Hypertension

Preventing vascular events due to elevated blood pressure.

Bood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system

Risk estimation and the prevention of cardiovascular disease - A national clinical Guideline.

Perindopril versus Angiotensin II Receptor Blockade in Hypertension and Coronary Artery Disease:

Clarifying the Role of ACE Inhibition in the Reduction of Cardiovascular Events in Patients with Hypertension

Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study

Brachial Pressure-Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives

Stable Coronary Heart Disease

Effects of perindopril on long-term clinical outcome of patients with coronary artery disease and preserved left ventricular function

Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials

Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?

AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update.

Treatment benefit by perindopril in patients with stable coronary artery disease at different levels of risk.

Heart Failure

Trends in prevalence and outcome of heart failure with preserved ejection fraction

Outcome of heart failure with preserved ejection fraction in a population-based study

Prior Events Predict Cerebrovascular and Coronary Outcomes in the PROGRESS Trial

Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack:

Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy.

Perindopril-Based Blood Pressure-lowering Reduces Major Vascular Events in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack.

HYPERTENSION

Preventing vascular events due to elevated blood pressure.
Circulation. 2006 May 9;113(18):2166-8.
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Salim Yusuf expressed his opinion on his preferred antihypertensive treatment in regards to hypertensive patient's needs: ACEi+CCB or ACEi+Diuretic.

Bood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system
Blood Pressure Lowering Treatment Trialists' Collaboration.
J Hypertens. 2007;25:951-958
Abstract

Objectives were to evaluate the blood pressure-dependent and independent effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on major cardiovascular events, using data from 26 large-scale trials comparing an ACEI or an ARB.

From a total of 146 838 individuals with high blood pressure or an elevated risk of cardiovascular disease, 22 666 major cardiovascular events were documented during follow-up.

Analyses also showed that ACEI produced a blood pressure-independent reduction in the relative risk of CHD of approximately 9%. No similar effect was detected for ARB, and there was some evidence of a difference between ACEI and ARB in this regard (P=0.002).

These analyses have identified a potentially important blood pressure-independent protective effect of ACEI on the risk of CHD. In particular, there was clear evidence of protection against coronary artery disease with ACEI even in the absence of any reduction in blood pressure.

These findings, therefore, suggest that the coronary disease prevention afforded by a blood pressure-lowering regimen may be determined by the choice of agent as well as the size of the blood pressure reduction achieved. Maximization of the benefit may therefore be achieved with a regimen that includes an ACEI together with other drugs.

There are similar blood pressure-dependent effects of ACEI and ARB for the risks of stroke, CHD and heart failure.

For ACEI, but no for ARB, there is evidence of blood pressure-independent effects on the risk of major coronary disease events.

Risk estimation and the prevention of cardiovascular disease - A national clinical Guideline.
Scottish Intercollegiate Guidelines Network (SIGN). 2007;97:40.
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In its new 2007 recommendations in the treatment of hypertensive patients, the new Scottish guidelines gives a large part to ASCOT trial and recommend the new A/BC algorithm:

The ASCOT-BPLA study recruited 19,257 patients, including many from Scotland, to treatment by two combinations of antihypertensive drugs. The study tested whether a newer antihypertensive combination treatment, comprising the calcium channel blocker (CCB) amlodipine and the ACE inhibitor perindopril, was more effective than an older combination regimen of the beta-blocker atenolol and the diuretic bendroflumethiazide. The trial was terminated early because of a large difference in mortality between the older drugs and the newer ones, favouring the amlodipine +perindopril combination. The trial showed that amlodipine+perindopril were significantly more effective at reducing strokes (327 vs 422; unadjusted hazard ratio (HR) 0.77, 95% CI 0.66 to 0.89, P<0.0003), total cardiovascular events (1362 vs 1602; HR 0.84, 95% CI 0.78 to 0.90, P<0.0001) and all cause mortality (738 vs 820; HR 0.89, 95% CI to 0.99, P=0.025) than atenolol with bendroflumethiazide.

Beta blockers are not a preferred initial therapy for hypertension but are an alternative to ACE inhibitors in patients < 55 years in whom ACE inhibitors or ARBs are not tolerated, or contraindicated (includes women of childbearing potential). Black patients are only those of African or Caribbean descent. In the absence of evidence, all other patients should be treated according to the algorithm as non-black.

Perindopril versus Angiotensin II Receptor Blockade in Hypertension and Coronary Artery Disease:
Implications of Clinical Trials.
Brady AJ.
Clin Drug Investig. 2007;27(3):149-61.
Abstract

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathogenesis of hypertension. Two groups of drugs, the ACE inhibitors and the angiotensin II type 1 receptor antagonists, aim to improve clinical outcomes.

The initial assumptions were that these two classes of drugs might be interchangeable, but ongoing research has revealed differences between them in terms of outcomes in clinical trials: further, recent debate has focused in particular on the incidence of myocardial infarction (MI) in patients receiving ARBS.

By regulation of the RAAS over 24 hours, perindopril has revealed beneficial effects on vascular and endothelial walls mediated by bradykinin and NO and in correlation with a decrease in blood pressure. Perindopril has demonstrated reduction in cardiovascular outcome in five different morbidity trials, with patients ranging from everyday hypertensive patients to patients with heart failure.

Clarifying the Role of ACE Inhibition in the Reduction of Cardiovascular Events in Patients with Hypertension
Philippe Meurin
Am J Cardiovasc Drugs 2006; 6 (5): 327-334
Abstract

The ASCOT-BPLA trial underlines the cardiovascular benefit of ACE inhibitors, specifically perindopril, beyond that provided by BP reduction, and potentially reflects a mechanistic feature of the ACE inhibitors. It also suggests that the combination of amlodipine plus perindopril may provide broad-spectrum cardiovascular protection, as well as reduce the incidence of new-onset diabetes mellitus and renal impairment, in addition to its efficacy in lowering BP. The ASCOT-BPLA trial provides evidence of the need to reconsider traditional prescribing recommendations in patients with hypertension, particularly conclusions reached in the US after the publication of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study. The recently published National Institute for Health and Clinical Excellence (NICE) guidelines in the UK emphasize the efficacy of ACE inhibitors as first-line agents for hypertensive patients <55 years of age and recommend ACE inhibitor therapy at any stage of hypertension management.

Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study
Daniel G Hackam, Deva Thiruchelvam, Donald A Redelmeier
Lancet. 2006;368:659-665.
Abstract

ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

Brachial Pressure-Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives
Anne-Isabelle Tropeano, Pierre Boutouyrie, Bruno Pannier, Robinson Joannides, Elisabeth Balkestein, Sandrine Katsahian, Brigitte Laloux, Christian Thuillez, Harry Struijker-Boudier, Stéphane Laurent
Hypertension. 2006 May 15; [Epub ahead of print]
Abstract

These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with Coversyl. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of doses of 8 mg of Coversyl improves carotid structure and function in hypertensive patients with type 2 diabetes.

STABLE CORONARY HEART DISEASE

Effects of perindopril on long-term clinical outcome of patients with coronary artery disease and preserved left ventricular function
Bertrand ME, Remme WJ, Fox KM, Ferrari R, Simoons ML; On behalf of the EUROPA investigators.
Int J Cardiol. 2007 Jan 30; [Epub ahead of print].
Abstract

The EUROPA trial has demonstrated that an ACE inhibitor perindopril was able to significantly decrease the risk of major cardiac events in patients with stable coronary heart disease without apparent heart failure.

To assess the long-term clinical outcome of patients with stable coronary heart disease and preserved left ventricular function, a retroprospective evaluation of LVEF was performed in the EUROPA study population.

LVEF was documented in 58% of the EUROPA study population and only 3% had an impaired LV function.

The baseline characteristics of patients with documented LVEF were similar to the whole EUROPA population.

In patients (n=6878) with documented preserved LV function (LVEF = 40%), there was a significant relative risk reduction of 16% of the primary endpoint (a composite of cardiovascular death, non-fatal myocardial infarction and resuscitated cardiac arrest) in the group treated with perindopril 8 mg (8.3%) in comparison to the group treated with placebo (9.8%).

Results in patients with documented preserved LV function are consistent with those of the whole EUROPA study population and perindopril 8 mg is beneficial in the broad spectrum of patients with stable coronary artery disease without evidence of heart failure.

Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials
Gilles R Dagenais, Janice Pogue, Kim Fox, Marteen L Simoons, Salim Yusuf
Lancet. 2006 Aug 12;368(9535):581-8.
Abstract

Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?
Kim Fox, Roberto Ferrari , Salim Yusuf , and Jeffrey S. Borer
Eur Heart J. 2006 Aug 11; [Epub ahead of print]
Abstract

ACE inhibitors reduce serious vascular events in patients with atherosclerosis without known evidence of LVSD or heart failure. Results showing these benefi ts in intermediate-risk patients complement existing evidence of similar benefi t in higher-risk patients with LVSD or heart failure. Therefore, use of ACE inhibitors should be considered in all patients with atherosclerosis.

AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update.
Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA.
Circulation. 2006;113:2363-2372.
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Since the 2001 update of the American Heart Association (AHA)/American College of Cardiology (ACC) consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports and broadens the merits of aggressive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease, and carotid artery disease.

AHA/ACC 2006 Guidelines recommend ACE inhibitors as first line antihypertensive in coronary patients with blood pressure superior to 140/90, or blood pressure superior to 130/90 in patients with diabetes or chronic kidney disease. (Level IA).

In Coronary patients, ACE inhibitors should be started and continued indefinitely in all patients with hypertension, left ventricular ejection fraction inferior to 40%, diabetes and chronic kidney disease (Level IA).

ACE inhibitors should also be considered for all other patients (Level IB).

Treatment benefit by perindopril in patients with stable coronary artery disease at different levels of risk.
Deckers JW, Goedhart DM, Boersma E, Briggs A, Bertrand M, Ferrari R, Remme WJ, Fox K, Simoons ML.
Eur Heart J. 2006 Apr;27(7):796-801. Epub 2006 Feb 23.
Abstract

Patients with stable coronary artery disease (CAD) are at increased risk. We developed a cardiovascular risk model based on the EUROPA study population and investigated whether benefit of long-term administration of the angiotensin-converting enzyme (ACE)-inhibitor perindopril was modified by risk level.

HEART FAILURE

Trends in prevalence and outcome of heart failure with preserved ejection fraction
Theophillus E. Owan, MD; David O. Hodge, MS; Regina M. Herges, BS; Steven J. Jacobsen, MD, PhD; Veronique L. Roger, MD, MPH; Margaret M. Redfield, MD.
N Engl J Med. 2006 July 20;355:251-9.
Abstract

The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period.

Secular trends in the type of heart failure, associated cardiovascular disease, and survival were defined.

Outcome of heart failure with preserved ejection fraction in a population-based study
R. Sacha Bhatia, MD, MBA; Jack V. Tu, MD, PhD; Douglas S. Lee, MD, PhD; Peter C. Austin, PhD; Jiming Fang, PhD; Annick Haouzi, MD; Yanyan Gong, MSc; Peter P. Liu, MD.
N Engl J Med. 2006 July 20;355:260-9.
Abstract

The importance of heart failure with preserved ejection fraction is increaingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduce ejection fraction.

The main outcome measures were death within one year and readmission to the hospital for heart failure.

CEREBROVASCULAR DISEASE

Prior Events Predict Cerebrovascular and Coronary Outcomes in the PROGRESS Trial
Hisatomi Arima, MD; Christophe Tzourio, MD; Ken Butcher, MD; Craig Anderson, MD; Marie-Germaine Bousser, MD; Kennedy R. Lees, MD; John L. Reid, DM; Teruo Omae, MD; Mark Woodward, PhD; Stephen MacMahon, PhD; John Chalmers, MD for the PROGRESS Collaborative Group
Stroke. 2006 Jun;37(6):1497-502. Epub 2006 Apr 20.
Abstract

Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP-lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.

Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack:
A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke

Co-Sponsored by the Council on Cardiovascular Radiology and Intervention The American Academy of Neurology affirms the value of this guideline.

Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T; American Heart Association/American Stroke Association Council on Stroke; Council on Cardiovascular Radiology and Intervention; American Academy of Neurology.
Circulation. 2006 Mar 14;113(10):e409-49.
Abstract

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack

Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy.
Dufouil C, Chalmers J, Coskun O, Besancon V, Bousser MG, Guillon P, MacMahon S, Mazoyer B, Neal B, Woodward M, Tzourio-Mazoyer N, Tzourio C; PROGRESS MRI Substudy Investigators.
Circulation. 2005 Sep 13;112(11):1525-6.
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In patients with cerebrovascular disease Coversyl-based blood pressure-lowering regimen limits progression of white matter hyperitensities. The later include areas of demyelination and silent infarcts observed in brain when using Magnetic Resonance Imaging and are associated with cognitive impairment or dementia, depression, and gait disturbances

Perindopril-Based Blood Pressure-lowering Reduces Major Vascular Events in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack.
Arima H, Hart RG, Colman S, Chalmers J, Anderson C, Rodgers A, Woodward M, Macmahon S, Neal B.
Stroke 2005;36:2164.
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In patients with cerebrovascular disease and atrial fibrillation Coversyl-based therapy significantly reduces major vascular events by 38% and stroke by 34%. This effect is irrespective of anticoagulant therapy and presence of hypertension.