Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)

Background— Hypertension treatment guidelines recommend that blood pressure (BP) be lowered to <140/90 mm Hg, but that a reduction to <130/80 mm Hg be adopted in patients at high cardiovascular (CV) risk. We investigated the CV and renal benefits associated with these BP targets in the high-CV-risk population of the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Methods and Results— Patients were divided into 4 groups according to the proportion of in-treatment visits before the occurrence of an event (<25%–>75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for demographic and clinical variables, a progressive increase in the proportion of visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a progressive reduction in the risk of stroke, new onset of microalbuminuria or macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An increased frequency of BP control to either target did not have any consistent effect on the adjusted risk of myocardial infarction and heart failure. The adjusted risk of CV events was reduced by increasing the frequency of BP control to <140/90 mm Hg, but not to <130/80 mm Hg. Similar findings were obtained for the achievement of the BP target in the visit preceding a CV event. Conclusion— The more frequent achievement of the BP targets recommended by guidelines led to cerebrovascular and renal protection, but did not increase cardiac protection. Overall, CV protection was favorably affected by the less tight but not by the tighter BP target. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

[1]  G. Bakris,et al.  Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. , 2010, JAMA.

[2]  Kevin A Peterson,et al.  Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus , 2011 .

[3]  P. Rothwell,et al.  Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis , 2010, The Lancet.

[4]  E. O’Brien,et al.  Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension , 2010, The Lancet.

[5]  W. Elliott Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document , 2010 .

[6]  Mark Woodward,et al.  Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. , 2009, Journal of the American Society of Nephrology : JASN.

[7]  S. Yusuf,et al.  Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study , 2009, Journal of hypertension.

[8]  G. Mancia,et al.  When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisal , 2009, Journal of hypertension.

[9]  C. Tsioufis,et al.  Left ventricular hypertrophy versus chronic kidney disease as predictors of cardiovascular events in hypertension: a Greek 6-year-follow-up study , 2009, Journal of hypertension.

[10]  M. Woodward,et al.  Lowering blood pressure reduces renal events in type 2 diabetes. , 2009, Journal of the American Society of Nephrology : JASN.

[11]  Giuseppe Mancia,et al.  Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document , 2009, Blood pressure.

[12]  S. Yusuf,et al.  Telmisartan, ramipril, or both in patients at high risk for vascular events. , 2008, The New England journal of medicine.

[13]  G. Mancia,et al.  Blood Pressure Control and Improved Cardiovascular Outcomes in the International Verapamil SR-Trandolapril Study , 2007, Hypertension.

[14]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[15]  M. Pfeffer,et al.  Blood pressure-dependent and independent effects of agents that inhibit the renin–angiotensin system , 2007, Journal of hypertension.

[16]  S. Grundy,et al.  Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus , 2006, Diabetes Care.

[17]  Peter Lindgren,et al.  Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary , 2007 .

[18]  M. Laakso,et al.  Guidelines on Diabetes, Pre-Diabetes, and Cardiovascular Diseases: Executive Summary , 2007 .

[19]  T. Burke,et al.  The Epidemiology of Stroke in the East Asian Region: A Literature-Based Review , 2006, International journal of stroke : official journal of the International Stroke Society.

[20]  G. Mancia,et al.  Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? , 2006, Annals of Internal Medicine.

[21]  M. Woodward,et al.  Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial , 2006, Journal of hypertension.

[22]  P. Okin,et al.  Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE Study , 2006, Journal of hypertension.

[23]  W. Zidek,et al.  Microalbuminuria and tubular proteinuria as risk predictors of cardiovascular morbidity and mortality in essential hypertension: final results of a prospective long-term study (MARPLE Study)* , 2006, Journal of Hypertension.

[24]  B. Brenner,et al.  Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy , 2004, Circulation.

[25]  Shah Ebrahim,et al.  European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. , 2004, European heart journal.

[26]  F. Turnbull Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials , 2003, The Lancet.

[27]  Shah Ebrahim,et al.  European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. , 2003 .

[28]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.

[29]  H. Hense,et al.  Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. , 2003, JAMA.

[30]  S. Lewington Prospective studies collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies (vol 360, pg 1903, 2002) , 2003 .

[31]  R. Collins,et al.  Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies , 2002, The Lancet.

[32]  G. Mancia,et al.  Systolic and diastolic blood pressure control in antihypertensive drug trials. , 2002, Journal of hypertension.

[33]  Jan A Staessen,et al.  Cardiovascular protection and blood pressure reduction: a meta-analysis , 2001, The Lancet.

[34]  M. Woodward,et al.  Randomised trial of a perindopril-based blood pressure lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack , 2001 .

[35]  D. Johnston Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack , 2001, The Lancet.

[36]  G. Bakris,et al.  Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[37]  L. Bouter,et al.  Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: five-year follow-up of the Hoorn Study. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[38]  Pats,et al.  Post-stroke antihypertensive treatment study. A preliminary result. , 1995, Chinese medical journal.

[39]  M. Guazzi,et al.  Upward Shift of the Lower Range of Coronary Flow Autoregulation in Hypertensive Patients With Hypertrophy of the Left Ventricle , 1991, Circulation.

[40]  O. Paulson,et al.  Cerebral blood flow in patients with congestive heart failure treated with captopril. , 1984, The American journal of medicine.

[41]  M. Gordon The renal circulation. , 1951, Canadian journal of medical technology.