Current status: heart rate as a treatable risk factor

Resting heart is an independent predictor of all-cause mortality and cardiovascular mortality. In patients with coronary artery disease and left ventricular dysfunction, the morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) trial showed that a heart rate of 70 b.p.m. or greater is an independent predictor of cardiovascular events. In patients with moderate-to-severe heart failure, the SHIFT (Systolic Heart failure treatment with the If inhibitor Trial) showed also that heart rate was a predictor of cardiovascular death and heart failure hospitalisation. Heart rate plays an important role in the pathophysiology of atherosclerosis. The BEAUTIFUL trial and SHIFT provide evidence for the benefits of heart rate reduction using the new heart rate-lowering agent ivabradine, even in patients on beta-blockers. The BEAUTIFUL trial showed that in patients with a heart rate of 70 b.p.m. or more, ivabradine significantly reduced hospitalisation for fatal and non-fatal myocardial infarction or hospitalisation for heart failure and coronary revascularisation. In the SHIFT, heart rate reduction with ivabradine improved clinical outcomes. Therefore, high heart rate represents an important risk factor the effects of which can be reversed by ivabradine in patients with coronary artery disease or heart failure with or without background beta-blocker therapy.

[1]  Michael Böhm,et al.  Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study , 2010, The Lancet.

[2]  Michael Böhm,et al.  Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial , 2010, The Lancet.

[3]  P. Ponikowski,et al.  Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial , 2009, European heart journal.

[4]  R. Ferrari,et al.  Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial , 2008, The Lancet.

[5]  R. Ferrari,et al.  Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial , 2008, The Lancet.

[6]  C. Pepine,et al.  Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST). , 2007, European heart journal.

[7]  M. Cucherat.  Quantitative relationship between resting heart rate reduction and magnitude of clinical benefits in post-myocardial infarction: a meta-regression of randomized clinical trials. , 2007, European heart journal.

[8]  Jean-Claude Tardif,et al.  Resting heart rate in cardiovascular disease. , 2007, Journal of the American College of Cardiology.

[9]  Deepak L. Bhatt,et al.  One-year cardiovascular event rates in outpatients with atherothrombosis. , 2007, JAMA.

[10]  C. Mathers,et al.  Projections of Global Mortality and Burden of Disease from 2002 to 2030 , 2006, PLoS medicine.

[11]  G. Mancia,et al.  Guidelines on the management of stable angina pectoris: executive summary: the task force on the management of stable angina pectoris of the European society of cardiology. , 2006, European heart journal.

[12]  S. Lévy,et al.  La fréquence cardiaque, facteur pronostique majeur du risque cardiovasculaire , 2006 .

[13]  Jean-Claude Tardif,et al.  Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. , 2005, European heart journal.

[14]  Jean-Claude Tardif,et al.  Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. , 2005, European heart journal.

[15]  Paolo Palatini,et al.  Heart rate: a strong predictor of mortality in subjects with coronary artery disease. , 2005, European heart journal.

[16]  F. Lallemand,et al.  Long-Term Heart Rate Reduction Induced by the Selective If Current Inhibitor Ivabradine Improves Left Ventricular Function and Intrinsic Myocardial Structure in Congestive Heart Failure , 2004, Circulation.

[17]  J. Borer,et al.  Antianginal and Antiischemic Effects of Ivabradine, an If Inhibitor, in Stable Angina: A Randomized, Double-Blind, Multicentered, Placebo-Controlled Trial , 2003, Circulation.

[18]  Victor F. Froelicher,et al.  Exercise capacity and mortality among men referred for exercise testing. , 2002, The New England journal of medicine.

[19]  S. Giampaoli,et al.  Heart rate as a predictor of mortality: the MATISS project. , 2001, American journal of public health.

[20]  C Guérot,et al.  Resting heart rate as a predictive risk factor for sudden death in middle-aged men. , 2001, Cardiovascular research.

[21]  A. Mallet,et al.  Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial , 2001, Circulation.

[22]  Daniel Levy,et al.  Lifetime risk of developing coronary heart disease , 1999, The Lancet.

[23]  A. Maggioni,et al.  Relevance of heart rate as a prognostic factor in patients with acute myocardial infarction: insights from the GISSI-2 study. , 1998, European heart journal.

[24]  A. Folsom,et al.  Recent trends in acute coronary heart disease--mortality, morbidity, medical care, and risk factors. The Minnesota Heart Survey Investigators. , 1996, The New England journal of medicine.

[25]  U. Goldbourt,et al.  The predictive value of admission heart rate on mortality in patients with acute myocardial infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial. , 1995, Journal of clinical epidemiology.

[26]  R B D'Agostino,et al.  Influence of heart rate on mortality among persons with hypertension: the Framingham Study. , 1993, American heart journal.

[27]  J Ross,et al.  Influence of heart rate on mortality after acute myocardial infarction. , 1990, The American journal of cardiology.

[28]  R S Paffenbarger,et al.  Heart rate and cardiovascular mortality: the Framingham Study. , 1987, American heart journal.

[29]  J. Kjekshus,et al.  Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. , 1986, The American journal of cardiology.

[30]  H A Lindberg,et al.  Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. , 1980, American journal of epidemiology.

[31]  K. Fox,et al.  Long-term beta blockade: possible protection from myocardial infarction. , 1975, British medical journal.

[32]  Dario DiFrancesco,et al.  Heart Rate Lowering by Specific and Selective If Current Inhibition with Ivabradine , 2012, Drugs.

[33]  P. Palatini.  Heart Rate as an Independent Risk Factor for Cardiovascular Disease , 2012, Drugs.

[34]  A. Poli.  Atorvastatin , 2012, Drugs.

[35]  L Guize,et al.  Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. , 1999, Hypertension.