Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A current and future outlook on upcoming technologies in the remote monitoring of patients with heart failure

Heart failure is a major health and economic challenge in both developing and developed countries. Despite advances in pharmacological and device therapies for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure (HFrEF), their quality of life (QoL) and exercise capacity are often persistently impaired, morbidity and mortality remain high and the health economic and societal costs are considerable. For patients with heart failure and preserved LVEF (HFpEF), diuretic management has an essential role for controlling congestion and symptoms even if no intervention has been convincingly shown to reduce morbidity or mortality. Remote monitoring might improve care delivery and clinical outcomes for patients regardless of LVEF. A great variety of innovative remote monitoring technologies and algorithms are being introduced, including patient self‐managed testing, wearable either as integrated into established clinically indicated therapeutic devices, such as pacemakers and defibrillators, or as stand‐alone are in development providing the promise of further improvements in service delivery and clinical outcomes. In this article, we will discuss unmet needs in the management of patients with HF, how remote monitoring might contribute to future solutions and provide an overview of current and novel remote monitoring technologies

Sarcopenia in patients with heart failure with preserved ejection fraction: Impact on muscle strength, exercise capacity and quality of life

Background To describe the prevalence of sarcopenia in ambulatory patients with heart failure with preserved ejection fraction (HFpEF) and its relation to reduced exercise capacity, muscle strength, and quality of life (QoL). Methods and results A total of 117 symptomatic outpatients with HFpEF were prospectively enrolled in Germany, England, and Slovenia as part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Appendicular skeletal muscle (ASM) mass (the sum of muscle mass in both arms and legs) was assessed by DEXA. Echocardiography, 6-minute walk testing (6-MWT), muscle strength assessment, spiroergometry and QoL evaluation using EQ-5D Questionnaire were performed. Sarcopenia was defined as ASM 2 standard deviations below the mean of a healthy reference group aged 18–40 years. Patients were divided into 3 groups according to the E/e′ value: ≤ 8, 9–14, and ≥ 15. Sarcopenia was detected in 19.7% of all patients. These patients performed worse during 6-MWT (404 ± 116 vs. 307 ± 145 m, p = 0.003) and showed lower absolute peak oxygen consumption (1579 ± 474 vs. 1211 ± 442 mL/min, p 15 (p < 0.05). Higher values of muscle strength/ASM were associated with a better QoL (r = 0.5, p < 0.0005). Logistic regression showed ASM to be independently associated with reduced distance walked during the 6-MWT adjusted for NYHA, height, left atrium diameter, ferritin and forced expiratory volume in 1 s (FEV1) (odds ratio 1.2, p = 0.02). Conclusion Sarcopenia affects a clinically relevant proportion of patients with HFpEF. Low ASM is strongly linked to reduced muscle strength, exercise capacity and QoL in these patients

Exercise benefits in cardiovascular disease : beyond attenuation of traditional risk factors

Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health