| Abstract
|
OBJECTIVE:
To quantify the unintended effects of statins according to type, dose,
and duration of use.
DESIGN: Prospective open cohort study using routinely collected data.
SETTING: 368 general practices in England and Wales supplying data to
the QResearch database.
PARTICIPANTS: 2 004 692 patients aged 30-84 years of whom 225 922 (10.7%)
were new users of statins: 159 790 (70.7%) were prescribed simvastatin,
50 328 (22.3%) atorvastatin, 8103 (3.6%) pravastatin, 4497 (1.9%) rosuvastatin,
and 3204 (1.4%) fluvastatin.
METHODS: Cox proportional hazards models were used to estimate effects
of statin type, dose, and duration of use. The number needed to treat
(NNT) or number needed to harm (NNH) was calculated and numbers of additional
or fewer cases estimated for 10 000 treated patients.
MAIN OUTCOME MEASURE: First recorded occurrence of cardiovascular disease,
moderate or serious myopathic events, moderate or serious liver dysfunction,
acute renal failure, venous thromboembolism, Parkinson's disease, dementia,
rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer,
oesophageal cancer, colon cancer, lung cancer, melanoma, renal cancer,
breast cancer, or prostate cancer.
RESULTS: Individual statins were not significantly associated with risk
of Parkinson's disease, rheumatoid arthritis, venous thromboembolism,
dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer,
melanoma, renal cancer, breast cancer, or prostate cancer. Statin use
was associated with decreased risks of oesophageal cancer but increased
risks of moderate or serious liver dysfunction, acute renal failure, moderate
or serious myopathy, and cataract. Adverse effects were similar across
statin types for each outcome except liver dysfunction where risks were
highest for fluvastatin. A dose-response effect was apparent for acute
renal failure and liver dysfunction. All increased risks persisted during
treatment and were highest in the first year. After stopping treatment
the risk of cataract returned to normal within a year in men and women.
Risk of oesophageal cancer returned to normal within a year in women and
within 1-3 years in men. Risk of acute renal failure returned to normal
within 1-3 years in men and women, and liver dysfunction within 1-3 years
in women and from three years in men. Based on the 20% threshold for cardiovascular
risk, for women the NNT with any statin to prevent one case of cardiovascular
disease over five years was 37 (95% confidence interval 27 to 64) and
for oesophageal cancer was 1266 (850 to 3460) and for men the respective
values were 33 (24 to 57) and 1082 (711 to 2807). In women the NNH for
an additional case of acute renal failure over five years was 434 (284
to 783), of moderate or severe myopathy was 259 (186 to 375), of moderate
or severe liver dysfunction was 136 (109 to 175), and of cataract was
33 (28 to 38). Overall, the NNHs and NNTs for men were similar to those
for women, except for myopathy where the NNH was 91 (74 to 112).
CONCLUSIONS: Claims of unintended benefits of statins, except for oesophageal
cancer, remain unsubstantiated, although potential adverse effects at
population level were confirmed and quantified. Further studies are needed
to develop utilities to individualise the risks so that patients at highest
risk of adverse events can be monitored closely.
|
