A Multicenter, Randomized, Placebo-Controlled Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients With Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P 50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety. RESULTS: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient‐years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low‐density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C‐reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI −14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar. CONCLUSION: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations

Osteomyelitis and Fracture Susceptibility: A Review of the Literature and Case Series of Surgical Treatment of Pathologic Calcaneal Fractures

Introduction: Pathologic calcaneal fractures, often arising from osteomyelitis, present intricate challenges in orthopedic surgery. This paper explores the historical context, etiological factors, and evolving treatment approaches for these fractures, with a focus on the interplay between infection and compromised bone integrity. Methods: A retrospective analysis of four cases of pathologic calcaneal fractures complicating osteomyelitis, treated at the University of Pittsburgh Medical Center from 2017 to 2021, was conducted. The patients underwent debridement, external fixation, and long-term antibiotic therapy. A comprehensive literature review was conducted, encompassing all relevant papers discussing surgical treatment strategies for pathologic calcaneal fractures. Results: The case series reveals the complexities of managing these fractures. While external fixation stabilized the fractures and facilitated infection control, the outcomes varied. Some patients achieved fracture union and improved ulceration, while others experienced complications and, tragically, mortality due to underlying comorbidities. Discussion: Treatment modalities for osteomyelitis-related calcaneal fractures encompass debridement, external fixation, and tailored antibiotic therapy. Debridement is essential for infection control and wound preparation. External fixation provides stability, facilitates wound care, and allows for antibiotic delivery. Antibiotic therapy complements surgical interventions and targets the infection. However, challenges persist, including compromised overall health, persistent infection, and limited long-term outcomes. Conclusion: Pathologic calcaneal fractures complicated by osteomyelitis pose a formidable clinical challenge. Despite innovative approaches like the use of suture anchors and external fixation, achieving successful outcomes remains elusive. These cases often result in substantial morbidity and, at times, mortality due to the intricate interplay of infection, compromised bone quality, and comorbidities. Clinicians must balance aggressive intervention with a realistic assessment of the patient's overall health and prognosis. Further research and standardized treatment approaches are imperative to address the unique complexities of these cases and improve patient outcomes