 Published by Elsevier Inc

Continuous surgical multi-level extrapleural block for video-assisted thoracoscopic surgery: a retrospective study assessing its efficacy as pain relief following lobectomy and wedge resection [version 1; peer review: 2 approved]

Background: Video-assisted thoracoscopic surgery (VATS) causes less postoperative pain than thoracotomy; however, adequate analgesia remains vital. As part of a multi-modal postoperative analgesia, a continuous surgeon-placed extrapleural block catheter is an option. The aim of this retrospective study was to evaluate the analgesic efficacy of a continuous extrapleural block as part of a multimodal analgesic regimen after VATS in general, and VATS lobectomy and wedge resection in particular. Methods: Case records for patients having undergone VATS surgery and been provided a multi-level continuous extrapleural block with an elastomeric pump infusing levobupivacaine 2.7 mg/ml at a rate of 5 ml/h during 2015 and 2016 were reviewed. Pain (Numeric Rating Scale) at rest and mobilisation as well as opioid requirement (daily, postoperative days 0-3, as well as accumulated) were analysed.    Results: In all, 454 records were reviewed: 150 wedge resections, 264 lobectomies and 40 miscellaneous cases. At rest, pain was mild median NRS rated 3-3-1-1 for postoperative day (POD) 0 to 3, during movement, pain was rated moderate during POD 0 and 1 and mild the remaining days (median NRS 4-4-3-3 for POD 0-3). The proportion of patients exhibiting mild pain at rest increased from 55% on POD 0 to 81 % on POD 3. The percentage of patients experiencing severe pain at rest decreased from 15% to 6%. Median oxycodone consumption was 10 mg per day for POD 1-3. Pain after VATS wedge resection was significantly lower at POD 1 and 3 compared to pain after VATS lobectomy. Conclusion: We found a continuous surgeon-placed extrapleural catheter block to be a valuable and seemingly safe addition to our multimodal procedure specific analgesia after VATS. Whether the efficacy of the block can be improved by increasing local anaesthetic and/or adding adjuncts warrants further investigation