ROUEN, France, Feb. 28 -- Statin-related adverse effects are rare, and rarer still are tendinous complications, according to a large French post-marketing surveillance program.


Tendinous complications accounted for about 2% of all statin adverse events reported to the French pharmacovigilance network from 1990 to 2005. For the individual years reviewed, the proportion of statin-related adverse effects that involved tendons ranged from 0% to 3.6%.


"Our series suggests that statin-attributed tendinous complications are rare, considering the huge number of statin prescriptions," the authors concluded. "We suggest that prescribers should be aware of tendinous complications related to statins, particularly in risk situations, including physical exertion and association with medications known to increase the toxicity of statins."


Statin-associated tendon impairment had not been reported in previous pre- and postmarketing studies, although sporadic anecdotal reports suggested a possible link. To explore the issue more closely, Dr. Marie and associates retrospectively reviewed data from 31 French pharmacovigilance centers.


For the 16-year period reviewed, 4,597 statin-related adverse events were reported to the pharmacovigilance network. Of those, 96 events (2.01%) involved tendon impairment, consisting of 63 reports of tendinitis and 33 reports of tendon rupture. The Achilles tendon was the affected area in 50 (52.1%) of the cases, and 26 patients (27%) had bilateral tendon manifestations.


The median time to onset of tendon symptoms was 243 days, but occurred as early as 24 hours after starting therapy and as late as 15 years. Tendon symptoms occurred within the first year in 59% of patients.


Statin-attributed tendon complications were considered serious in 36 cases, and 17 patients required hospitalization. Moreover, 19 of the 33 patients who had tendon rupture had significant functional sequelae that included difficulty walking, decreased range of motion, and pain. Of seven patients who stopped and then reinitiated statin therapy, all seven had a recurrence of tendon symptoms.


Tendon complications were reported in patients treated with atorvastatin (Lipitor), simvastatin, pravastatin, fluvastatin (Lescol), and rosuvastatin (Crestor). The authors reported that the complications occurred at recommended dose ranges for all of the drugs.


Predisposing factors beyond statin therapy that might have led to tendon complications were not explored.


Though generally considered safe and associated with minor side effects, statins occasionally cause serious complications, especially musculoskeletal effects that include myositis, rare cases of rhabdomyolysis, and inflammatory myopathies. In clinical trials of statins, myositis occurred in 0.09% to 0.63% of patients and rhabdomyolysis in 1 case per 100,000 patient-years, the authors noted.


Despite their findings, the authors left the door open to the possibility that statins have a closer association with tendon problems than currently recognized. They noted that a literature review uncovered 43 cases of statin-related tendon complications.


"Tendinous manifestations may be an as-yet unreported side effect of statin therapy," they said. "In essence, no cases were reported during the large therapeutic trials, including more than 30,000 patients. However, the fact that statin-related tendon complications have not been described in these large clinical trials may be explained in part by control of factors predisposing to tendinopathy and regular follow-up of trial patients."


They concluded that this literature review suggests that tendon manifestations may be included within the spectrum of adverse effects of statins but future case-control studies are required to confirm this relationship.


"Our study suggests that regular tendinous clinical examination may be required in statin-treated patients, particularly during the first year following statin therapy initiation," they added.


The authors had no disclosures.

Source reference:
Marie I, et al "Tendinous disorders attributed to statins: A study on ninety-six spontaneous reports in the period 1990-2005 and review of the literature" Arthritis Rheum 2008; 59: 367-372.