Statin intolerance in a referral lipid clinic.

BACKGROUND: Statins effectively prevent atherosclerotic cardiovascular disease, but rates of statin discontinuation after adverse events are high. OBJECTIVE: Describe the range and relative frequencies of adverse events potentially attributable to statins in lipid referral practice and assess statin rechallenge outcomes. METHODS: Retrospective cohort study of 642 patients with statin-associated adverse events evaluated in a referral lipid clinic between January 1, 2004 and January 27, 2011. RESULTS: Patients experiencing adverse events by organ system included 92% with musculoskeletal, 8% central nervous system, 10% liver, 8% gastrointestinal, 5% peripheral nervous system, 5% skin, and 3% other events. Overlap of organ system involvement occurred in 22.5%. At least 1 follow-up visit was made by 557 patients, among whom overall median follow-up was 25 months. Among patients treated with a statin in the clinic, 71% remained on a statin at the last follow-up visit. Patients with hepatic transaminase increases by history were numerically more likely than the overall group to resume or remain on statin treatment, whereas those reporting central nervous system or gastrointestinal symptoms trended lower for statin maintenance. Among patients who experienced an adverse event after statin rechallenge, the majority (64%) were being treated with intermittent, nondaily dosing at the time of the adverse event. CONCLUSION: Although musculoskeletal symptoms are reported by 90% of patients with statin intolerance, symptoms involving other organ systems may be more frequent than previously supposed. Understanding the range of symptoms, time course, and impact on daily activities informs counseling in patient-centered practice, but assessment of causation by statins remains challenging.

Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short?

The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention.

Statin intolerance: more questions than answers.

The dramatic effectiveness of statins in improving the course of atherosclerotic cardiovascular disease tends to overshadow questions of statin intolerance. Thus after more than 25 years of clinical statin use, intolerance remains a poorly understood, frustrating issue for patients and providers. It has been extraordinarily difficult to define statin intolerance and its implications for clinical practice. Here, we briefly summarize current knowledge and raise questions that need to be addressed.

Adverse reactions of Achilles tendon xanthomas in three hypercholesterolemic patients after treatment intensification with niacin and bile acid sequestrants.

Multiple cholesterol-reducing therapies have been shown to induce the regression of tendon xanthoma in patients with familial hypercholesterolemia. We present 3 cases of adverse reactions in Achilles tendon xanthomas after the addition of niacin and bile acid sequestrants to ongoing statin therapy. Reduction in tendon dimensions and marked softening of xanthomas were interpreted as cholesterol removal from heavily infiltrated tissue sites. In 2 cases, changes in the xanthomas occurred despite only minor lipoprotein improvements, raising the possibility of direct drug effects in cholesterol-infiltrated tissue. Intriguingly, recent studies have described niacin receptor-mediated effects in macrophages. In summary, although adverse reactions in Achilles tendon xanthomas appear to be infrequent, clinicians should be aware of this phenomenon in their patients after intensifying lipid treatments, especially with the use of niacin in patients with familial hypercholesterolemia. Xanthoma responses may provide clues to new pharmacologic effects in cholesterol-infiltrated tissues.

Osteoporosis in lung transplant candidates compared to matched healthy controls.

PURPOSE: Advanced lung disease increases the risk for diminished bone mineral density (BMD). The prevalence and severity of osteoporosis in lung transplant candidates is unclear. METHODS: We retrospectively evaluated BMD of subjects screened for lung transplant at our institution. Observed prevalence of osteoporosis and osteopenia within our cohort was compared to the expected prevalence of each from the Third National Health and Nutrition Examination Survey (NHANES III) data matched for age, gender, and race. Lateral chest radiographs were evaluated for vertebral fractures. RESULTS: High prevalence rates of osteoporosis (37%) and combined osteoporosis/osteopenia (86%) were observed. Subjects with pulmonary fibrosis had higher BMD and T-scores compared to all other subgroups. All subjects within the cohort had a higher observed combined rate of osteoporosis/osteopenia at all bone sites compared to expected rates from healthy, matched controls. Vertebral fractures were present in 23% of subjects but did not correlate with BMD or the diagnosis of osteoporosis. CONCLUSIONS: Abnormal BMD was prevalent in most pre-lung transplant subjects, with striking differences noted in comparison with a healthy, matched cohort. Lateral chest radiographs in combination with BMD data give a more complete picture of bone abnormalities. Osteoporosis screening prior to lung transplantation should be performed to identify high-risk subjects for fracture and allow for intervention.