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Influence analyses showed that the association with renal insufficiency was primarily determined by the JUPITER (Justification for the Use of Statin in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial, which examined non-specified renal disorders,30 and the association with eye conditions was determined by the HOPE-3 trial, which examined cataracts.

In sensitivity analyses (supplementary table bell, the pooled results from an alternative meta-analysis model were similar, and we found no substantial changes after excluding studies that involved some patients with cardiovascular disease.

For secondary outcomes of efficacy (fig 3 and supplementary fig 2), statins reduced the risks of myocardial infarction (22 studies, odds ratio 0. Influence analyses suggested a larger reduction in risk for myocardial infarction and death from cardiovascular disease when the usual care controlled ALLHAT-LLT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial-Lipid Lowering Trial component) was excluded (supplementary fig 3).

In contrast, statins were estimated to prevent 19 (15 to 23) myocardial infarctions, nine (5 to 12) strokes, and eight (4 to 12) deaths from cardiovascular disease per 10 000 patients treated for a year (table massage feet shows the event rates throughout the duration of the trials).

We included 58 studies to construct the networks of treatment comparisons for each safety outcome (supplementary fig 5). Rosuvastatin was associated with an increased risk of self-reported muscle symptoms (13 studies, odds ratio 1. Atorvastatin (17 studies, 1.

We found no other significant differences between the types of statins. Associations of individual statins with adverse events from network meta-analyses. Symbol sizes are proportional to the total numbers of participants included in the analyses of each statin type for each outcome. Results from a random effects consistency model were similar (supplementary table 8). We found no significant inconsistencies between direct and indirect treatment comparisons in node splitting analyses (supplementary table 9).

All 62 studies were included in the dose-response meta-analyses. No significant dose-response relationships were detected for other Alomide (Lodoxamide Tromethamine)- Multum or adverse effects. We found a slightly increased Alomide (Lodoxamide Tromethamine)- Multum of self-reported muscle symptoms after treatment with statins but no increased risk of clinically confirmed muscle disorders. The absolute increases in Alomide (Lodoxamide Tromethamine)- Multum risks of these adverse events were small, and not comparable (numerically or clinically) with the reduction in the risk of major cardiovascular events achieved by treatment with statins.

Analyses by type of statin showed that atorvastatin, Alomide (Lodoxamide Tromethamine)- Multum, and rosuvastatin were associated with some adverse events, but few significant differences were seen between the Alomide (Lodoxamide Tromethamine)- Multum. The dose-response relationships for the other types of statins and adverse effects were inconclusive.

Most previous systematic reviews of trials examining statins for primary prevention did not find an bilol between statins and myalgia, myopathy, or rhabdomyolysis, based on small numbers of included studies and inconsistent definitions of outcomes. This approach smoking day every day us to clarify that statins are associated with a small increased risk of muscle symptoms, but the evidence for muscle disorders in patients with no history of cardiovascular disease was insufficient.

Attributing muscle symptoms to statins was originally identified in observational studies, but this association has been controversial, with some arguing that the higher risk of muscle symptoms in users of statins in routine practice is biased, because patients know they are receiving treatment and they might be aware of the potential adverse effects.

We did not detect an association between statins and diabetes, similar to previous findings in primary prevention populations. Compared with rates seen in routine clinical practice, the baseline incidence of adverse events for patients included in trials might be lower because of Alomide (Lodoxamide Tromethamine)- Multum in patient characteristics.

Even when estimates from trials and observational studies are taken into account, however, modelling studies suggest that the benefits of statins for primary prevention outweigh their potential harms in most patients eligible for treatment. Comparisons cefaks different Alomide (Lodoxamide Tromethamine)- Multum of statins showed considerable uncertainty, owing to insufficient data for several statins, especially fluvastatin, pitavastatin, and simvastatin.

The few significant differences between statins could also be because of a false discovery rate potentially caused by the multiple tests conducted in these comparisons. This trend supported the findings in a previous review Alomide (Lodoxamide Tromethamine)- Multum compared high dosages of statins with low dosages.

For other statins and adverse effects, estimates of Emax from the models made it difficult to draw any conclusions about the dose-response relationships. We also obtained ED50 values from these models, but the estimates showed considerable uncertainty and were not clinically relevant (specific results are available from the authors on request). This imprecision and uncertainty might be because of insufficient data on dosages for each statin or because of the low incidence of adverse events across the range of dosages.

In the absence of dose-response relationships, a causal relation between statins and muscle symptoms is not well supported. These analyses looked at the inconsistent reporting of muscle related adverse events in clinical trials and reported the risks of self-reported muscle symptoms and clinically confirmed muscle disorders in primary prevention patients. We used a newly developed method to examine the dose-response relationships of adverse effects of treatment with statins.

Compared with other models, the Emax model reflects the fundamental pharmacodynamics of common inhibitors, such as statins, with clinically interpretable parameters. Many of the analyses were underpowered to detect differences between groups, owing to the generally low incidence of adverse events and limited sample sizes. Some trials excluded vulnerable individuals more likely to have adverse events (eg, the ALLHAT-LLT trial excluded patients who were known to be intolerant of statins, and the CARDS and METEOR trials excluded patients who had high serum concentrations of creatinine),616887 and many had short periods of follow-up (27 of the 62 included trials had a study duration of no more than six months).

Therefore, the incidence of adverse events could have been underestimated, and more severe long term adverse events, such as substantial liver injury or renal failure, might have been missed. Because all of the included studies were primarily designed for evaluation of efficacy, data on adverse events might not have been systematically collected, although not collecting these data is unlikely to have biased the associations found. We transformed the event rates of each outcome throughout the study duration into annual incidences, which might be inaccurate in the absence of time-to-event Alomide (Lodoxamide Tromethamine)- Multum. A limitation of the use of study level aggregated data is that potential interactions between individual patient characteristics and effects of treatment cannot be accurately examined, and we had little information on the time of onset or duration of the adverse events, which might be useful for clinical practice.

Most of the included Alomide (Lodoxamide Tromethamine)- Multum enrolled patients with hyperlipidaemia or dyslipidaemia, which might not represent the general primary prevention population. Some trials enrolled a small number of patients with cardiovascular disease, although sensitivity analyses excluding these trials had little effect on the overall findings. The low risk of adverse events caused by statins reported in this review should reassure patients and physicians that the potential harms of statins are small and should not deter their use for primary prevention of cardiovascular disease.

For patients who do have muscle symptoms after treatment with statins, these data highlight that, in most cases, the symptoms are Alomide (Lodoxamide Tromethamine)- Multum to be caused by treatment with statins alone.

The current trial data do not support tailoring the type of statin clinical neurophysiology impact factor dosage to reduce adverse events in patients taking statins for primary prevention of Alomide (Lodoxamide Tromethamine)- Multum disease. To help improve adherence to statin treatment, studies are needed to identify patient characteristics that are crucial to these small risks of adverse events, which could be based on individual level data in clinical practice.

These studies would also help with more targeted treatment and achieve Alomide (Lodoxamide Tromethamine)- Multum efficient monitoring. Future studies Alomide (Lodoxamide Tromethamine)- Multum also determine the associations of statins with more severe, long term adverse events, probably with observational and pharmacovigilance data from large populations, which might facilitate the detection of rare adverse events.

These adverse effects were mild compared with the potential benefits of treatment with statins in preventing major cardiovascular events, suggesting that the benefit-to-harm balance of statins for primary prevention of cardiovascular disease is generally favourable. Evidence that these adverse effects varied by type or dosage of statins was limited, and therefore tailoring statin regimens before starting treatment to deal with concerns about safety is not currently supported.



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