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Randomized Controlled Trial
. 2021 Nov 16;10(22):e021418.
doi: 10.1161/JAHA.121.021418. Epub 2021 Nov 15.

Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes

Gjin Ndrepepa  1 , Franz-Josef Neumann  2 , Maurizio Menichelli  3 , Isabell Bernlochner  4   5 , Gert Richardt  6 , Jochen Wöhrle  7 , Bernhard Witzenbichler  8 , Katharina Mayer  1 , Salvatore Cassese  1 , Senta Gewalt  1 , Erion Xhepa  1 , Sebastian Kufner  1 , Hendrik B Sager  1   5 , Michael Joner  1   5 , Tareq Ibrahim  4 , Karl-Ludwig Laugwitz  4   5 , Heribert Schunkert  1   5 , Stefanie Schüpke  1   5 , Adnan Kastrati  1   5
Affiliations
Randomized Controlled Trial

Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes

Gjin Ndrepepa et al. J Am Heart Assoc. .

Abstract

BACKGROUND Whether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown. METHODS AND RESULTS This study included 4018 patients with acute coronary syndrome recruited in the ISAR-REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all-cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P=0.267). All-cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P=0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89-2.28]; HRC: HR, 1.33 [95% CI, 1.04-1.72]; P for interaction=0.800). CONCLUSIONS Patients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1-year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Keywords: mortality; prasugrel; randomized controlled trial; recruitment center; ticagrelor.

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Conflict of interest statement

Dr Neumann reports lectures fees paid to his institution from Amgen, Bayer Healthcare, Biotronic, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Ferrer, Pfizer, and Novartis; consultancy fees paid to his institution from Boehringer Ingelheim; grant support from Bayer Healthcare, Boston Scientific, Biotronic, Edwards Lifesciences, GlaxoSmithKline, Medtronic, Pfizer, and Abbot Vascular. Dr Kufner reports speaker fees from AstraZeneca and speaker and consulting fees from Bristol Myers Squibb not related to the current work. Dr Sager reports funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program, the Else‐Kröner‐Fresenius‐Stiftung, the Deutsche Herzstiftung, and the Deutsche Forschungsgemeinschaft. Dr Joner reports personal fees from Biotronik, Orbus Neich, AstraZeneca, and Recor; grants and personal fees from Boston Scientific and Edwards Lifesciences; and grants from Amgen. Dr Schunkert reports personal fees from Merck Sharp & Dohme, Amgen, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi‐Sankyo, Novartis, Servier, Brahms, Bristol‐Myers Squibb, Medtronic, Sanofi Aventis, Synlab, Pfizer, and Vifor as well as grants and personal fees from AstraZeneca. The remaining authors have no disclosures to report.

Figures

Figure. 1
Figure. 1. Clinical outcomes according to recruitment center volume
Left, Primary end point (composite of all‐cause death, myocardial infarction, or stroke). Right, secondary end point of bleeding. BARC indicates Bleeding Academic Research Consortium; HR, hazard ratio; HRC, high recruitment center; and LRC, low recruitment center.
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References

    1. Schulz KF. Randomised trials, human nature, and reporting guidelines. Lancet. 1996;348:596–598. DOI: 10.1016/S0140-6736(96)01201-9. - DOI - PubMed
    1. Pocock SJ, Elbourne DR. Randomized trials or observational tribulations? N Engl J Med. 2000;342:1907–1909. DOI: 10.1056/NEJM200006223422511. - DOI - PubMed
    1. Kaul S, Diamond GA. Trial and Error. How to avoid commonly encountered limitations of published clinical trials. J Am Coll Cardiol. 2010;55:415–427. DOI: 10.1016/j.jacc.2009.06.065. - DOI - PubMed
    1. Unverzagt S, Prondzinsky R, Peinemann F. Single‐center trials tend to provide larger treatment effects than multicenter trials: a systematic review. J Clin Epidemiol. 2013;66:1271–1280. DOI: 10.1016/j.jclinepi.2013.05.016. - DOI - PubMed
    1. Pocock SJ, Clayton TC, Stone GW. Design of major randomized trials: Part 3 of a 4‐part series on statistics for clinical trials. J Am Coll Cardiol. 2015;66:2757–2766. DOI: 10.1016/j.jacc.2015.10.036. - DOI - PubMed

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