Dataset Information

Antithrombotic Therapy Recommendations in the European Society of Cardiology Guidelines: How Robust Are the Randomized Controlled Trials Underpinning Them?

ABSTRACT: Introduction Criticisms have been raised against the sole use of p -value in interpreting results from randomized controlled trials (RCTs). Additional tools have been suggested, like the fragility index (FI), a measure of a trial's robustness/fragility, and derivative measures. The FI is the minimum number of patients who would have to be converted from nonevents to events, in the group with the least events, for a result to lose statistical significance. Objective This study aimed to evaluate RCT supporting European Society of Cardiology (ESC) guidelines regarding antithrombotics, using the FI and FI-related measures. Methods FI, fragility quotient (FQ), and FI minus LTF lost to follow-up (FI - LTF) were calculated for the RCT underpinning recommendations regarding antithrombotic therapy from the updated ESC guidelines. LTF was compared with FI. Results were calculated for the total group of studies, as per guideline and as per recommendation type. Results Overall, 61 studies were included. The median FI was 24.5 (interquartile range [IQR]: 9.0-60.0) and median FQ was 0.0035 (IQR: 0.0019-0.0056). Median FI - LTF was 2.0 (IQR: 0.0-38.0). Twenty (32.8%) of the studies had one primary or main safety outcome with LTF exceeding FI. Peripheral arterial disease guideline and chronic coronary syndrome guideline had the lowest (2.5; IQR: 1.8-3.3) and the highest (48.5; IQR: 23.8-73.0) FI, respectively. Conclusion The median FI suggests robustness of clinical trials evaluating antithrombotic drugs cited in the guidelines, but about one-third of them had LTF larger than FI. This emphasizes the need for assessing trials' robustness when constructing guidelines.

SUBMITTER: Santos CMD

PROVIDER: S-EPMC8046518 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The American College of Cardiology (ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) have recently published recommendations for the use of proprotein convertase subtilisin/kexin-9 (PCSK9) inhibitors in situations of very high risk. We aim to assess in the real world the suitability of PCSK9 inhibitors for acute coronary syndromes.We analyzed a prospective Swiss cohort of 2023 patients hospitalized for acute coronary syndromes between 2009 and 2014 with available data for low-density lipoprotein cholesterol and lipid-lowering therapy at 1 year. Clinical familial hypercholesterolemia was defined using the Dutch Lipid Clinic Network algorithm as unlikely, possible, probable, or definite. We simulated a fixed relative reduction of 24% in low-density lipoprotein cholesterol levels at 1 year in all patients not treated with ezetimibe, irrespective of the low-density lipoprotein cholesterol levels and statin regimen. At 1 year, 94.3% of patients were treated with statin, 5.8% with ezetimibe, and 35.8% of patients had on-target low-density lipoprotein cholesterol levels (<1.8 mmol/L); 25.6% met criteria for possible or probable/definite familial hypercholesterolemia. After a simulation of the lipid-lowering effect of ezetimibe, the proportion of patients who would be eligible for PCSK9 inhibitors at 1 year was 13.4% using American College of Cardiology criteria and 2.7% using European Society of Cardiology/European Atherosclerosis Society criteria. Patients with possible or probable/definite familial hypercholesterolemia were more eligible for PCSK9 inhibitors compared with their non-familial hypercholesterolemia counterparts: 27.6% versus 8.8% according to American College of Cardiology criteria and 6.6% versus 1.8% according to European Society of Cardiology/European Atherosclerosis Society criteria (P<0.001).Recommendations made by the American College of Cardiology guidelines would lead to 5-fold higher eligibility rates for PCSK9 inhibitors compared to the European Society of Cardiology/European Atherosclerosis Society consensus statement in acute coronary syndrome patients.

Project description:ImportanceClinical decisions are ideally based on evidence generated from multiple randomized controlled trials (RCTs) evaluating clinical outcomes, but historically, few clinical guideline recommendations have been based entirely on this type of evidence.ObjectiveTo determine the class and level of evidence (LOE) supporting current major cardiovascular society guideline recommendations, and changes in LOE over time.Data sourcesCurrent American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) clinical guideline documents (2008-2018), as identified on cardiovascular society websites, and immediate predecessors to these guideline documents (1999-2014), as referenced in current guideline documents.Study selectionComprehensive guideline documents including recommendations organized by class and LOE.Data extraction and synthesisThe number of recommendations and the distribution of LOE (A [supported by data from multiple RCTs or a single, large RCT], B [supported by data from observational studies or a single RCT], and C [supported by expert opinion only]) were determined for each guideline document.Main outcomes and measuresThe proportion of guideline recommendations supported by evidence from multiple RCTs (LOE A).ResultsAcross 26 current ACC/AHA guidelines (2930 recommendations; median, 121 recommendations per guideline [25th-75th percentiles, 76-155]), 248 recommendations (8.5%) were classified as LOE A, 1465 (50.0%) as LOE B, and 1217 (41.5%) as LOE C. The median proportion of LOE A recommendations was 7.9% (25th-75th percentiles, 0.9%-15.2%). Across 25 current ESC guideline documents (3399 recommendations; median, 130 recommendations per guideline [25th-75th percentiles, 111-154]), 484 recommendations (14.2%) were classified as LOE A, 1053 (31.0%) as LOE B, and 1862 (54.8%) as LOE C. When comparing current guidelines with prior versions, the proportion of recommendations that were LOE A did not increase in either ACC/AHA (median, 9.0% [current] vs 11.7% [prior]) or ESC guidelines (median, 15.1% [current] vs 17.6% [prior]).Conclusions and relevanceAmong recommendations in major cardiovascular society guidelines, only a small percentage were supported by evidence from multiple RCTs or a single, large RCT. This pattern does not appear to have meaningfully improved from 2008 to 2018.

Dataset Information

Antithrombotic Therapy Recommendations in the European Society of Cardiology Guidelines: How Robust Are the Randomized Controlled Trials Underpinning Them?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets