Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing

Background: Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise-induced ventricular arrhythmias has not been investigated.
Methods and Results: We evaluated the association between statin use and PVCs in 1,847 heart-failure-free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity-adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37–0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30–0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise-induced angina, or exercise capacity.
Conclusions: Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.     

Prevalence of Musculoskeletal Pain and Statin Use

Background  Muscle effects are the most common reported adverse effects of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins). However, in placebo-controlled trials the incidence of muscle pain is most often similar for placebo and active control groups. Objective  We sought to evaluate whether statin use was associated with a higher prevalence of musculoskeletal pain in a nationally representative sample. Methods  Cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Participants were 3,580 adults ≥40 years without arthritis who were interviewed at home and examined in a mobile examination center. Participants were asked about sociodemographic characteristics, health conditions, medication use, and musculoskeletal pain. Height, weight, blood pressure, ankle brachial index, and cholesterol were measured. Measurements and Main Results  Prevalence and adjusted odds ratios (OR) of any musculoskeletal pain and musculoskeletal pain in 4 different anatomical regions (neck/upper back, upper extremities, lower back, and lower extremities) by statin use during the last 30 days. Among statin users (n = 402), 22.0% (95%CI 18.0–26.7%) reported musculoskeletal pain in at least 1 anatomical region during the last 30 days, compared with 16.7% (95%CI 15.1–18.4%) of those who did not use a statin. Compared to persons who did not use statins, those who used statins had multivariable-adjusted odds ratios (95%CI; p value) of 1.50 (1.07–2.11; p = .01) for any musculoskeletal pain, 1.59 (1.04–2.44, p = .03) for lower back pain, and1.50 (1.02–2.22, p = .03) for lower extremity pain. Conclusion  Musculoskeletal pain is common in adults ≥40 years without arthritis. In this nationally representative sample, statin users were significantly more likely to report musculoskeletal pain.     

Non-low-density lipoprotein cholesterol-associated actions of ezetimibe: an overview

Ezetimibe, an intestinal cholesterol absorption inhibitor, lowers circulating low-density lipoprotein cholesterol (LDL-C) levels both when administered as monotherapy and in combination with other hypolipidaemic drugs, mostly statins. This review focuses on the effects of ezetimibe on non-LDL-C-associated variables. In most studies, ezetimibe effectively reduced triglyceride and increased high density lipoprotein cholesterol levels. The authors also consider the effect of ezetimibe on other variables such as C-reactive protein levels, insulin sensitivity and endothelial function. Ezetimibe is useful in patients with sitosterolaemia (a rare inherited disorder) as it significantly reduces plasma phytosterol concentrations. Ezetimibe fulfils two of the three essential characteristics of any drug (efficacy and safety). However, clinical studies are required to provide evidence of its ability to reduce vascular events.     

The controversy of a wider statin utilization: why?

Introduction: Several medical journals published viewpoints and counter-viewpoints supporting or opposing a wider utilization of statins for primary prevention. The objective of this article is not to weigh in the benefits versus risks of statin use, but to discuss various aspects of this controversy.

Areas covered: This review discusses the challenges in examining the pleotropic effects/adverse events of statins. It also discusses the pitfalls in assessment of adverse events in randomized controlled trials and observational studies.

Expert opinion: The challenges in solving this controversy include that the pleotropic effect of statins results in an extremely wide spectrum of reported benefits or adverse events, the reported harms/benefits are contradictory, there is basic research ground supporting both sides of the controversy, it is difficult to separate if adverse events are due to statins or due to lower cholesterol, and that there is a lack of standardized definition of statin-associated adverse events and their methods of ascertainment. Both randomized controlled trials and observational studies have pitfalls and caveats in assessment of adverse events. Understanding the points of debate is of paramount significance to enable clinicians to individualize patient care.     

Challenges in the management of asthma associated with smoking-induced airway diseases

ABSTRACT

Introduction: Smoking-induced airway diseases such as chronic bronchitis, emphysema, and small airway dysfunction contribute to the chronic respiratory symptoms experienced by adults with asthma, including those with spirometric chronic obstructive pulmonary disease (COPD), termed asthma-COPD overlap (ACO). Drug treatment of symptomatic smokers with asthma or ACO is uncertain due to their exclusion from most clinical trials.

Areas covered: This review summarizes evidence for the efficacy of small molecule drugs used in the clinic to treat current and former smokers with a diagnostic label of asthma or ACO. Other therapeutic interventions are reviewed, including smoking cessation and biologics.

Expert opinion: Clinical trials and observational studies suggest that smoking cessation and approved drugs used to treat non-smokers with asthma produce clinical benefits in smokers with asthma or ACO, although the overall quality of evidence is low. The efficacy of some treatments for asthma is altered in current smokers, including reduced responsiveness to short-term inhaled corticosteroids and possibly improved responsiveness to leukotriene receptor antagonists. Preliminary findings suggest that low-dose theophylline, statins, and biologics, such as omalizumab, mepolizumab, and dupilumab, may improve clinical outcomes in smokers with asthma or ACO. Improved phenotyping and endotyping of asthma and smoking-induced airway diseases should lead to better targeted therapies.     

Lipid-lowering effects of statins: a comparative review

The pharmacological regulation of lipid metabolism in patients with dyslipidaemia is unequivocally associated with significant reductions in risk for cardiovascular morbidity and mortality. There is strong clinical trial data to support of the use of statin therapies in the settings of both primary and secondary prevention. This paper addresses: i) the mechanisms of action of antilipidaemic medications; ii) dosing regimens and the pharmacokinetic differences among drugs of the same class; iii) risk for drug interactions; and iv) reviews the clinical trial evidence used to support the use of particular antilipidaemic medications in specific physiological settings.     

Current role of statins in the treatment of essential hypertension

Importance of the field: Hypertension and hyperlipidemia often co-exist and seem to be interrelated through common pathophysiological pathways. Drugs employing beneficial effects in both conditions could be advantageous in a concerted effective management of patients at high cardiovascular risk. Statins are known to enhance cardiovascular protection beyond their lipid-lowering capacity.

Areas covered in this review: MEDLINE was searched, up to January 2010, for studies assessing the effect of statin treatment on blood pressure control in various populations or animal models of hypertension. The potential mechanisms implicated in the putative antihypertensive action of statins are also reviewed.

What the reader will gain: To learn about the role of statins as potential antihypertensive drugs in various populations. Clinical advice for the use of statins either as monotherapy or in combination with antihypertensive drugs in high-risk populations is also provided.

Take home message: Statins may exert a mild, but clinically relevant, antihypertensive effect which is probably mediated by mechanisms that are independent of their lipid-lowering effects. Patients with high BP levels at baseline as well as those treated with ACE inhibitors and calcium channel blockers are expected to benefit more in this regard.     

Statins and stroke prevention

Over the past decade, statins have been proved to significantly decrease coronary events in the primary and secondary prevention of coronary artery disease. Recent clinical trials have indicated that statins significantly reduce stroke risk in patients with vascular disease. A meta-analysis of randomized trials of statins in combination with other preventive strategies, involving 165,792 individuals, showed that each 1-mmol/l (39 mg/dl) decrease in LDL-cholesterol equates to a reduction in relative risk for stroke of 21.1 (95% CI: 6.3–33.5; p = 0.009). It is not known whether these findings might be due to the cholesterol-reduction effect of statins or to the pleiotropic effects of statins, such as improved endothelial function, decreased platelet aggregability and reduced vascular inflammation. In the secondary prevention of stroke, The Stroke Prevention by Aggressive Reduction of Cholesterol Levels study found that treatment with atorvastatin reduced the risk of recurrent cerebrovascular events in patients with recent stroke or transient ischemic attack but no history of heart disease.