Stopping Statins in At-Risk Patients — Just Too Risky

Pharmacology Watch

Stopping statins, even briefly, after stroke or cardiovascular surgery increases vascular complications according to 3 new studies. Spanish investigators looked at 89 patients who were on chronic statin therapy and were admitted with acute stroke. Half were randomized to statin withdrawal for the first 3 days after admission, while the other half immediately received atorvastatin 20 mg/day. After 4 days, the statin withdrawal group was also started on atorvastatin. The primary outcome was death or dependence after 3 months as defined by modified Rankin scale of 2 or more. After 3 months, 60% of those in the statin withdraw group were disabled to the point of dependence compared with 39% of those that continued statin therapy (P = 0.043). Early neurologic deterioration was also far greater in the statin withdrawal group (65.2% versus 20.9%; P < 0.0001). Statin withdrawal patients also had greater infarct volume (p = 0.002). The authors conclude that statin withdrawal in the first few days after stroke is associated with a markedly increased risk of death or dependency at 90 days; hence, treatment should continue the acute phase of an ischemic stroke (Neurology 2007; 69:904-910).

In another study, researchers in Italy looked at stroke patients who discontinued statins after discharge from the hospital. The study population included 631 stroke patients (322 men, 309 women) without evidence of heart disease. All patients were discharged on a statin, but 38.9% discontinued the drug within 12 months. In the 12 months of follow-up, 116 patients died. After adjustment for all confounders and interactions, the hazard ratio for mortality in patients who quit a statin was 2.78 (95%CI, 1.96-3.72; P = 0.003) or nearly 3 times higher risk of death (Stroke 2007, published online ahead of print 8/30/07).

Another study from the Netherlands looked at a brief interruption in statin therapy associated with major vascular surgery. Nearly 300 patients on statins underwent major vascular surgery, and statin therapy was interrupted in the perioperative period in 70 patients for mean duration of 3 days. An association was observed between statin discontinuation and an increase risk of postoperative troponin release (HR 4.6) and the combination of MI and cardiovascular death combined (HR 7.5). Because many surgical patients are NPO and unable to take oral statins, and there's no intravenous statin available, the only extended release statin was tried on a subset of patients preoperatively. Patients receiving extended-release fluvastatin had fewer perioperative cardiac events compared to other statins (Am J Cardiol 2007; 100:316-320). The message of these studies is that statin interruption, even for a brief period during hospitalization, may lead to serious adverse events in patients at risk.

Mupirocin Less Effective Against MRSA

Mupirocin (Bactroban) is becoming less and less effective against MRSA, even in hospitals with low levels of mupirocin use. Researchers from Washington University in St. Louis performed nasal swab cultures for MRSA in all patients admitted to their surgical intensive care unit (SICU) on admission, weekly during hospitalization, and at discharge. Of the 302 positive MRSA isolates, 13.2% were resistant to mupirocin, with 8.6% having high-level resistance. Patients with mupirocin-resistant MRSA were more likely to be older, have a history of a previous admission in last year, and had higher in-hospital mortality. The authors conclude that patients carrying mupirocin-resistant MRSA acquired it through contact with the health-care system; the strains were probably not acquired in the SICU (Clin Infect Dis 2007; 45:541-547). Mupirocin is commonly used to decolonize patients who are staph aureus carriers or have nasal colonization with MRSA. With resistance patterns increasing nationwide, this strategy may need to change.

New Guideline for Asthma Diagnosis/Management

The National Asthma Education and Prevention Program has issued an update to their clinical practice guidelines for diagnosis and management of asthma (Expert Panel Report 3 [EPR-3]). The new guideline emphasizes the importance of asthma control and highlights 4 areas of emphasis including assessment and monitoring, patient education, control of environmental factors and other asthma triggers, and pharmacotherapy. The new guideline recommends continued use of a stepwise approach to asthma control in which medication doses or types are stepped up or down as needed based on asthma control. Recommendations now are based on 3 age groups, 0-4 years, 5-11 years (a new category), and 12 years and older.. The new age group was added because of evidence that children respond differently to medications than adults. The entire guideline can be found at:

FDA Actions

The FDA announced on August 14 that manufacturers of rosiglitazone (Avandia) pioglitazone (Actos), and other combination medications containing the 2 drugs will be required to add a "black box" warning to their labeling to reflect the risk of heart failure associated with the 2 drugs. Both drugs have been associated with reports of significant weight gain and edema, and some cases continuation of therapy has lead to poor outcomes including death. The black box warning advises health-care professionals to carefully observe patients taking these drugs for signs and symptoms of heart failure including rapid weight gain, shortness of breath, edema. The warning also recommends not starting either drug in patients with a history of congestive heart failure. The agency continues to review rosiglitazone for the possible increase risk of myocardial infarction associated with use of the drug.

The FDA has approved a new indication for zoledronic acid (Reclast) as a once-a-year treatment for postmenopausal osteoporosis. Reclast is administered as an annual 15-minute intravenous infusion. The drug is a bisphosphonate similar to oral bisphosphonates such as alendronate and risedronate.

Anesiva has received approval to market lidocaine topical powder intradermal injection system (Zingo) to provide local analgesic prior to venipuncture or peripheral intravenous cannulation in children ages 3-18. Zingo is a single-use helium powered system that is administered 1-3 minutes prior to needle insertion. The system is also being studied in trials of adults.

The FDA has approved a new combination of carbidopa, levodopa, entacapone (50 mg/200 mg/200 mg) for the treatment of Parkinson's disease. The new preparation helps reduce the pill burden for Parkinson's patients on multiple medications. Carbidopa/levodopa/entacapone will be marketed by Orion Corporation as Stalevo.

Omrix Biopharmaceuticals has received approval to market human thrombin (Evithrom) to promote blood clotting and control bleeding during surgery. Evithrom is the first human thrombin approved since 1954 and the only product currently available for this indication. It is applied to the surface of bleeding tissue during surgery and may be used in conjunction with absorbable gelatin sponge. Other thrombins currently on the market are derived from cattle plasma.

Nursing mothers who were taking codeine may put their babies at risk of morphine overdose if they are "ultra-rapid metabolizers of codeine," a condition that may affect up to 28% of the population. Codeine is generally recommended for nursing mothers as a cough suppressant and pain medication; however, ultra-rapid metabolizers quickly convert codeine to morphine and excrete it in breast milk. At least one infant death has been associated with this condition. The FDA has issued warning regarding codeine use by nursing mothers, recommending that mothers observe their infants closely while taking the medication for signs of morphine overdose including sleepiness, difficulty breast feeding, breathing difficulties or limpness.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5431. E-mail: