Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

Abstract

In this study, we analyzed the effectiveness of statin therapy for the primary prevention of cardiovascular disease (CVD) in low- and medium-risk patients. Using observational data, we estimated effectiveness by emulating a hypothetical randomized clinical trial comparing statin initiators with statin non-initiators. Two approaches were used to adjust for potential confounding factors: matching and inverse probability weighting in marginal structural models. The estimates of effectiveness were obtained by intention-to-treat and per-protocol analysis. The intention-to-treat analysis revealed an absolute risk reduction of 7.2 (95% confidence interval (CI95%), −6.6–21.0) events per 1000 subjects treated for 5 years in the matched design, and 2.2 (CI95%, −3.9–8.2) in the marginal structural model. The per-protocol analysis revealed an absolute risk reduction of 16.7 (CI95%, −3.0–36) events per 1000 subjects treated for 5 years in the matched design and 5.8 (CI95%, 0.3–11.4) in the marginal structural model. The indication for statin treatment for primary prevention in individuals with low and medium cardiovascular risk appears to be inefficient, but improves with better adherence and in subjectvs with higher risk.

Patterns of statin adherence in primary cardiovascular disease prevention during the pandemic

“…Finally, it is also possible that a lack of in-person consultations at the beginning of the COVID-19 pandemic may have caused patients to neglect their condition, with consequent negative health outcomes. In any case, further studies will be necessary to identify the underlying reasons, and to assess the validity of prescribing statins to low-risk patients who continuously show poor adherence, resulting in poor statin effectiveness ( Chaure-Pardos et al, 2022 ). For them, alternative non-pharmacological measures might be a more appropriate choice.…”

“…However, while statin efficacy in primary prevention of CVD has been well demonstrated in clinical trials, their effectiveness in clinical practice is less clear. This is in part because the desired clinical effects are only achievable if the patient adheres to the treatment plan ( Chaure-Pardos et al, 2022 ). Adherence to long-term therapies for chronic illnesses has been described as suboptimal ( Menditto et al, 2018 ), particularly in the case of statins for primary CVD prevention ( Ofori-Asenso et al, 2018 ).…”

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

“…We retrieved 3133 unique records, of which 200 were included in the review (Figure 1). All reasons for excluding records after full-text review are given in eAppendix 6 in Supplement 1.…”

“…Seventy studies (35%) reported in the title that the study aimed to emulate a target trial; 180 (90%) did so in the Methods section. Twenty studies (10%) reported the study was prospectively registered, 16 of these 20 (80%)…”

“…Twenty studies (10%) reported the study was prospectively registered, 16 of these 20 (80%) also provided information on how to access the registration. One hundred and twenty-six studies (63%) specified whether a randomized clinical trial could be feasibly conducted; 61 (31%) stated that the randomized clinical trial was possible. Of the studies that stated a randomized clinical trial was possible, uncertainty in the generalizability of available trial findings was the most common reason for the target trial emulation (22 of 61 [36%]) .…”