Efficacy of long detection interval implantable cardioverter-defibrillator settings in secondary prevention population: data from the Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) trial.
BACKGROUND
Three trials demonstrated recently that a long detection window reduces implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) was the only trial that enrolled both primary and secondary prevention patients.


RESULTS
Of the 1902 patients enrolled in the ADVANCE III trial, 477 received a defibrillator for secondary prevention; 248 patients were randomly assigned to a long detection setting (30 of 40 intervals) and 229 to the nominal setting (18 of 24 intervals) for ventricular arrhythmias with cycle length ≤ 320 ms. Eight-five percent of patients were men, with a mean age of 65 ± 12 years, a previous history of ventricular fibrillation in 37% of the cases, and a mean ejection fraction of 38 ± 13%. The ICD device mix was 37% single chamber, 47% dual chamber, and 16% triple chamber. Over a median period of 12 months, the long detection period was associated with a 25% reduction in the number of overall therapies (115.6 versus 86.8 per 100 patient-years; incidence rate ratio, 0.75; 95% confidence interval, 0.61-0.93; P=0.008) and a 34% reduction in the number of shocks (rate per 100 patient-years, 51.2 versus 38.1; incidence rate ratio, 0.66; 95% confidence interval, 0.48-0.89; P=0.007). Appropriate therapies (89.7 versus 67.7; incidence rate ratio, 0.77; 95% confidence interval, 0.60-0.97; P=0.029) and appropriate shocks (37.1 versus 28.1; incidence rate ratio, 0.64; 95% confidence interval, 0.45-0.93; P=0.018) were also reduced.


CONCLUSIONS
ADVANCE III is the first randomized trial to assess a long detection window setting in ICDs in both primary and secondary prevention populations and demonstrates a reduction of overall therapies and shocks in the subgroup of secondary prevention patients. These data suggest that even the secondary prevention population may benefit from programming that combines a long detection period with antitachycardia pacing during charging.


BACKGROUND
http://www/clinicaltrials.gov. Unique identifier: NCT00617175.
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Axel
A
Kloppe
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Alessandro
A
Proclemer
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Angel
A
Arenal
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Maurizio
M
Lunati
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
José Bautista
JB
Martìnez Ferrer
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Ahmad
A
Hersi
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Marcin
M
Gulaj
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Maurits C E F
MC
Wijffels
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Elisabetta
E
Santi
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Laura
L
Manotta
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini).
Lorenza
L
Mangoni
From Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr Universität Bochum, Bochum, Germany (A.K.); Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy (A.P.); Hospital General Universitario Gregorio Marañón, Madrid, Spain (A.A.); Azienda Ospedaliera Niguarda Ca' Granda, Milano, Italy (M.L.); Hospital de Txagorritxu, Vitoria (Álava), Spain (J.B.M.F.); College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.H.); MSWiA Hospital, Bialystok, Poland (M. Gulaj); St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands (M.C.E.F.W.); Medtronic Clinical Research Institute, Rome, Italy (E.S., L. Mangoni); Medtronic Clinical Research Institute, Sesto San Giovanni, Italy (L. Manotta); and Humanitas Research Hospital, Rozzano-Milano, Italy (M. Gasparini). maurizio.gasparini@humanitas.it.
Maurizio
M
Gasparini
D000368:Aged; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000009:adverse effects / Q000379:methods*; D004868:Equipment Failure; D005260:Female; D006339:Heart Rate; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention; D055502:Secondary Prevention; D016037:Single-Blind Method; D013318:Stroke Volume; D013575:Syncope / Q000453:epidemiology / Q000209:etiology; D017180:Tachycardia, Ventricular / Q000517:prevention & control* / Q000628:therapy; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000517:prevention & control* / Q000628:therapy
arrhythmia; implantable cardioverter-defibrillators; secondary prevention; stimulators, electrical, cardiac, shock