Background Statins are universally recommended for the primary prevention of cardiovascular diseases (CVD). However, studies suggest that statins also increase the incidence of type 2 diabetes mellitus (T2DM), which increases the risk of CVD in the long run. Empirical studies usually have short observation periods that may underestimate the consequences of living with diabetes. This modelling study aimed to quantify the 20-year impact of statins on CVD primary prevention adjusted for the T2DM harms.

Methods We used the IMPACT_NCD validated dynamic stochastic microsimulation to simulate four scenarios: 1) the base-case scenario with statin utilisation informed by the Health Survey for England; 2) in the cohort eligible for primary prevention of CVD in 2020, simulants without known T2DM aged 40–49 are prescribed Atorvastatin 20mg daily; 3) for the remaining two scenarios we changed the age to start statin at 50–59, and 60–69, respectively. The microsimulation was developed in R v4.0.4.

High-quality meta-analyses of randomised controlled trials informed the effect of statins on CVD risk reduction and T2DM incidence. Informed by the same meta-analyses, we assumed a mean lag time of 4 years between the intervention and its effects. Based on evidence from Wales, we assumed that every year 2.5% discontinue statins. We additionally assumed a mean adherence of 82% based on evidence from Denmark.

Results Preliminary results suggest that over 20 years and compared to the base-case, statins could prevent or postpone approximately 670 (95% Uncertainty Interval (UI): 160 to 1640) cases of CVD and cause approximately 330 (95% UI: 0 to 1100) new cases of T2DM in the 40–49 cohort. These estimates increased to approximately 3800 (95% UI: 2500 to 5500) CVD cases and 2300 (95% UI:300 to 4800) T2DM case incidents in the 50–59 cohort, and 6800 (95% UI: 3900 to 8900) CVD cases and 5130 (95% UI:1450 to 10400) T2DM case incidents in the 60–69 cohort. The probabilities of statins causing more harm than benefit using quality-adjusted life-years as a measure were 22%, 7%, and 13% for the 40–49, 50–59 and 60–69 cohorts, respectively. These probabilities were substantially larger between non-white (32%, 28%, and 44% respectively) reflecting a higher T2DM baseline risk among some ethnic groups.

Conclusion This modelling study provides evidence that the overall benefits from statins for primary CVD prevention outweigh the potential harms over 20 years. However, for non-white individuals, the balance may be unfavourable for specific cohorts, guaranteeing further investigation with empirical studies.