Role of Diuretics in the Prevention of Heart Failure

Davis, Barry R.; Piller, Linda B.; Cutler, Jeffrey A.; Furberg, Curt D.; Dunn, Kay; Franklin, Stanley S.; Goff, David C.; Leenen, Frans H. H.; Mohiuddin, Syed M.; Papademetriou, Vasilios; Proschan, Michael A.; Ellsworth, Allan; Golden, John S.; Colon, Pedro; Crow, Richard S.

doi:10.1161/circulationaha.105.544031

Cited by 135 publications

(34 citation statements)

References 47 publications

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“…It concluded that low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality [64]. Furthermore, reduction in arterial BP is very effective in preventing heart failure and diuretics may be superior to other antihypertensive therapies in this respect [65]. Thiazide diuretics, including thiazide-type (chlorothiazide and hydrochlorothiazide) and thiazide-like diuretics (indapamide and chlorthalidone), have been used for the treatment of hypertension for more than 5 decades and are still the most popular diuretics.…”

Section: ) Meta-analyses Of Trials With Cardiovascular Outcome Resulmentioning

confidence: 99%

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

Scheen

2016

Diabetes Research and Clinical Practice

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Please cite this article as: A.J. Scheen, Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: focus on SGLT2 inhibitors and EMPA-REG OUTCOME, Diabetes Research and Clinical Practice (2016), doi: http://dx.doi.org/10.1016/j.diabres. 2016.09.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryEmpagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will : 1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; 2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; 3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and 4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial.

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Section: ) Meta-analyses Of Trials With Cardiovascular Outcome Resulmentioning

confidence: 99%

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

Scheen

2016

Diabetes Research and Clinical Practice

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“…These time points were chosen because they yielded the best-fitting models, according to log-likelihood scores. 26,27 Covariate adjustment in Cox models included age (introduced as an exponential term, which yielded a more robust association with mortality), gender, treatment variables and BP-monitoring variables. BMI was not included, as it did not predict mortality in this database.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in structure would affect BP reactivity, and hence its variability, during the varying stresses of the awake and asleep periods. Indeed, in the largest hypertension study to date, 26 the effect of antihypertensive medications on congestive heart failure outcome was also blunted with time. As the relationship of BP to heart failure is indisputable, similarly the blunting over time of the BPVR prediction of all-cause mortality should not be an argument to nullify its importance.…”

Section: Discussionmentioning

confidence: 99%

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The association of a simple blood pressure-independent parameter derived from ambulatory blood pressure variability with short-term mortality

et al. 2009

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We explored the predictive ability of the blood pressure variability ratio (BPVR), defined as the ratio of 24-h ambulatory systolic blood pressure variability to diastolic variability, and evaluated its predictable relation with blood pressure and the Ambulatory Arterial Stiffness Index (AASI). A total of 3433 consecutive patients were followed up to 16 years for all-cause mortality. Blood pressure variability was expressed by the standard deviation. BPVR, which is the systolic-on-diastolic slope estimated by a known type of symmetric regression ('reduced major axis'), was compared with other expressions of this slope and with AASI using other regression procedures. Time-dependent Cox proportional hazard models, adjusted for demographics, 24-h mean blood pressure, 24-h pulse pressure and dipping were used to assess the association of BPVR and slope-related parameters with all-cause mortality. We found that Pearson's correlation between BPVR and the symmetric slope was 0.957, and between 1-1/BPVR (an AASI-equivalent expression) and the symmetric version of AASI was 0.973. BPVR was entirely independent of mean arterial pressure (r¼0.013). Systolic and diastolic ambulatory blood pressure variability was not significantly associated with mortality. Over 16 years, BPVR predicted all-cause mortality [hazard ratio¼1.21 (95% CI 1.05-1.40) per 1 s.d. increase]. In time-dependent models, increased BPVR was strongly associated with an 18-month mortality, weakly related to 7 years mortality, showing no effect thereafter. Thus, the ratio between 24-h systolic and diastolic blood pressure variability, readily available from ambulatory monitoring reports, is an easy-to-calculate systolic-on-diastolic slope. It is a blood pressureindependent measure believed to express an arterial property, with prognostic power similar to that of AASI.

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“…8 Clinical trial data have also revealed similar associations between diabetes and HF. In the ALLHAT, Davis et al 9 found that patients with diabetes had a nearly 2-fold risk for HF hospitalization or death after adjustment for other risk factors (RR, 1.95). The association with diabetes was independent from and equivalent in degree to that of coronary artery disease and greater than that for electrocardiographic left ventricular hypertrophy and renal dysfunction.…”

Section: Incidencementioning

confidence: 99%

Review article: Diabetes mellitus and heart failure — an overview of epidemiology and management

Baliga

Sapsford

2009

Diabetes and Vascular Disease Research

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HF has been a major health concern for a number of years, and is a leading cause for hospitalisation in patients over 65 years old.1 DM is a chronic progressive disease, and is a well recognised risk factor for HF. [2][3][4][5] The Framingham Heart Study first demonstrated over 20 years ago an increased risk of congestive HF in patients with diabetes. 6Over the years, they have been mostly treated as separate entities, but often a significant overlap exists.In this article, we discuss the epidemiological characteristics, the associated mortality and morbidity and the management of these two inter-related conditions. IncidenceDM is an independent risk factor for development of HF.4 Population studies such as the Cardiovascular Health Study have clearly shown DM as an independent risk factor for HF, with a HR of 1.74 (1.38-2.19). 4 The Framingham study showed the risk of HF was 2-fold higher in men and 5-fold higher in women with diabetes. 6 The association was even stronger in younger patients (ages ≤ 65 years), being 4-fold higher in male patients and 8-fold higher in female patients with diabetes than in subjects without diabetes. A large survey of patients in a Kaiser Permanente database showed that in subjects with diabetes HF approximately doubled from 33 cases per 1,000 for subjects aged 45-54 years to 68 cases per 1,000 for those aged 55-64 years; it then doubled again to 135 cases per 1,000 for subjects aged 65-74 years.7 In a study of elderly nursing home residents initially free of HF, 39% of those with diabetes vs. 23% of those without diabetes had developed HF after 43 months of follow-up; RR, 1.3. 8Clinical trial data have also revealed similar associations between diabetes and HF. In the ALLHAT, Davis et al. 9 found that patients with diabetes had a nearly 2-fold risk for HF hospitalization or death after adjustment for other risk factors (RR, 1.95). The association with diabetes was independent from and equivalent in degree to that of coronary artery disease and greater than that for electrocardiographic left ventricular hypertrophy and renal dysfunction. The UKPDS demonstrated that the incidence of HF in patients with diabetes correlated with HbA Heart failure and Diabetes mellitus are chronic complex medical conditions that are closely related and commonly coexist. Treatment options have varied over the years, but newer treatment modalities have developed which have improved prognosis and longevity of patients with these conditions. Unfortunately, despite these advances, the evidence base remains insufficient, and larger randomised control trials need to be conducted. Here we discuss the available evidence and treatment and management of these inter-related conditions.

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Role of Diuretics in the Prevention of Heart Failure

Cited by 135 publications

References 47 publications

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

The association of a simple blood pressure-independent parameter derived from ambulatory blood pressure variability with short-term mortality

Review article: Diabetes mellitus and heart failure — an overview of epidemiology and management

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