Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): A multicentre, randomised, double-blind, placebo-controlled trial

Giora Weisz, Philippe Généreux, Andres Iñiguez, Aleksander Zurakowski, Michael Shechter, Karen P. Alexander, Ovidiu Dressler, Anna Osmukhina, Stefan James, E. Magnus Ohman, Ori Ben-Yehuda, Ramin Farzaneh-Far, Gregg W. Stone

Research output: Contribution to journalArticle

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Abstract

Background Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. Methods We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≤18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≤50% diameter stenosis in a coronary artery ≤2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. Findings Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). Interpretation Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. Funding Gilead Sciences, Menarini.

Original languageEnglish (US)
Pages (from-to)136-145
Number of pages10
JournalThe Lancet
Volume387
Issue number10014
DOIs
StatePublished - Jan 9 2016
Externally publishedYes

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Percutaneous Coronary Intervention
Placebos
Ischemia
Hospitalization
Acute Coronary Syndrome
Random Allocation
Ranolazine
Intention to Treat Analysis
Russia
Israel
Drug-Related Side Effects and Adverse Reactions
Coronary Vessels
Pathologic Constriction
History
Research Personnel
Drug Therapy
Mortality

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Weisz, Giora ; Généreux, Philippe ; Iñiguez, Andres ; Zurakowski, Aleksander ; Shechter, Michael ; Alexander, Karen P. ; Dressler, Ovidiu ; Osmukhina, Anna ; James, Stefan ; Ohman, E. Magnus ; Ben-Yehuda, Ori ; Farzaneh-Far, Ramin ; Stone, Gregg W. / Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI) : A multicentre, randomised, double-blind, placebo-controlled trial. In: The Lancet. 2016 ; Vol. 387, No. 10014. pp. 136-145.
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abstract = "Background Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. Methods We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≤18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≤50{\%} diameter stenosis in a coronary artery ≤2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. Findings Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98{\%}) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26{\%}) patients assigned to ranolazine and 364 (28{\%}) patients assigned to placebo (hazard ratio 0·95, 95{\%} CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14{\%}) patients in the ranolazine group and 137 (11{\%}) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). Interpretation Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. Funding Gilead Sciences, Menarini.",
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Weisz, G, Généreux, P, Iñiguez, A, Zurakowski, A, Shechter, M, Alexander, KP, Dressler, O, Osmukhina, A, James, S, Ohman, EM, Ben-Yehuda, O, Farzaneh-Far, R & Stone, GW 2016, 'Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): A multicentre, randomised, double-blind, placebo-controlled trial', The Lancet, vol. 387, no. 10014, pp. 136-145. https://doi.org/10.1016/S0140-6736(15)00459-6

Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI) : A multicentre, randomised, double-blind, placebo-controlled trial. / Weisz, Giora; Généreux, Philippe; Iñiguez, Andres; Zurakowski, Aleksander; Shechter, Michael; Alexander, Karen P.; Dressler, Ovidiu; Osmukhina, Anna; James, Stefan; Ohman, E. Magnus; Ben-Yehuda, Ori; Farzaneh-Far, Ramin; Stone, Gregg W.

In: The Lancet, Vol. 387, No. 10014, 09.01.2016, p. 136-145.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI)

T2 - A multicentre, randomised, double-blind, placebo-controlled trial

AU - Weisz, Giora

AU - Généreux, Philippe

AU - Iñiguez, Andres

AU - Zurakowski, Aleksander

AU - Shechter, Michael

AU - Alexander, Karen P.

AU - Dressler, Ovidiu

AU - Osmukhina, Anna

AU - James, Stefan

AU - Ohman, E. Magnus

AU - Ben-Yehuda, Ori

AU - Farzaneh-Far, Ramin

AU - Stone, Gregg W.

PY - 2016/1/9

Y1 - 2016/1/9

N2 - Background Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. Methods We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≤18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≤50% diameter stenosis in a coronary artery ≤2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. Findings Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). Interpretation Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. Funding Gilead Sciences, Menarini.

AB - Background Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. Methods We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≤18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≤50% diameter stenosis in a coronary artery ≤2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. Findings Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). Interpretation Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. Funding Gilead Sciences, Menarini.

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