The effect of clinical trial regulation changes on statin therapy for cardiovascular disease in randomized controlled trials
Creators: name: Browning, Savannah Grace
Publisher: name: The University of Texas at Austin
Year: 2020
Subjects: Clinical trials
Statins
Cardiovascular disease

description: Cardiovascular disease continues to be of concern in many developed countries, especially in the United States where 1 out of 4 deaths is due to heart disease. High blood cholesterol levels are thought to be one of the major risk factors for heart disease, therefore statin therapy, alone or in combination with lifestyle changes, is one of the most common preventions and treatments for heart disease. From 2011-2012 approximately 28% of adults in the U.S 40+ reported taking a cholesterol lowering drug in the past 30 days, of those 28%, 93% report taking a statin. The believed effectiveness of statins stems from the multitude of clinical trials, and meta-analyses reporting statins were effective in decreasing the incidence of cardiac events. Clinical trial regulations have been modified substantively from time to time, with one of the largest set of changes being put into place in 2004. The changes put into place in 2004 require 1) clinical trials to be registered with a clinical trial registry, 2) registry to be kept up to date with all trial design changes, 3) all data and results must be published as it is available. Based on a set of visual evaluations, a recent comprehensive evaluation concluded that the statin clinical trials, occurring after this large scale change in regulations, reporting that statins are not efficacious as originally believed and are likely dangerous. In this thesis, de novo meta-analyses were performed evaluating the efficacy of statin therapy on the reduction in the incidence of primary cardiac outcomes, cardio-related mortality, and all-cause mortality. We posited that the 2004 regulations had an impact on reports of efficacy and thus subgroup analyses were performed distinguishing the studies that occurred prior to the major clinical trial regulation changes in 2004 (pre-2004), and those that occurred after (post-2004). Studies fitting the inclusion and exclusion criteria were identified, pertinent data were extracted, and data analyses were performed using the inverse variance heterogeneity model. In the total combined pooled analysis, studies showed results consistent with many other meta-analyses, that statin therapy was effective in reducing primary cardiac event incidence. However, among the subgroup of studies occurring after the 2004 changes, efficacy of statin therapy in reducing primary cardiac event incidence did not meet statistical significance. A similar pattern was seen in the analysis for cardio-related mortality, and all-cause mortality. We conclude that the clinical trial regulation changes that went into place in 2004 appeared to have an effect the published outcomes of clinical trials of statins. The clinical trial regulation changes altered the apparent efficacy of statin therapy regarding a decrease. Among trials conducted after the regulations, there was not a statistically significant reduction in the incidence of primary cardiac outcomes, cardio-related death, and all-cause mortality. This information shows that it will be important to continue to critically evaluate all new clinical trials, as well as the meta-analyses that include a large portion of pre-2004 studies.