This study of patients with atherosclerotic cardiovascular disease also noted that the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid than in the placebo group (n=162 [10.9%] vs. 53 [7.1%]), as was the incidence of gout (n=18 [1.2%] vs. 2 [0.3%]). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 0.5 mmol/L, representing a change of −16.5% from baseline (difference vs. placebo in change from baseline, –18.1%; p<0.001).
An editorial commenting on safety notes that in further analyses of nonprimary and secondary end points, there were additional potentially troubling signals, although the 95% confidence intervals were wide: 0.9% of the patients treated with bempedoic acid died, as compared with 0.3% in the placebo group (relative risk, 3.24; 95% CI, 0.73 to 14.34); 0.4% of the patients in the bempedoic acid group and 0.1% on placebo died from adjudicated cardiovascular disease (2.99, 0.36 to 24.82); and 0.6% and 0.1%, respectively, were hospitalised for heart failure (4.49; 0.57 to 35.38). It adds however that although the findings are potentially alarming, the imprecision that is reflected in the 95% confidence intervals renders the relative risk values virtually meaningless.
It sums up what the cumulative data from randomised treatment trials and from studies of human genetics say about ACL inhibition:
1. For a given reduction in LDL cholesterol level, drugs that inhibit ought to yield reductions in the risk of cardiovascular disease that are similar to those achieved with statins.
2. Analysis of end points in treatment trials for which there is marginal statistical power is best avoided; fortunately for bempedoic acid, an ongoing phase 3, cardiovascular outcome trial (CLEAR Outcomes) will provide additional information.
3. More broadly, with unprecedented availability of open-access biobanks that are linked to electronic medical records and genomewide genotyping and emerging phenotyping, the genetic characterisation of drug targets is set to revolutionize how medicines are developed.