The public health mantra about cholesterol has always been “the lower, the better.”
This has been reflected in expert guidelines which have called on doctors to aggressively lower their patient’s ‘bad’ LDL-cholesterol (LDL-C) with statin drugs to prevent heart disease.
However, our new analysis published in JAMA Internal Medicine (paywalled) challenges that notion.
Over the years, influential researchers such as the Cholesterol Treatment Trialists (CTT) at Oxford University, have monopolised the scientific debate on statins.
They have stated that for every 1mmol/L reduction in LDL-C, there is a 21% relative risk reduction in cardiovascular events.
But there are three problems with the various CTT analyses:
1. The CTT researchers have acquired all the individual patient data (raw data) from published trials and will not share them with other researchers, thus preventing independent replication of their results. For this reason, our study used published trial data only.
2. The CTT promotes the view that statins can reduce “cardiovascular events” which is a composite endpoint with inherent problems. It combines objective outcomes such as death, heart attack and stroke (hard endpoints), together with subjective outcomes such as hospital admissions or revascularisations (soft endpoints). The soft endpoints are often based on a doctor’s ‘judgement call’ and therefore subject to bias. In some analyses, these can make up the majority of events so they can skew the overall result towards benefits for the less serious cardiovascular outcomes. To avoid this, we restricted our analysis to hard endpoints only (death, heart attack and stroke), making it less prone to bias.
3. The CTT and public health authorities often promote the benefits of statins in terms of a relative risk reduction (RRR), rather than an absolute risk reduction (ARR). The RRR is a more impressive statistic (demonstrated below) and can mislead the patient into believe the benefits are larger than they are. Therefore, our study reported both the RRR and ARR of statins on cardiovascular outcomes.