Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

The effect of problem-based learning in patient education after an event of CORONARY heart disease - a randomised study in PRIMARY health care : design and methodology of the COR-PRIM study

Background Even though there is convincing evidence that self-care, such as regular exercise         and/or stopping smoking, alters the outcomes after an event of coronary heart disease         (CHD), risk factors remain. Outcomes can improve if core components of secondary prevention         programmes are structurally and pedagogically applied using adult learning principles         e.g. problem-based learning (PBL). Until now, most education programs for patients         with CHD have not been based on such principles. The basic aim is to discover whether         PBL provided in primary health care (PHC) has long-term effects on empowerment and         self-care after an event of CHD.      Methods/Design A randomised controlled study is planned for patients with CHD. The primary outcome         is empowerment to reach self-care goals. Data collection will be performed at baseline         at hospital and after one, three and five years in PHC using quantitative and qualitative         methodologies involving questionnaires, medical assessments, interviews, diaries and         observations. Randomisation of 165 patients will take place when they are stable in         their cardiac condition and have optimised cardiac medication that has not substantially         changed during the last month. All patients will receive conventional care from their         general practitioner and other care providers. The intervention consists of a patient         education program in PHC by trained district nurses (tutors) who will apply PBL to         groups of 6–9 patients meeting on 13 occasions for two hours over one year. Patients         in the control group will not attend a PBL group but will receive home-sent patient         information on 11 occasions during the year.      Discussion We expect that the 1-year PBL-patient education will improve patients’ beliefs, self-efficacy         and empowerment to achieve self-care goals significantly more than one year of standardised         home-sent patient information. The assumption is that PBL will reduce cardiovascular         events in the long-term and will also be cost-effective compared to controls. Further,         the knowledge obtained from this study may contribute to improving patients’ ability         to handle self-care, and furthermore, may reduce the number of patients having subsequent         CHD events in Sweden.COR-PRIM stud

The effect of problem-based learning in patient education after an event of CORONARY heart disease - a randomised study in PRIMARY health care : design and methodology of the COR-PRIM study

Background Even though there is convincing evidence that self-care, such as regular exercise         and/or stopping smoking, alters the outcomes after an event of coronary heart disease         (CHD), risk factors remain. Outcomes can improve if core components of secondary prevention         programmes are structurally and pedagogically applied using adult learning principles         e.g. problem-based learning (PBL). Until now, most education programs for patients         with CHD have not been based on such principles. The basic aim is to discover whether         PBL provided in primary health care (PHC) has long-term effects on empowerment and         self-care after an event of CHD.      Methods/Design A randomised controlled study is planned for patients with CHD. The primary outcome         is empowerment to reach self-care goals. Data collection will be performed at baseline         at hospital and after one, three and five years in PHC using quantitative and qualitative         methodologies involving questionnaires, medical assessments, interviews, diaries and         observations. Randomisation of 165 patients will take place when they are stable in         their cardiac condition and have optimised cardiac medication that has not substantially         changed during the last month. All patients will receive conventional care from their         general practitioner and other care providers. The intervention consists of a patient         education program in PHC by trained district nurses (tutors) who will apply PBL to         groups of 6–9 patients meeting on 13 occasions for two hours over one year. Patients         in the control group will not attend a PBL group but will receive home-sent patient         information on 11 occasions during the year.      Discussion We expect that the 1-year PBL-patient education will improve patients’ beliefs, self-efficacy         and empowerment to achieve self-care goals significantly more than one year of standardised         home-sent patient information. The assumption is that PBL will reduce cardiovascular         events in the long-term and will also be cost-effective compared to controls. Further,         the knowledge obtained from this study may contribute to improving patients’ ability         to handle self-care, and furthermore, may reduce the number of patients having subsequent         CHD events in Sweden.COR-PRIM stud

Association Between Experimental Pain Thresholds and Trajectories of Postoperative Recovery Measures After Benign Hysterectomy

PURPOSE: Quantitative sensory testing (QST) can be applied to quantify the sensitivity to different painful stimuli. This study aims to evaluate the association between preoperative pressure and thermal pain thresholds and trajectories of measurements of postoperative recovery (patient-reported daily maximum and average pain intensity, sum score of symptoms, and analgesic consumption) after benign hysterectomy. PATIENTS AND METHODS: A prospective, longitudinal single-blinded, observational multicenter study was conducted in five hospitals in the southeast of Sweden between 2011 and 2017. A total of 406 women scheduled for abdominal or vaginal hysterectomy for benign conditions were enrolled in the study. QST measuring pressure (PPT), heat (HPT), and cold pain thresholds (CPT) were performed preoperatively. The cut-off levels for dichotomizing the pain thresholds (low/high) were set at the 25-percentile for PPT and HPT and the 75-percentile for CPT. The Swedish Postoperative Symptom Questionnaire was used to measure postoperative pain and other symptoms of discomfort (symptom sum score) on 13 occasions for six weeks postoperatively. Daily analgesic consumption of opioids and non-opioids was registered. RESULTS: A CPT above the 75-percentile was associated with high postoperative maximum pain intensity (p = 0.04), high symptom sum score (p = 0.03) and greater consumption of non-opioids (p = 0.03). A HPT below the 25-percentile was only associated with greater consumption of non-opioids (p = 0.02). PPT was not associated with any of the outcome measures. CONCLUSION: CPT seemed to be predictive for postoperative pain and symptoms of discomfort after benign hysterectomy. Preoperative QST may be used to individualize the management of postoperative recovery for low pain threshold individuals

The effect of problem-based learning in patient education after an event of CORONARY heart disease – a randomised study in PRIMARY health care: design and methodology of the COR-PRIM study

Abstract Background Even though there is convincing evidence that self-care, such as regular exercise and/or stopping smoking, alters the outcomes after an event of coronary heart disease (CHD), risk factors remain. Outcomes can improve if core components of secondary prevention programmes are structurally and pedagogically applied using adult learning principles e.g. problem-based learning (PBL). Until now, most education programs for patients with CHD have not been based on such principles. The basic aim is to discover whether PBL provided in primary health care (PHC) has long-term effects on empowerment and self-care after an event of CHD. Methods/Design A randomised controlled study is planned for patients with CHD. The primary outcome is empowerment to reach self-care goals. Data collection will be performed at baseline at hospital and after one, three and five years in PHC using quantitative and qualitative methodologies involving questionnaires, medical assessments, interviews, diaries and observations. Randomisation of 165 patients will take place when they are stable in their cardiac condition and have optimised cardiac medication that has not substantially changed during the last month. All patients will receive conventional care from their general practitioner and other care providers. The intervention consists of a patient education program in PHC by trained district nurses (tutors) who will apply PBL to groups of 6–9 patients meeting on 13 occasions for two hours over one year. Patients in the control group will not attend a PBL group but will receive home-sent patient information on 11 occasions during the year. Discussion We expect that the 1-year PBL-patient education will improve patients’ beliefs, self-efficacy and empowerment to achieve self-care goals significantly more than one year of standardised home-sent patient information. The assumption is that PBL will reduce cardiovascular events in the long-term and will also be cost-effective compared to controls. Further, the knowledge obtained from this study may contribute to improving patients’ ability to handle self-care, and furthermore, may reduce the number of patients having subsequent CHD events in Sweden. Trial registration NCT01462799</p

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)