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Objective <p>To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale.</p> Design <p>Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline.</p> Setting <p>Single tertiary A teaching hospital in China, March 2012 to September 2024.</p> Participants <p>Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching.</p> Main outcome measures <p>The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24–72&#xa0;h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (&gt; 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated.</p> Results <p>The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95% CI 7.13 to 7.67; <i>P</i> &lt; 0.001). Newly emerged QTc prolongation occurred in 14.7% versus 10.5% (risk ratio 1.40, 95% CI 1.35 to 1.45). The composite cardiac safety endpoint did not differ (0.4% versus 0.5%; <i>P</i> = 0.24). Results were consistent across eight subgroups and six sensitivity analyses. The TTE estimate was concordant with the published RCT finding of 7.40 ms (heterogeneity <i>P</i> = 1.00), with a 14-fold narrower confidence interval. The negative control outcome analysis showed no residual bias.</p> Conclusions <p>Rosuvastatin was associated with a 7.40 ms greater short-term QTcF prolongation than atorvastatin in a cohort 212 times larger than the emulated RCT, without excess clinical cardiac events over a mean follow-up of 48&#xa0;h. Target trial emulation successfully replicated the RCT finding for a short-term drug safety outcome, demonstrating the framework’s value for pharmacovigilance research using routine clinical data.</p>

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Short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval: a target trial emulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Xin Chen,
  • Yang Liu,
  • Wei Wei,
  • Xia Xia,
  • Xinyue Wu,
  • Xinyi Lu,
  • Gang Hu,
  • Shengdi Lu,
  • Yun Shen

摘要

Objective

To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale.

Design

Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline.

Setting

Single tertiary A teaching hospital in China, March 2012 to September 2024.

Participants

Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching.

Main outcome measures

The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24–72 h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (> 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated.

Results

The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95% CI 7.13 to 7.67; P < 0.001). Newly emerged QTc prolongation occurred in 14.7% versus 10.5% (risk ratio 1.40, 95% CI 1.35 to 1.45). The composite cardiac safety endpoint did not differ (0.4% versus 0.5%; P = 0.24). Results were consistent across eight subgroups and six sensitivity analyses. The TTE estimate was concordant with the published RCT finding of 7.40 ms (heterogeneity P = 1.00), with a 14-fold narrower confidence interval. The negative control outcome analysis showed no residual bias.

Conclusions

Rosuvastatin was associated with a 7.40 ms greater short-term QTcF prolongation than atorvastatin in a cohort 212 times larger than the emulated RCT, without excess clinical cardiac events over a mean follow-up of 48 h. Target trial emulation successfully replicated the RCT finding for a short-term drug safety outcome, demonstrating the framework’s value for pharmacovigilance research using routine clinical data.