Diuretics for Hypertension: A Review and Update

Roush, George C.; Sica, Domenic A.

doi:10.1093/ajh/hpw030

Cited by 156 publications

(141 citation statements)

References 60 publications

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“…25 Chlorthalidone only accounted for 3% of prescriptions in patients with resistant hypertension, who may need a more potent diuretic. 26 It is an open question, however, if hydrochlorothiazide has the same cardiovascular benefit as chlorthalidone.…”

Section: Hypertensionmentioning

confidence: 99%

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

et al. 2017

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Abstract-Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications. (Hypertension. 2017;70:94-102.

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Section: Hypertensionmentioning

confidence: 99%

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

et al. 2017

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“…Interestingly, in a small, short-term (12-week) mechanistic study in T2D patients (19), treatment with dapagliflozin (another selective SGLT2 inhibitor) resulted in a smaller reduction in blood pressure than did treatment with a comparator diuretic (25 mg hydrochlorothiazide), but also in a 7% decrease in plasma volume (as directly measured with the use of 125 I-labeled albumin) and some increment in N-terminal pro-BNP levels, neither of which were observed with the treatment with the diuretic agent. Thiazide diuretic agents decrease plasma volume only transiently, whereas in the EMPA-REG OUTCOME trial the observed increase in hematocrit persisted for the entire duration of the trial (20).…”

mentioning

confidence: 92%

CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis

2016

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The striking and unexpected relative risk reductions in cardiovascular (CV) mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) observed in the EMPA-REG OUTCOME trial using an inhibitor of sodium-glucose cotransporter 2 (SGLT2) in patients with type 2 diabetes and high CV risk have raised the possibility that mechanisms other than those observed in the trialdmodest improvement in glycemic control, small decrease in body weight, and persistent reductions in blood pressure and uric acid leveldmay be at play. We hypothesize that under conditions of mild, persistent hyperketonemia, such as those that prevail during treatment with SGLT2 inhibitors, b-hydroxybutyrate is freely taken up by the heart (among other organs) and oxidized in preference to fatty acids. This fuel selection improves the transduction of oxygen consumption into work efficiency at the mitochondrial level. In addition, the hemoconcentration that typically follows SGLT2 inhibition enhances oxygen release to the tissues, thereby establishing a powerful synergy with the metabolic substrate shift. These mechanisms would cooperate with other SGLT2 inhibition-induced changes (chiefly, enhanced diuresis and reduced blood pressure) to achieve the degree of cardioprotection revealed in the EMPA-REG OUTCOME trial. This hypothesis opens up new lines of investigation into the pathogenesis and treatment of diabetic and nondiabetic heart disease.First among cardiovascular (CV) end point trials of glucose-lowering agents (1), the EMPA-REG OUTCOME trialdusing 10 or 25 mg/day sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin against placebo in 7,020 patients with type 2 diabetes (T2D) who were at increased CV riskdreported a 14% reduction in major CV events and marked relative risk reductions in CV mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) over a median time period of 2.6 years (2). Of note, all the pathologic categories of CV death (ischemic, pump failure, arrhythmic, embolic) contributed to the overall reduction in CV death in a patient cohort well treated with the use of renin-angiotensin-aldosterone inhibitors, statins, and acetylsalicylic acid. Furthermore, separation of the cumulative incidence functions between pooled-dose groups and placebo was already evident months after randomization. This unusual time course and the discrepancy between the relative risk reduction of the primary end point (nonfatal myocardial infarction, stroke, and CV mortality) and CV mortality itself suggests that active treatment affected case fatality rates more than event rates. In other words, empagliflozin treatment appeared mostly to rescue patients from impending cardiac decompensation. This interpretation is supported by the recent post hoc analyses of heart failure, documenting a large benefit in first and recurrent heart failure hospitalization across virtually every patient subgroup (3). Despite the fact that the diagnosis of heart failure was based on investigator reporting, th...

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“…RAPL is an antihypertensive drug and HCTZ is a diuretics drug, both of which are used in the treatment of high blood pressure (de Leeuw and Birkenhäger 1987;Roush and Sica 2016). At 0.8% (w/v), dendrimer concentration the RAPL solubility was increased 4.91-fold with amine-terminated dendrimer, whilst the optimal dendrimer for HCTZ solubilisation (3.72-fold) was with carboxy-terminated functional groups.…”

Section: Dendrimersmentioning

confidence: 99%

The use of nanotechnology in cardiovascular disease

2018

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Cardiovascular diseases claim a number of lives globally; many of which are preventable. With the increase in diets that consist of high saturated fat, salt, and sugar, people often living sedentary lifestyles, and a rise in cases of obesity, the incidence of cardiovascular disease is increasing. These contributing factors, coupled with more advanced methods of diagnosis, have delivered statistics that clearly show that there is a rising trend in the prevalence of cardiovascular disease. Treatment for cardiovascular diseases is limited currently to oral medicines or invasive surgery. There is a huge gap in this area of medicine for novel therapeutics for improved patient outcomes. Nanotechnology may provide a solution to more effective treatment of disease, with better prognoses and a reduced side effect profile. This review will explore for potential solutions to the limited pharmacological therapies currently on the market and the future that lies ahead for the place of nanotechnology within cardiovascular medicine.

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Diuretics for Hypertension: A Review and Update

Cited by 156 publications

References 60 publications

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis

The use of nanotechnology in cardiovascular disease

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