Expert consensus document: A 'diamond' approach to personalized treatment of angina

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Abstract

A range of drugs is available for symptomatic angina, but the optimal choice or combination of therapies is often uncertain, and contemporary guidelines do not necessarily provide definite recommendations. In this Consensus Statement, Ferrari and colleagues propose an individualized approach to angina treatment, which takes into consideration the patient, their comorbidities, and the underlying mechanism of disease.

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Most cited references 68

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Coronary microvascular dysfunction: an update.

Filippo Crea, Paolo Camici, Cathleen Bairey Merz (2014)

Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy.

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Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

Kim Fox, Ian Ford, P Gabriel Steg … (2008)

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

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Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.

William J Elliott, Peter Meyer (2007)

The effect of different classes of antihypertensive drugs on incident diabetes mellitus is controversial because traditional meta-analyses are hindered by heterogeneity across trials and the absence of trials comparing angiotensin-converting-enzyme (ACE) inhibitors with angiotensin-receptor blockers (ARB). We therefore undertook a network meta-analysis, which accounts for both direct and indirect comparisons to assess the effects of antihypertensive agents on incident diabetes. We undertook a systematic review up to Sept 15, 2006, and identified 48 randomised groups of 22 clinical trials with 143,153 participants who did not have diabetes at randomisation and so were eligible for inclusion in our analysis. 17 trials enrolled patients with hypertension, three enrolled high-risk patients, and one enrolled those with heart failure. The main outcome was the proportion of patients who developed diabetes. Initial drug therapy used in the trials (and the number of patients with diabetes of the total number at risk) included: an ARB (1189 of 14,185, or 8.38%), ACE inhibitor (1618 of 22,941, or 7.05%), calcium-channel blocker (CCB, 2791 of 38,607, or 7.23%), placebo (1686 of 24,767, or 6.81%), beta blocker (2705 of 35,745, or 7.57%), or diuretic (998 of 18,699, or 5.34%). With an initial diuretic as the standard of comparison (eight groups), the degree of incoherence (a measure of how closely the entire network fits together) was small (omega=0.000017, eight degrees of freedom). The odds ratios were: ARB (five groups) 0.57 (95% CI 0.46-0.72, p<0.0001); ACE inhibitor (eight groups) 0.67 (0.56-0.80, p<0.0001); CCB (nine groups): 0.75 (0.62-0.90, p=0.002); placebo (nine groups) 0.77 (0.63-0.94, p = 0.009); beta blocker (nine groups) 0.90 (0.75-1.09, p=0.30). These estimates changed little in many sensitivity analyses. The association of antihypertensive drugs with incident diabetes is therefore lowest for ARB and ACE inhibitors followed by CCB and placebo, beta blockers and diuretics in rank order.

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Author and article information

Journal

Title: Nature Reviews Cardiology

Abbreviated Title: Nat Rev Cardiol

Publisher: Springer Nature

ISSN (Print): 1759-5002

ISSN (Electronic): 1759-5010

Publication date Created: September 7 2017

Publication date (Print): September 7 2017

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DOI: 10.1038/nrcardio.2017.131

PubMed ID: 28880025

SO-VID: 9f815b5c-2def-421d-a84c-c6f0c6400001

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Expert consensus document: A 'diamond' approach to personalized treatment of angina

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Most cited references 68

Coronary microvascular dysfunction: an update.

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.

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