Perindopril-based Blood Pressure Lowering Regimen Research Articles

An economic evaluation of a perindopril-based blood pressure lowering regimen for patients who have suffered a cerebrovascular event

Cerebrovascular disease (or stroke) is one of the main causes of long-term disability and the second leading cause of death worldwide. The economic impact of stroke is clearly seen, as it is the largest single cause of bed occupancy in hospitals in England and accounts for 6% of hospital costs. This analysis is the first to quantify the economic consequences of a blood pressure lowering regimen based on the PROGRESS study (perindopril-based regimen), for reducing future cardiovascular events. A Markov decision analytical model was used to estimate the cost per quality adjusted life year (QALY) of blood pressure lowering in the treatment of patients presenting with a cerebrovascular event. The health states are based upon Barthel indices for which resource utilisation and health benefits have previously been estimated. The participants for the economic analysis were obtained from the PROGRESS study database. 6,105 clinical study participants were recruited through both primary and secondary care centres. The mean age was 64 years; 70% were male in the original study. In the PROGRESS study, blood pressure lowering by a perindopril-based regimen was compared to standard care. Cost per quality adjusted life year for the duration of the study (4 years) and for a time span of 20 years. Using only direct hospital medical costs, the cost per QALY for a perindopril based regimen is pound 6,927 for the base study period and pound 10,133 for a 20-year time period. These results are sensitive to the cost of perindopril, the cost of the stroke unit, length of stay, and to a lesser extent, the cost of indapamide. This analysis demonstrates a cost-effective treatment for patients suffering a cerebrovascular event with a blood pressure lowering regimen. The findings of this study are in line with current decisions and guidance by the national institute for health and clinical excellence (NICE) in England.

Prediction of Myocardial Infarction by N-Terminal-Pro-B-Type Natriuretic Peptide, C-Reactive Protein, and Renin in Subjects With Cerebrovascular Disease

B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited. N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood samples from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI; the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT-proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin. NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for all other predictors, including LDL and HDL cholesterol levels. Individuals with both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI compared with subjects with both biological markers in their lowest quarters. NT-proBNP and renin, but not CRP, are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.

N-Terminal-Pro-B–Type Natriuretic Peptide

Plasma brain-type natriuretic peptide (BNP) and amino-terminal proBNP (NTproBNP) provide prognostic information on cardiovascular morbidity and mortality beyond that provided by standard risk factors. Clinical applications of B-type peptides under ongoing research include their use in diagnosing acute heart failure (HF), in risk stratification in both acute and established HF, in acute coronary syndromes (ACS), in asymptomatic populations at cardiovascular risk (older adults and people with hypertension), and as part of a screening strategy for detection of left ventricular impairment and prediction of cardiovascular risk in the general population.1,2 In this issue of Circulation , Campbell and colleagues3 assess the ability of NTproBNP to predict myocardial infarction (MI) in subjects who have experienced a cerebrovascular event. NTproBNP (reflecting cardiac distension) is compared with C-reactive protein (a systemic marker of inflammation) and renin (a marker of sodium status regulated by renal perfusion and delivery of sodium to the renal glomerulus). See p 110 The nested case-control study is from the 6105 participants in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of converting enzyme inhibitor–based therapy in patients with previous cerebrovascular events.4 Within PROGRESS, 206 subjects incurred an MI during 3.9 years of follow-up. The investigators matched those incurring an MI with control PROGRESS patients avoiding MI from time of randomization to time of case ascertainment. Cases and controls were matched for age, gender, treatment allocation, region, and cerebrovascular qualifying event. The form of matching meant that individual patients may have been controls initially and subsequently became cases on incurring an MI during further follow-up. Matching in this fashion may confuse the interpretation of the nonconditioned analysis of baseline variables. Comparing the 206 cases with 412 controls at randomization, the investigators report that in addition to higher systolic blood pressure, more frequent known coronary disease, …

Critical Care and Emergency Medicine Neurology in Stroke

Dramatic changes have occurred in the area of critical care and emergency stroke treatments of intracerebral hemorrhage (ICH). New data from three sponsored clinical trials: STICH (British National Health System-Medical Research Council), NOVO Seven (Novonordisk), and intraventricular hemorrhage (IVH) clot lysis (FDA Orphan Drug Program)1 were presented at the 29th International Stroke Meeting2 and the World Stroke Congress. Several avenues of approach to the problem of ICH are opening. Although the data from these trials are now under peer review, the initial presentations have demonstrated several principles that seem clear. First, craniotomy (though not better than initial medical management) is safe and not worse than initial medical management. Second, deterioration occurs frequently (≈25% of the time) in the initial days after ICH. Deterioration was treated with surgery. Third, a strategy of emergent clot stabilization is safe and shows trends toward efficacy in the NOVO Seven dose finding study.2 Finally, catheter-assisted removal of blood clot from the obstructed ventricular system in IVH can be accomplished safely with low dose recombinant tissue plasminogen activator (rtPA).3 These trial results suggest that the basic elements of aneurysm care are now being applied to ICH care: emergent stabilization of the bleeding site, followed by removal of blood and management of cranial vault mechanics. Data are now beginning to support that applying these principles leads to improvement in mortality and morbidity. We hope that the robustness of the peer-reviewed data continues to point to the value of emergent intervention for the ICH patient. New sponsored trials have already started: CLEAR IVH, a phase IIb dose optimization trial directed at finding the best dose of rtPA to rapidly remove blood from the ventricles (FDA Orphan drug program)4; MISTIE, an NIH sponsored phase II safety study of minimally invasive surgery plus …

Angiotensin-Converting Enzyme Inhibitors and Diuretics: Optimal Combination Therapy

Letters7 December 2004Angiotensin-Converting Enzyme Inhibitors and Diuretics: Optimal Combination TherapyBarry R. Davis, MD, PhD, Curt D. Furberg, MD, PhD, Jackson T. Wright Jr., MD, PhD, Jeffrey A. Cutler, MD, MPH, and Paul Whelton, MD, MScBarry R. Davis, MD, PhDFrom The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112.Search for more papers by this author, Curt D. Furberg, MD, PhDFrom The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112.Search for more papers by this author, Jackson T. Wright Jr., MD, PhDFrom The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112.Search for more papers by this author, Jeffrey A. Cutler, MD, MPHFrom The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112.Search for more papers by this author, and Paul Whelton, MD, MScFrom The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-11-200412070-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Krantz for his thoughtful letter. The proposed strategy of using a diuretic and an ACE inhibitor simultaneously is supported by the effects of combined treatment in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) (1). However, that study could also be (and was) interpreted as showing that it's the blood pressure that matters, especially for stroke, and blood pressure reduction is much more effective with a diuretic in the regimen. Although the use of ACE inhibitors could in theory offset the metabolic effects (higher glucose and lower potassium levels) of thiazides, other potassium-sparing regimens may ...Reference1. Chapman N, Huxley R, Anderson C, Bousser MG, Chalmers J, Colman S, et al. Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial. Stroke. 2004;35:116-21. [PMID: 14671247] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From The University of Texas School of Public Health at Houston, Houston, TX 77030; Wake Forest University School of Medicine, Winston-Salem, NC 27157; Case Western Reserve University, Cleveland, OH 44106; National Heart, Lung, and Blood Institute, Bethesda, MD 20892; and Tulane University Health Sciences Center, New Orleans, LA 70112. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoALLHAT: Setting the Record Straight Barry R. Davis , Curt D. Furberg , Jackson T. Wright Jr. , Jeffrey A. Cutler , Paul Whelton , and Angiotensin-Converting Enzyme Inhibitors and Diuretics: Optimal Combination Therapy Mori J. Krantz and Philip S. Mehler Metrics 7 December 2004Volume 141, Issue 11Page: 893KeywordsACE inhibitorsBlood pressureDiureticsDrugsEnzyme replacement therapyGlucoseHeart failurePotassiumRandomized trialsStroke ePublished: 7 December 2004 Issue Published: 7 December 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Prediction of Heart Failure by Amino Terminal-pro–B-Type Natriuretic Peptide and C-Reactive Protein in Subjects With Cerebrovascular Disease

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.

Effects of a perindopril-based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease

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. 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 (4 mg 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 9/4 mm Hg 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. 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.

Randomized trial of perindopril-based blood pressure lowering regimen among 6105 individuals with previous stroke or transient ischemic attack

Randomized trial of perindopril-based blood pressure lowering regimen among 6105 individuals with previous stroke or transient ischemic attack