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John Chalmers - One of the best experts on this subject based on the ideXlab platform.
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the treatment effect of an ace inhibitor based regimen with Perindopril in relation to beta blocker use in 29 463 patients with vascular disease a combined analysis of individual data of advance europa and progress trials
Cardiovascular Drugs and Therapy, 2017Co-Authors: Jasper J. Brugts, Willem J Remme, Stephen Macmahon, John Chalmers, Maarten L. Simoons, Roberto Ferrari, Michel E Bertrand, Keith Fox, Eric BoersmaAbstract:Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large Perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a Perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/Perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding Perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of Perindopril treatment are additive to the background beta-blockers use.
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effects of combination of Perindopril indapamide and calcium channel blockers in patients with type 2 diabetes mellitus results from the action in diabetes and vascular disease preterax and diamicron controlled evaluation advance trial
Hypertension, 2014Co-Authors: John Chalmers, Hisatomi Arima, Mark Woodward, Giuseppe ManciaAbstract:The objective of the present analysis was to determine the effects of a fixed combination of Perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of Perindopril–indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%–43%) among patients with CCB at baseline compared with 5% (−12% to 20%) among those without CCB ( P homogeneity=0.02) and 14% (2%–25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (−8% to 28%) versus 6% (−10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant ( P homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of Perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.
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effects of blood pressure lowering on cardiovascular outcomes in different cardiovascular risk groups among participants with type 2 diabetes
Diabetes Research and Clinical Practice, 2012Co-Authors: John Chalmers, Mark E Cooper, Susan Van Dieren, Andre Pascal Kengne, Joline W J Beulens, Diederick E Grobbee, Stephen B Harrap, Giuseppe Mancia, Bruce NealAbstract:Abstract Aims To asses differences in treatment effects of a fixed combination of Perindopril–indapamide on major clinical outcomes in patients with type 2 diabetes across subgroups of cardiovascular risk. Methods 11,140 participants with type 2 diabetes, from the ADVANCE trial, were randomized to Perindopril–indapamide or matching placebo. The Framingham equation was used to calculate 5-year CVD risk and to divide participants into two risk groups, moderate–high risk ( 25% and/or history of macrovascular disease). Endpoints were macrovascular and microvascular events. Results The mean age of participants was 66 years (42.5% female). 1000 macrovascular and 916 microvascular events were recorded over follow-up of 4.3 years. Relative treatment effects were similar across risk groups, (all P -values for heterogeneity ≥0.38). Hazard ratios for combined macro- and microvascular events were 0.89 (0.77–1.03) for the moderate-high risk and 0.92 (0.81–1.03) for the very high risk. Absolute treatment effects tended to be greater in the high risk groups although differences were not statistically significant ( P >0.05). Conclusions Relative effects of blood pressure lowering with Perindopril–indapamide on cardiovascular outcomes were similar across risk groups whilst absolute effects trended to be greater in the high risk group.
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Perindopril based blood pressure lowering reduces major vascular events in asian and western participants with cerebrovascular disease the progress trial
Journal of Hypertension, 2010Co-Authors: Hisatomi Arima, Stephen Macmahon, Bruce Neal, Christophe Tzourio, Anthony Rodgers, Mark Woodward, Craig S Anderson, Lisheng Liu, Teruo Omae, John ChalmersAbstract:ObjectiveTo assess the benefits of blood pressure (BP) lowering on vascular events separately for Asian and for Western participants with particular emphasis on stroke subtypes and cardiac outcomes.MethodsThis is a subsidiary analysis of Perindopril Protection Against Recurrent Stroke Study (PROGRES
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the consistency of the treatment effect of an ace inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease a combined analysis of individual data of advance europa and progress trials
European Heart Journal, 2009Co-Authors: Jasper J. Brugts, Willem J Remme, M E Bertrand, Stephen Macmahon, John Chalmers, Eric Boersma, Roberto Ferrari, Toshiharu Ninomiya, Maarten L. SimoonsAbstract:Aims Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of Perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. Methods and results We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a Perindopril-based treatment regimen or placebo. The Perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82–0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95% CI 0.76–0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95% CI 0.71–0.90; P < 0.001), stroke (HR 0.82; 95% CI 0.74–0.92; P = 0.002), and heart failure (HR 0.84; 95% CI 0.72–0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. Conclusion This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (Perindopril–indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.
Stephen Macmahon - One of the best experts on this subject based on the ideXlab platform.
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the treatment effect of an ace inhibitor based regimen with Perindopril in relation to beta blocker use in 29 463 patients with vascular disease a combined analysis of individual data of advance europa and progress trials
Cardiovascular Drugs and Therapy, 2017Co-Authors: Jasper J. Brugts, Willem J Remme, Stephen Macmahon, John Chalmers, Maarten L. Simoons, Roberto Ferrari, Michel E Bertrand, Keith Fox, Eric BoersmaAbstract:Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large Perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a Perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/Perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding Perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of Perindopril treatment are additive to the background beta-blockers use.
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Perindopril based blood pressure lowering reduces major vascular events in asian and western participants with cerebrovascular disease the progress trial
Journal of Hypertension, 2010Co-Authors: Hisatomi Arima, Stephen Macmahon, Bruce Neal, Christophe Tzourio, Anthony Rodgers, Mark Woodward, Craig S Anderson, Lisheng Liu, Teruo Omae, John ChalmersAbstract:ObjectiveTo assess the benefits of blood pressure (BP) lowering on vascular events separately for Asian and for Western participants with particular emphasis on stroke subtypes and cardiac outcomes.MethodsThis is a subsidiary analysis of Perindopril Protection Against Recurrent Stroke Study (PROGRES
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the consistency of the treatment effect of an ace inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease a combined analysis of individual data of advance europa and progress trials
European Heart Journal, 2009Co-Authors: Jasper J. Brugts, Willem J Remme, M E Bertrand, Stephen Macmahon, John Chalmers, Eric Boersma, Roberto Ferrari, Toshiharu Ninomiya, Maarten L. SimoonsAbstract:Aims Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of Perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. Methods and results We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a Perindopril-based treatment regimen or placebo. The Perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82–0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95% CI 0.76–0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95% CI 0.71–0.90; P < 0.001), stroke (HR 0.82; 95% CI 0.74–0.92; P = 0.002), and heart failure (HR 0.84; 95% CI 0.72–0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. Conclusion This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (Perindopril–indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.
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blood pressure lowering with fixed combination Perindopril indapamide key findings from advance
Journal of Hypertension, 2008Co-Authors: John Chalmers, Rohina Joshi, A P Kengne, Stephen MacmahonAbstract:OBJECTIVES ADVANCE was planned to investigate the effects of routine blood pressure lowering with the fixed combination Perindopril-indapamide on major vascular events in people with type 2 diabetes, irrespective of initial blood pressures or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors. METHODS A total of 11140 individuals with type 2 diabetes were randomly assigned to fixed combination Perindopril-indapamide or matching placebo, after a 6-week run-in period. The primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately, by intention to treat. RESULTS Active treatment reduced blood pressure by 5.6/2.2 mmHg compared with placebo and the relative risks of all deaths, cardiovascular deaths and major vascular events, by 14% (P = 0.025), 18% (P = 0.027) and 9% (P = 0.041), respectively. There were also reductions in total coronary events (14%; P = 0.02) and total renal events (21%; P < 0.0001). Study treatment was well tolerated, with 73% and 74% of participants who received active treatment and placebo, respectively, still adherent to randomized therapy after an average of 4.3 years of follow-up. CONCLUSIONS Routine treatment with the fixed combination Perindopril-indapamide, on top of all concomitant protective therapies, was well tolerated and reduced the risks of death and vascular disease irrespective of the initial level of blood pressure. The results suggest that for every 79 patients so treated, one death would be averted over 5 years.
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Perindopril based blood pressure lowering in individuals with cerebrovascular disease consistency of benefits by age sex and region
Journal of Hypertension, 2004Co-Authors: Anthony Rodgers, John Chalmers, Mark Woodward, Neil Chapman, Lisheng Liu, S Colman, Arier C Lee, Stephen MacmahonAbstract:ObjectiveTo assess the consistency of the benefits of blood pressure lowering on secondary stroke risk by age, sex and geographic region of recruitment.DesignRandomized, placebo-controlled trial. Participants were randomized to the angiotensin-converting enzyme (ACE) inhibitor Perindopril (plus the
Bruce Neal - One of the best experts on this subject based on the ideXlab platform.
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effects of blood pressure lowering on cardiovascular outcomes in different cardiovascular risk groups among participants with type 2 diabetes
Diabetes Research and Clinical Practice, 2012Co-Authors: John Chalmers, Mark E Cooper, Susan Van Dieren, Andre Pascal Kengne, Joline W J Beulens, Diederick E Grobbee, Stephen B Harrap, Giuseppe Mancia, Bruce NealAbstract:Abstract Aims To asses differences in treatment effects of a fixed combination of Perindopril–indapamide on major clinical outcomes in patients with type 2 diabetes across subgroups of cardiovascular risk. Methods 11,140 participants with type 2 diabetes, from the ADVANCE trial, were randomized to Perindopril–indapamide or matching placebo. The Framingham equation was used to calculate 5-year CVD risk and to divide participants into two risk groups, moderate–high risk ( 25% and/or history of macrovascular disease). Endpoints were macrovascular and microvascular events. Results The mean age of participants was 66 years (42.5% female). 1000 macrovascular and 916 microvascular events were recorded over follow-up of 4.3 years. Relative treatment effects were similar across risk groups, (all P -values for heterogeneity ≥0.38). Hazard ratios for combined macro- and microvascular events were 0.89 (0.77–1.03) for the moderate-high risk and 0.92 (0.81–1.03) for the very high risk. Absolute treatment effects tended to be greater in the high risk groups although differences were not statistically significant ( P >0.05). Conclusions Relative effects of blood pressure lowering with Perindopril–indapamide on cardiovascular outcomes were similar across risk groups whilst absolute effects trended to be greater in the high risk group.
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Perindopril based blood pressure lowering reduces major vascular events in asian and western participants with cerebrovascular disease the progress trial
Journal of Hypertension, 2010Co-Authors: Hisatomi Arima, Stephen Macmahon, Bruce Neal, Christophe Tzourio, Anthony Rodgers, Mark Woodward, Craig S Anderson, Lisheng Liu, Teruo Omae, John ChalmersAbstract:ObjectiveTo assess the benefits of blood pressure (BP) lowering on vascular events separately for Asian and for Western participants with particular emphasis on stroke subtypes and cardiac outcomes.MethodsThis is a subsidiary analysis of Perindopril Protection Against Recurrent Stroke Study (PROGRES
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chronic kidney disease cardiovascular events and the effects of Perindopril based blood pressure lowering data from the progress study
Journal of The American Society of Nephrology, 2007Co-Authors: Toshiharu Ninomiya, Vlado Perkovic, Hisatomi Arima, Martin Gallagher, Meg Jardine, Alan Cass, Bruce NealAbstract:Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease, but evidence regarding the effectiveness of interventions to reduce that risk is lacking. The Perindopril Protection against Recurrent Stroke Study (PROGRESS) study enrolled 6105 participants with cerebrovascular disease and randomly allocated them to Perindopril-based blood pressure–lowering therapy or placebo. Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events, stroke, and coronary heart disease, and were more than twice as likely to die (all P0.002). Perindopril-based treatment reduced the risk of major vascular events by 30% and stroke by 35% among subjects with CKD, and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without. Considering patients with CKD and a history of cerebrovascular disease, Perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years. In conclusion, kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease.
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effects of a Perindopril based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease
European Heart Journal, 2003Co-Authors: V Chaturvedi, Stephen Macmahon, John Chalmers, Bruce Neal, Anushka Patel, Neil Chapman, L Hansson, G Mancia, J Reid, N SharpeAbstract:Aim: To determine the effects of a Perindopril-based blood pressure lowering regimen on major cardiac events among hypertensive and non-hypertensive patients with a history of cerebrovascular disease. Methods and results: A total of 6105 individuals with a history of stroke or transient ischaemic attack were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised the angiotensin-converting-enzyme inhibitor Perindopril (4mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. Over a mean of 3.9 years of follow-up, active treatment reduced blood pressure by 9/4mmHg compared with placebo and reduced the primary outcome, stroke, by 28%. Major coronary events occurred in 269 participants (active 3.8%, placebo 5.0%) and heart failure was diagnosed in 264 participants (active 3.7%, placebo 4.9%). Active treatment reduced the risk of major coronary events by 26% (95% CI: 6–42%; p=0.02) and the risk of congestive heart failure by 26% (5–42%; p=0.02). For each of these outcomes, there was no clear evidence of differences between the treatment effects in participants classified as hypertensive or non-hypertensive, and those with or without a history of coronary heart disease. Conclusions: Among individuals with cerebrovascular disease, blood pressure lowering with a regimen involving Perindopril and indapamide not only reduced the risk of stroke, but also substantially reduced the risks of cardiac outcomes.
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randomised trial of a Perindopril based blood pressure lowering regimen among 6 105 individuals with previous stroke or transient ischaemic attack
The Lancet, 2001Co-Authors: Stephen Macmahon, John Chalmers, Bruce Neal, Christophe Tzourio, Anthony Rodgers, Mark Woodward, J A Cutler, Craig S Anderson, T OhkuboAbstract:Background Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease. However, there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients. The Perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack. Methods 6105 individuals from 172 centres in Asia, Australasia, and Europe were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised a flexible regimen based on the angiotensin-converting-enzyme inhibitor Perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. Findings Over 4 years of follow up, active treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo (relative risk reduction 28% [95% Cl 17-38], p<0.0001). Active treatment also reduced the risk of total major vascular events (26% [16-34]). There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (all p<0.01). Combination therapy with Perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke. Interpretation This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with Perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with Perindopril alone. Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack, irrespective of their blood pressure.
Maarten L. Simoons - One of the best experts on this subject based on the ideXlab platform.
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the treatment effect of an ace inhibitor based regimen with Perindopril in relation to beta blocker use in 29 463 patients with vascular disease a combined analysis of individual data of advance europa and progress trials
Cardiovascular Drugs and Therapy, 2017Co-Authors: Jasper J. Brugts, Willem J Remme, Stephen Macmahon, John Chalmers, Maarten L. Simoons, Roberto Ferrari, Michel E Bertrand, Keith Fox, Eric BoersmaAbstract:Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large Perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a Perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/Perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding Perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of Perindopril treatment are additive to the background beta-blockers use.
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the consistency of the treatment effect of an ace inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease a combined analysis of individual data of advance europa and progress trials
European Heart Journal, 2009Co-Authors: Jasper J. Brugts, Willem J Remme, M E Bertrand, Stephen Macmahon, John Chalmers, Eric Boersma, Roberto Ferrari, Toshiharu Ninomiya, Maarten L. SimoonsAbstract:Aims Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of Perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. Methods and results We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a Perindopril-based treatment regimen or placebo. The Perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82–0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95% CI 0.76–0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95% CI 0.71–0.90; P < 0.001), stroke (HR 0.82; 95% CI 0.74–0.92; P = 0.002), and heart failure (HR 0.84; 95% CI 0.72–0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. Conclusion This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (Perindopril–indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.
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the cardioprotective effects of the angiotensin converting enzyme inhibitor Perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency insights from the europa trial
Journal of the American College of Cardiology, 2007Co-Authors: Jasper J. Brugts, Willem J Remme, Eric Boersma, Roberto Ferrari, Jaap W Deckers, Michel E Bertrand, Kim Fox, Michel Chonchol, Maarten L. SimoonsAbstract:Objectives This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitor therapy by Perindopril are modified by renal function in patients with stable coronary artery disease. Background A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy. In light of the growing interest in tailored therapy for targeting medications to specific subgroups, remarks on the consistency of the treatment effect by ACE inhibitors are highly important. Methods The present study involved 12,056 patients with stable coronary artery disease without heart failure randomized to Perindopril or placebo. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Cox regression analysis was used to estimate multivariable-adjusted hazard ratios. Results The mean eGFR was 76.2 (±18.1) ml/min/1.73 m2. During follow-up, the primary end point (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761 patients (7.9%) with eGFR ≥75 and in 631 of 6,295 patients (10.0%) with eGFR Conclusions The treatment benefit of Perindopril is consistent and not modified by mild to moderate renal insufficiency.
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cost effectiveness of Perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the europa study
Heart, 2007Co-Authors: Andrew Briggs, Willem J Remme, Maarten L. Simoons, Roberto Ferrari, Jaap W Deckers, Borislava Mihaylova, Mark Sculpher, Alistair S Hall, Jane Wolstenholme, Michel E BertrandAbstract:Background: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. Objective: To assess the cost effectiveness of Perindopril in stable coronary heart disease in the UK. Methods: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. Results: The median incremental cost of Perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as £9700 (interquartile range £6400-£14 200). Overall, 88% of the EUROPA population had an estimated cost per QALY below £20 000 and 97% below £30 000. For a threshold value of cost effectiveness of £30 000 per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for Perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. Conclusions: Whether the use of Perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.
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long term effect of Perindopril on coronary atherosclerosis progression from the Perindopril s prospective effect on coronary atherosclerosis by angiography and intravascular ultrasound evaluation perspective study
American Journal of Cardiology, 2007Co-Authors: Gaston A Rodriguezgranillo, Maarten L. Simoons, Jeroen Vos, Nico Bruining, Hector M Garciagarcia, Sebastiaan De Winter, Jurgen Ligthart, Jaap W Deckers, Michel E Bertrand, Roberto FerrariAbstract:The multicenter EUROPA trial of 12,218 patients showed that Perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of Perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to Perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and β blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the Perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the Perindopril and placebo groups (minimum and mean luminal diameters −0.07 ± 0.4 vs −0.02 ± 0.4 mm, p = 0.34; mean luminal diameter −0.05 ± 0.2 vs −0.05 ± 0.3 mm, p = 0.89; mean plaque cross-sectional area −0.18 ± 1.2 vs −0.02 ± 1.2 mm2, p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of Perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.
Roberto Ferrari - One of the best experts on this subject based on the ideXlab platform.
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the treatment effect of an ace inhibitor based regimen with Perindopril in relation to beta blocker use in 29 463 patients with vascular disease a combined analysis of individual data of advance europa and progress trials
Cardiovascular Drugs and Therapy, 2017Co-Authors: Jasper J. Brugts, Willem J Remme, Stephen Macmahon, John Chalmers, Maarten L. Simoons, Roberto Ferrari, Michel E Bertrand, Keith Fox, Eric BoersmaAbstract:Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large Perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a Perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/Perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding Perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of Perindopril treatment are additive to the background beta-blockers use.
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the consistency of the treatment effect of an ace inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease a combined analysis of individual data of advance europa and progress trials
European Heart Journal, 2009Co-Authors: Jasper J. Brugts, Willem J Remme, M E Bertrand, Stephen Macmahon, John Chalmers, Eric Boersma, Roberto Ferrari, Toshiharu Ninomiya, Maarten L. SimoonsAbstract:Aims Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of Perindopril-based regimen in patients with vascular disease or at high risk of vascular disease. Methods and results We studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a Perindopril-based treatment regimen or placebo. The Perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82–0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95% CI 0.76–0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95% CI 0.71–0.90; P < 0.001), stroke (HR 0.82; 95% CI 0.74–0.92; P = 0.002), and heart failure (HR 0.84; 95% CI 0.72–0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure. Conclusion This study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (Perindopril–indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease.
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the cardioprotective effects of the angiotensin converting enzyme inhibitor Perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency insights from the europa trial
Journal of the American College of Cardiology, 2007Co-Authors: Jasper J. Brugts, Willem J Remme, Eric Boersma, Roberto Ferrari, Jaap W Deckers, Michel E Bertrand, Kim Fox, Michel Chonchol, Maarten L. SimoonsAbstract:Objectives This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitor therapy by Perindopril are modified by renal function in patients with stable coronary artery disease. Background A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy. In light of the growing interest in tailored therapy for targeting medications to specific subgroups, remarks on the consistency of the treatment effect by ACE inhibitors are highly important. Methods The present study involved 12,056 patients with stable coronary artery disease without heart failure randomized to Perindopril or placebo. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Cox regression analysis was used to estimate multivariable-adjusted hazard ratios. Results The mean eGFR was 76.2 (±18.1) ml/min/1.73 m2. During follow-up, the primary end point (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761 patients (7.9%) with eGFR ≥75 and in 631 of 6,295 patients (10.0%) with eGFR Conclusions The treatment benefit of Perindopril is consistent and not modified by mild to moderate renal insufficiency.
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cost effectiveness of Perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the europa study
Heart, 2007Co-Authors: Andrew Briggs, Willem J Remme, Maarten L. Simoons, Roberto Ferrari, Jaap W Deckers, Borislava Mihaylova, Mark Sculpher, Alistair S Hall, Jane Wolstenholme, Michel E BertrandAbstract:Background: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. Objective: To assess the cost effectiveness of Perindopril in stable coronary heart disease in the UK. Methods: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. Results: The median incremental cost of Perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as £9700 (interquartile range £6400-£14 200). Overall, 88% of the EUROPA population had an estimated cost per QALY below £20 000 and 97% below £30 000. For a threshold value of cost effectiveness of £30 000 per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for Perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. Conclusions: Whether the use of Perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.
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long term effect of Perindopril on coronary atherosclerosis progression from the Perindopril s prospective effect on coronary atherosclerosis by angiography and intravascular ultrasound evaluation perspective study
American Journal of Cardiology, 2007Co-Authors: Gaston A Rodriguezgranillo, Maarten L. Simoons, Jeroen Vos, Nico Bruining, Hector M Garciagarcia, Sebastiaan De Winter, Jurgen Ligthart, Jaap W Deckers, Michel E Bertrand, Roberto FerrariAbstract:The multicenter EUROPA trial of 12,218 patients showed that Perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of Perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to Perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and β blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the Perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the Perindopril and placebo groups (minimum and mean luminal diameters −0.07 ± 0.4 vs −0.02 ± 0.4 mm, p = 0.34; mean luminal diameter −0.05 ± 0.2 vs −0.05 ± 0.3 mm, p = 0.89; mean plaque cross-sectional area −0.18 ± 1.2 vs −0.02 ± 1.2 mm2, p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of Perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.
