2011 August 08

Managing the underestimated risk of statin-associated myopathy.

Aug 082011

Managing the underestimated risk of statin-associated myopathy.

Int J Cardiol. 2011 Aug 1;

Authors: Rallidis LS, Fountoulaki K, Anastasiou-Nana M

In clinical practice 5-10% of patients receiving statins develop myopathy, a side effect that had been systematically underestimated in the randomized controlled trials with statins. The most common manifestation of myopathy is muscle pain (usually symmetrical, involving proximal muscles) without creatinine kinase (CK) elevation or less frequently with mild CK elevation. Clinically significant rhabdomyolysis (muscle symptoms with CK elevation >10 times the upper limit of normal and with creatinine elevation) is extremely rare. Myopathy complicates the use of all statins (class effect) and is dose-dependent. The pathophysiologic mechanism of statin-associated myopathy is unknown and probably multifactorial. The risk of statin-associated myopathy can be minimized by identifying vulnerable patients (i.e. patients with impaired renal or liver function, advanced age, hypothyroidism, etc.) and/or by eliminating-avoiding statin interactions with specific drugs (cytochrome P-450 3A4 inhibitors, gemfibrozil, etc.). In symptomatic patients, the severity of symptoms, the magnitude of CK elevation and the risk/benefit ratio of statin continuation should be considered before statin treatment is discontinued. Potential strategies are the use of the same statin at a lower dose and if symptoms recur the initiation of fluvastatin XL 80mg daily or rosuvastatin intermittently in low dose (5-10mg), combined usually with ezetimibe 10mg daily. Failure of these approaches necessitates the use of non-statin lipid lowering drugs (ezetimibe, colesevelam). In order to provide evidence based recommendations for the appropriate management of statin-intolerant patients we need randomized clinical trials directly comparing the myopathic potential of different lipid-lowering medications at comparable doses.

PMID: 21813193 [PubMed - as supplied by publisher]

Link to Article at PubMed

Early onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis.

Am J Respir Crit Care Med Start a Discussion »

Aug 082011

Early onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis.

Am J Respir Crit Care Med. 2011 Aug 4;

Authors: Perbet S, Mongardon N, Dumas F, Bruel C, Lemiale V, Mourvillier B, Carli P, Varenne O, Mira JP, Wolff M, Cariou A

RATIONALE: Even if frequent, little is known concerning early onset pneumonia that occurs in the post-resuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, its influence on the occurrence of early onset pneumonia is not well defined. OBJECTIVES: To describe the incidence, risk factors, causative agents, and impact on outcome of early onset pneumonia occurring within 3 days after out-of-hospital cardiac arrest (OHCA). METHODS: Retrospective analysis of a large cohort study of all patients successfully resuscitated after OHCA and admitted from July 2002 to March 2008 in two medical ICUs. Patients who presented accidental hypothermia or a known pneumonia prior to OHCA, or patients who died within the first 24 hours were excluded. MEASUREMENTS AND MAIN RESULTS: During this 6-year period, 845 patients were admitted after OHCA, and 641 consecutive patients were included. Five hundred patients (78%) were treated with therapeutic hypothermia. In the first 3 days, 419 (65%) presented early onset pneumonia. Multivariate analysis disclosed therapeutic hypothermia as the single independent risk factor of early onset pneumonia (OR 1.90; 95%CI 1.28-2.80, p=0.001). ). Early onset pneumonia increased length of mechanical ventilation (5.7±5.9 vs.4.7±6.2 days; p=0.001) and ICU stay (7.9±7.2 vs. 6.7±7.6 days; p=0.001), but did not influence incidence of ventilator-associated pneumonia (p=0.25), favorable neurologic outcome (p=0.35) and ICU mortality (p=0.26). CONCLUSION: After OHCA, therapeutic hypothermia is associated with an increased risk of early onset pneumonia. This complication was associated with prolonged respiratory support and ICU stay but did not significantly influence ICU mortality.

PMID: 21816940 [PubMed - as supplied by publisher]

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How to Treat Stage D Heart Failure?

Circ J Start a Discussion »

Aug 082011

How to Treat Stage D Heart Failure?

Circ J. 2011 Aug 2;

Authors: Kinugawa K

The new classification of heart failure in the American College of Cardiology/American Heart Association guidelines includes stage D, which is refractory severe heart failure that does not respond to medical or resynchronization therapy. Among the many treatment strategies for stage D heart failure, only heart transplantation and ventricular assist devices have been established as improving prognosis. With the evolution in the mechanics of ventricular assist devices in recent years, the postoperative prognosis has improved, and less sick patients can now be candidates for these devices. In Japan, 2 continuous flow devices have been approved since April 2011, and now is the best time to consider the indications for their use.

PMID: 21817817 [PubMed - as supplied by publisher]

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Physician and patient perceptions of the route of administration of venous thromboembolism prophylaxis: Results from an international survey.

Thromb Res Start a Discussion »

Aug 082011

Physician and patient perceptions of the route of administration of venous thromboembolism prophylaxis: Results from an international survey.

Thromb Res. 2011 Aug 2;

Authors: Cimminiello C, Anderson FA

INTRODUCTION: Acceptability of a prescribed treatment regimen is crucial to its clinical success, and the route of drug administration can play an important role in determining acceptability. This international survey explored physician and patient perceptions of injectable and oral treatments, and how these perceptions affect acceptability of treatments. Findings are discussed in the context of patient acceptance of treatments for venous thromboembolism (VTE) management. METHODS: Physicians who are regular prescribers of VTE prophylaxis and a randomly selected patient population were recruited to take part in a questionnaire. Patients had to answer 23 questions and physicians gave their predictions of patients' responses. RESULTS: In total, 568 physicians and 825 patients from 5 countries took part in the survey. More patients considered injectable treatments effective than considered oral treatments effective (87% versus 76%, respectively). This trend was well predicted by the physicians (98% and 61%, respectively). Additionally, 46% of patients would accept an injectable treatment program lasting >2months (rising to 67% for life-threatening diseases), a figure underestimated by physicians (11% and 46%, respectively). Overall, 73% of patients stated they would never miss an injection, where as 54% of physicians expected patients to miss one injection in a month of therapy. CONCLUSIONS: Physicians who are regular prescribers of VTE prophylaxis underestimate patients' ability to accept injectable treatments as an alternative to oral therapy. This survey suggests that injectable treatments may be an acceptable, and often preferred, option over oral administration of therapeutic and preventive medicines.

PMID: 21816454 [PubMed - as supplied by publisher]

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Dabigatran etexilate: A novel oral direct thrombin inhibitor.

Am J Health Syst Pharm Start a Discussion »

Aug 082011

Dabigatran etexilate: A novel oral direct thrombin inhibitor.

Am J Health Syst Pharm. 2011 Aug 15;68(16):1506-19

Authors: Blommel ML, Blommel AL

Purpose The pharmacology, pharmacokinetics, clinical efficacy, tolerability, dosage and administration, and place in therapy of dabigatran etexilate are reviewed. Summary Dabigatran is a reversible direct thrombin inhibitor (DTI) that has rapid and predictable anticoagulant effects and does not require the anticoagulation monitoring seen with oral vitamin K antagonists. Dabigatran etexilate has demonstrated efficacy in several clinical studies in preventing venous thromboembolism (VTE) for patients undergoing total hip or knee replacement, in preventing strokes in patients with nonvalvular atrial fibrillation, and in treating acute VTE. Dabigatran etexilate is a prodrug that is orally absorbed and completely converted to the active form dabigatran by carboxylesterases. Neither the conversion of dabigatran etexilate nor the metabolism of active dabigatran involves the cytochrome P-450 isoenzyme system. Other than hemorrhage, dabigatran is generally well tolerated, with gastrointestinal effects being the most commonly reported adverse events. All dosages should be adjusted in patients with reduced renal function. Dabigatran is currently being investigated for several thromboembolic disorders. It was approved by the Food and Drug Administration in October 2010 for stroke and VTE prevention in adult patients with nonvalvular atrial fibrillation, and it was approved by the European Medicines Agency in March 2009 for the prevention of VTE in adult patients undergoing elective total hip or knee replacement. Conclusion Dabigatran etexilate, the first oral DTI marketed in the United States, is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Dabigatran may be a viable option for anticoagulation in some patients due to its oral administration, rapid onset of action, and predictable anticoagulant effects.

PMID: 21817082 [PubMed - in process]

Link to Article at PubMed

Extreme Obesity and Outcomes in Critically Ill Patients.

Chest Start a Discussion »

Aug 082011

Extreme Obesity and Outcomes in Critically Ill Patients.

Chest. 2011 Aug 4;

Authors: Martino JL, Stapleton RD, Wang M, Day AG, Cahill NE, Dixon AE, Suratt BT, Heyland DK

Abstract BACKGROUND: Recent literature suggests that obese critically ill patients do not have worse outcomes. However, outcomes in extreme obesity (body mass index [BMI] ?40kg/m2) are unclear. We sought to determine the association between extreme obesity and intensive care unit (ICU) outcomes. METHODS: We analyzed data from a multicenter international observational study of ICU nutrition practices that occurred in 355 ICUs in 33 countries during 2007-2009. Included patients were mechanically ventilated adults >18 years who remained in the ICU for >72 hours. Using generalized estimating equations and Cox proportional hazard modeling with clustering by ICU and adjusting for potential confounders, we compared extremely obese to normal weight patients in terms of duration of mechanical ventilation (DMV), ICU length of stay (LOS), hospital LOS, and 60-day mortality. RESULTS: Of the 8813 patients included in this analysis, 3490 were normal weight (BMI 18.5-24.9kg/m2), 348 had BMI 40-49.9kg/m2, 118 had BMI 50-59.9kg/m2, and 58 had BMI?60kg/m2. Unadjusted analyses suggested that extremely obese critically ill patients have improved mortality (odds ratio for death 0.77, 95% CI 0.62-0.94), but this association was not significant after adjustment for confounders. However, an adjusted analysis of survivors found that extremely obese patients have a longer DMV and ICU LOS, with the most obese patients (BMI ?60kg/m2) also having longer hospital LOS. CONCLUSIONS: During critical illness, extreme obesity is not associated with a worse survival advantage compared to normal weight. However, among survivors, BMI?40kg/m2 is associated with longer time on mechanical ventilation and in the ICU. These results may have prognostic implications for obese critically ill patients.

PMID: 21816911 [PubMed - as supplied by publisher]

Link to Article at PubMed

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