Assessing the external validity of the VALIDATE-SWEDEHEART trial

Rebecca T Rylance, Philippe Wagner, Elmir Omerovic, Claes Held, Stefan James, Sasha Koul, David Erlinge, Rebecca T Rylance, Philippe Wagner, Elmir Omerovic, Claes Held, Stefan James, Sasha Koul, David Erlinge

Abstract

Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days.

Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up.

Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)).

Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.

Trial registration: ClinicalTrials.gov NCT02311231.

Keywords: VALIDATE-SWEDEHEART; anticoagulants; nationwide registry data; percutaneous coronary intervention; real-world.

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flowchart.
Figure 2.
Figure 2.
Kaplan Meier failure curves trial population.
Figure 3.
Figure 3.
Kaplan Meier failure curves screened not-enrolled with fulfilled inclusion criteria population.

References

    1. Marchand E, Stice E, Rohde P, et al.. Moving from efficacy to effectiveness trials in prevention research. Behav Res Ther 2011; 49(1): 32–41.
    1. Akobeng AK. Assessing the validity of clinical trials. J Pediatr Gastroenterol Nutr 2008; 47(3): 277–282.
    1. Dekkers OM, von Elm E, Algra A, et al.. How to assess the external validity of therapeutic trials: a conceptual approach. Int J Epidemiol 2010; 39: 89–94.
    1. Erlinge D, Omerovic E, Frobert O, et al.. Bivalirudin versus heparin monotherapy in myocardial infarction. N Eng J Med 2017; 377: 1132–1142.
    1. Rothwell PM. External validity of randomised controlled trials: ‘to whom do the results of this trial apply?’. Lancet 2005; 365: 82–93.
    1. Paul M, Bronstein E, Yahav D, et al.. External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA. BMJ Open 2015; 5: e008838.
    1. Erlinge D, Koul S, Omerovic E, et al.. Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care 2019; 8(6): 492–501.
    1. Erlinge D, Koul S, Eriksson P, et al.. Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction: a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial). Am Heart J 2016; 175: 36–46.
    1. Stuart EA, Cole SR, Bradshaw CP, et al.. The use of propensity scores to assess the generalizability of results from randomized trials. J R Stat Soc Ser A Stat Soc 2001; 174: 369–386.
    1. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multiv Behav Res 2011; 46(3): 399–424.
    1. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015; 34: 3661–3679.
    1. Pezzi A, Cavo M, Biggeri A, et al.. Inverse probability weighting to estimate causal effect of a singular phase in a multiphase randomized clinical trial for multiple myeloma. BMC Med Res Methodol 2016; 16: 150.
    1. Harder VS, Stuart EA, Anthony JC. Propensity score techniques and the assessment of measured covariate balance to test causal associations in psychological research. Psychol Methods 2010; 15(3): 234–249.
    1. Zeymer U, Rao SV, Montalescot G. Anticoagulation in coronary intervention. European Heart Journal 2016; 37: 3376–3385.
    1. Hofmann R, Svensson L, James SK. Oxygen therapy in suspected acute myocardial infarction. N Engl J Med 2018; 378: 201–202.
    1. Frobert O, Lagerqvist B, Olivecrona GK, et al.. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013; 369: 1587–1597.
    1. Grimfjard P, Erlinge D, Koul S, et al.. Unfractionated heparin versus bivalirudin in patients undergoing primary percutaneous coronary intervention: a SWEDEHEART study. Eurointervention 2017; 12: 2009–2017.
    1. Valgimigli M, Frigoli E, Leonardi S, et al.. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med 2015; 373: 997–1009.
    1. Leonardi S, Frigoli E, Rothenbuhler M, et al.. Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial. BMJ 2016; 354: i4935.
    1. Stone GW, Witzenbichler B, Guagliumi G, et al.. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218–2230.
    1. Shahzad A, Kemp I, Mars C, et al.. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet 2014; 384: 1849–1858.
    1. Makady A, de Boer A, Hillege H, et al.. What is real-world data? A review of definitions based on literature and stakeholder interviews. Value Health 2017; 20(7): 858–865.
    1. Yeh RW, Kennedy K, Spertus JA, et al.. Do postmarketing surveillance studies represent real-world populations? A comparison of patient characteristics and outcomes after carotid artery stenting. Circulation 2011; 123: 1384–1390.
    1. Yeh RW, Czarny MJ, Normand SL, et al.. Evaluating the generalizability of a large streamlined cardiovascular trial: comparing hospitals and patients in the dual antiplatelet therapy study versus the National Cardiovascular Data Registry. Circ Cardiovasc Qual Outcomes 2015; 8(1): 96–102.
    1. Junghans C, St John M. Making it back to base: how recruitment to cohort studies affects outcomes. Eur Heart J Qual Care Clin Outcomes 2018; 4: 6–7.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel