other types of health outcome
Large randomized trials, and meta-analyses of those trials, have established that statin therapy rarely results in serious muscle problems known as myopathy and rhabdomyolysis (which are characterized by muscle symptoms in association with biochemical evidence of significant muscle damage) but the absolute excess risk of such complications is very small. In addition, such studies have shown that statins cause small absolute increases in the incidence of haemorrhagic stroke and of diabetes.
However, it has been postulated that statins may have additional adverse effects. To address these concerns, the CTT Collaboration plans to extend the CTT meta-analysis dataset to encompass all recorded adverse events for each of the participating trials so as to provide a more complete understanding of the nature and magnitude of any other effects (either adverse or beneficial) of statin therapy.
Planned work will examine the effects of statin therapy on:
- Adverse events that are definitely or probably increased by statin therapy (ie, myopathy, diabetes and haemorrhagic stroke): analyses of these events will examine the magnitude, timing and duration of the excess risks both overall and in particular subgroups (eg, diabetes according to baseline HbA1c, haemorrhagic stroke with or without prior stroke), and will also explore how the magnitude of the risks varies according to how an adverse event is defined (eg, biochemical versus clinical diagnosis of diabetes mellitus);
- Muscle-related symptoms: analyses of these events will consider muscle pain (ie, myalgia) and weakness separately from myopathy and will explore whether statins increase reported rates of muscle pain of different levels of severity (including, for example, muscle symptoms given as a reason for stopping study treatment);
- Other possible effects of statin therapy: this will include adverse events which have been added to some statin drug labels on the basis that there may be a class effect for such events (including cognitive impairment, depression, sleep disturbance, sexual dysfunction and interstitial lung disease), as well as adverse events for which it has been suggested there may be a reduction with statin therapy (eg, pancreatitis); and
- All other adverse events recorded in large randomized trials of statin therapy
The protocol for this project has been published: American Heart Journal 2016; 176: 63-9.
Ethics approval for the project was gained from the UK NHS Health Research Authority in March 2016.
Data sharing agreements have been finalized with the relevant parties for nearly all participating trials. A process to convert all the data into a standard universally mapped format through use of systems based upon commonly used standards including the Clinical Data Interchange Standards Consortium Study Data Tabulation Model (CDISC SDTM) and the Medical Dictionary for Regulatory Activities (MedDRA) is underway. This will enable the highly extensive (>20M data items) heterogeneous data to be converted into a single analysable database.
Further details on progress can be obtained through review of the CTT Independent Oversight Panel teleconference minutes.