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Cardiovascular conditions such as hypertension, arrhythmias, and heart failure are common in patients undergoing anesthesia for surgical or other procedures. Numerous guidelines from various specialty societies offer variable recommendations for the perioperative management of these medications. The Society for Perioperative Assessment and Quality Improvement identified a need to provide multidisciplinary evidence-based recommendations for preoperative medication management. The society convened a group of 13 members with expertise in perioperative medicine and training in anesthesiology or internal medicine. The aim of this consensus effort is to provide perioperative clinicians with guidance on the management of cardiovascular medications commonly encountered during the preoperative evaluation. We used a modified Delphi process to establish consensus. Twenty-one classes of medications were identified: α-adrenergic receptor antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, β-adrenoceptor blockers, calcium-channel blockers, centrally acting sympatholytic medications, direct-acting vasodilators, loop diuretics, thiazide diuretics, potassium-sparing diuretics, endothelin receptor antagonists, cardiac glycosides, nitrodilators, phosphodiesterase-5 inhibitors, class III antiarrhythmic agents, potassium-channel openers, renin inhibitors, class I antiarrhythmic agents, sodium-channel blockers, and sodium glucose cotransportor-2 inhibitors. We provide recommendations for the management of these medications preoperatively.

The thiazide-sensitive Na+-Cl− cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule, and the inhibition of its function with thiazides is widely used for the treatment of arterial hypertension. In mammals and teleosts, NCC is present as one ortholog that is mainly expressed in the kidney. One exception, however, is the eel, which has two genes encoding NCC. The eNCCα is located in the kidney and eNCCβ, which is present in the apical membrane of the rectum. Interestingly, the European eNCCβ functions as a Na+-Cl− cotransporter that is nevertheless resistant to thiazides and is not activated by low-chloride hypotonic stress. However, in the Japanese eel rectal sac, a thiazide-sensitive NaCl transport mechanism has been described. The protein sequences between eNCCβ and jNCCβ are 98% identical. Here, by site-directed mutagenesis, we transformed eNCCβ into jNCCβ. Our data showed that jNCCβ, similar to eNCCβ, is resistant to thiazides. In addition, both NCCβ proteins have high transport capacity with respect to their renal NCC orthologs and, in contrast to known NCCs, exhibit electrogenic properties that are reduced when residue I172 is substituted by A, G, or M. This is considered a key residue for the chloride ion-binding sites of NKCC and KCC. We conclude that NCCβ proteins are not sensitive to thiazides and have electrogenic properties dependent on Cl−, and site I172 is important for the function of NCCβ.

Individuals with chronic hypoparathyroidism may experience suboptimal medical care with high frequency of unplanned hospitalisation and iatrogenic harm. In 2015 the European Society for Endocrinology published consensus guidelines on the management of chronic hypoparathyroidism. We set out to audit compliance with these guidelines.Using these recommendations as audit standards we worked with the Society for Endocrinology and Parathyroid UK to conduct a national audit of management of chronic hypoparathyroidism in the United Kingdom. Endocrine leads in 117 endocrine departments were invited to participate in the survey by completing a data collection tool on up to 5 sequential cases of chronic hypoparathyroidism seen in their outpatient clinics in the preceding 12 months. Data were collected on 4 treatment standards and 9 monitoring standards. Data on hospitalisations and Quality of Life monitoring were also collected.Responses were received from 22 departments giving a response rate of 19%, concerning 80 individual cases. The mean age of subjects was 48.4 years. The main findings were that the commonest cause of hypoparathyroidism was post surgical (66.3%). Treatments taken by the group included activated vitamin D analogues (96.3%), oral calcium salts (66.3%), vitamin D supplements (17.5%), thiazide diuretics (5%) and rhPTHsub1-34/sub(1.3%). Compliance with the audit standards varied between 98.8% and 60% for the treatment standards and between 91.3% and 20% for the monitoring standards. Some of the areas of weakness revealed include low rates of 24 h urinary calcium excretion monitoring, serum magnesium monitoring and low rates of renal imaging where indicated. In addition and importantly, 16.3% of subjects had experienced at least one hospital admission in the preceding 12 months.We conclude that further improvements in the UK national standard of management of chronic hypoparathyroidism should be made and that this will benefit both quality of life, morbidity and potentially mortality in this group of patients.

Existing guidelines offer little direction about the use of thiazide and loop diuretics in patients with chronic kidney disease (CKD). This review summarizes recent studies impacting indications and safety considerations for these agents in patients with CKD.Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower glomerular filtration rates (GFR). Existing studies show no clear impact of thiazide or loop diuretic use on kidney or cardiovascular outcomes in patients with CKD. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have diuretic effects, but concomitant use of a diuretic does not diminish the preventive benefits of these agents against acute kidney injury (AKI). Despite theoretical concerns, thiazide diuretics likely do not worsen circulating vasopressin levels or cyst progression in polycystic kidney disease and may be useful for alleviating polyuria from tolvaptan. Diuretics cause multiple adverse effects, including electrolyte abnormalities, hemodynamic-mediated decrease in estimated GFR, and AKI.Recent evidence supports expanded indications for diuretics in patients with kidney disease, including chlorthalidone for hypertension in advanced CKD. Monitoring electrolytes and estimated GFR is critical to ensure patient safety when prescribing these agents for patients with CKD.

Background: The primary objective of this analysis is to assess if greater exposure to any major antihypertensive drug class was associated with reduced primary composite outcome events in SPRINT (Systolic Blood Pressure Intervention Trial). Methods: This is a secondary analysis of the SPRINT trial evaluating whether longitudinal, time varying exposure to any major antihypertensive drug class had any impact on primary outcome events, after adjusting for effects of randomization arm, time varying achieved systolic blood pressure, other drug class exposure, and baseline characteristics. Results: Nine thousand two hundred fifty-two participants were included. After adjustments, exposure of one year or greater to thiazide-type diuretics or renin-angiotensin system blockers was associated with significantly fewer primary events than exposure of less than one year (hazard ratio, 0.78 [95% CI, 0.64–0.94]). There was no significant difference with longer versus shorter exposure to calcium channel blockers. Greater exposure to beta-blockers was associated with an increase in primary events compared with exposure of Conclusions: The SPRINT trial demonstrated a lower target blood pressure led to reductions in adverse cardiovascular events. This analysis suggests greater exposure to thiazide-type diuretics and renin-angiotensin system blockers also contributed to reduced adverse cardiovascular events. Greater exposure to beta-blockers was associated with increased cardiovascular events.

Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. This traditional classification and the nomenclature of diuretics have not changed over the last decades, which means that it was not adapted to current pharmacological research. Modern approaches in the field of pharmacological nomenclature suggest the introduction of mechanism-based drug class designations, which is not yet reflected in the group of diuretics. Moreover, included drug classes have lost their relevance as diuretic agents. Carbonic anhydrase inhibitors, for example, are mainly used in the treatment of glaucoma. Newer agents such as vasopressin-2 receptor antagonists or SGLT2 inhibitors possess diuretic properties but are not included in the pharmacological group. This review discusses the currentness of the pharmacological classification of diuretics. We elaborate changes in the field of nomenclature, the contemporary medical use of classical diuretics, and new diuretic agents.

Background The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. Methods A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database (ClinicalTrials.gov), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. Discussion To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. Trial registration This systematic review and network meta-analysis was prospectively registered at the PROSPERO database (CRD42018118492).

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for β-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P =0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P =0.204), although CCB monotherapy increased (29.5% versus 21.0%, P =0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P =0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

The association between the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors and the occurrence of drug-induced kidney injury has not been evaluated. This study assessed whether the use of SGLT-2 inhibitors decreases the risk of drug-induced acute kidney injury (AKI) using the US Food and Drug Administration's Adverse Event Reporting System (FAERS) and the Medical Data Vision (MDV) database. The occurrence of AKI in SGLT-2 inhibitor users and dipeptidyl peptidase-4 (DPP-4) inhibitor users was compared using both databases. In FAERS analysis, disproportionality for AKI was observed between DPP-4 inhibitor users and SGLT-2 inhibitor users administered non-steroidal anti-inflammatory drugs (reporting odds ratio [ROR] 0.65, 95% confidence interval [CI] 0.48-0.88, P < 0.01) and thiazide diuretics (ROR 0.78, 95% CI 0.67-0.90; P < 0.01). In MDV analysis, SGLT-2 inhibitor users administered non-steroidal anti-inflammatory drugs (odds ratio [OR] 0.46, 95% CI 0.41-0.53, P < 0.01), anti-herpes simplex virus drugs (OR 0.20, 95% CI 0.07-0.53, P < 0.01), thiazide diuretics (OR 0.50, 95% CI 0.36-0.71, P < 0.01), and loop diuretics (OR 0.71, 95% CI 0.62-0.83, P < 0.01) had a lower incidence of AKI compared with DPP-4 inhibitor users receiving the same drugs. No differences were observed in the risk of AKI between SGLT-2 and DPP-4 inhibitor users administered vancomycin and cisplatin in both databases. The use of SGLT-2 inhibitors might reduce the risk of drug-induced AKI caused by some drugs. This article is protected by copyright. All rights reserved.

Hypoparathyroidism remains the single endocrine deficiency disease that is not habitually treated with the missing hormone. In this article, we aim to provide a review of the conventional approach and the novel therapies as well as an overview of the perspectives on the treatment of this rare condition. We conducted a literature review on the conventional therapy using vitamin D analogs and calcium salts, indications for thiazide diuretics and phosphorus binders, PTH analogs history and usage, and the drugs that are currently being tested in clinical trials. Conventional treatment involves calcium salts and vitamin D analogs. Thiazide diuretics can be used to reduce hypercalciuria in some cases. A low-phosphate diet is recommended, and phosphate binders are rarely needed. During pregnancy, a careful approach is necessary. The use of PTH analogs is a new approach despite the limitation of high cost. Studies have included modified PTH molecules, calcilytics, microencapsulation of human parathyroid cells, and allotransplantation.

Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P0.001).In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Background and objectives In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. Design, setting, participants, & measurements A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30–89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). Results There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was −3.8 g (95% confidence interval, −8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (−0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). Conclusions Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.

Background: Thiazide diuretics are a mainstay in the management of hypertension and often associated with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia and hypokalemia in thiazide users, substance-specific differences, and the association of thiazides with syncope and falls. Methods: In this cross-sectional analysis all patients admitted to an interdisciplinary emergency department in Switzerland between January 1, 2017, and December 31, 2018, with measurements of serum sodium and potassium were included. Data regarding serum electrolytes and creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney injury. Chart reviews were performed to screen for syncope or falls. Results: A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent effect was found for electrolyte disorders, and there was a variance in risk between the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk. Patients taking thiazide diuretics had significantly more episodes of syncope and falls. Conclusions: Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears to be dose-dependent and highly variable depending on the substance. Syncope and falls seem to be causally related to thiazide use. Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned.

Hypertension is often difficult to control in patients with CKD as manifested by suboptimal control rates in this population. Use of thiazides in CKD patients has been limited as these agents are thought to be ineffective in reducing blood pressure in people with advanced CKD. This review summarizes recent studies impacting indications and safety of use of thiazide in patients with CKD and discusses the mechanism of how thiazides reduce blood pressure.Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower levels of GFR. Recent clinical trial data indicate that thiazides are effective in patients with advanced kidney disease for blood pressure lowering. However, monitoring of electrolytes and kidney function is important to ensure patient safety when prescribing these agents in patients with CKD.

Background Pharmacy fill data are a practical tool for assessing medication nonadherence. However, previous studies have not compared the accuracy of pharmacy fill data to measurement of plasma drug levels, or chemical adherence testing (CAT). Methods and Results We performed a cross‐sectional study in patients with uncontrolled hypertension in outpatient clinics in a safety net health system. Plasma samples were obtained for measurement of common cardiovascular drugs, including calcium channel blockers, thiazide diuretics, beta blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, and statins, using liquid chromatography mass spectrometry. Proportion of days covered (PDC), a method for tracking pharmacy fill data, was calculated via linkages with Surescripts, and its diagnostic test characteristics were compared with CAT. Among 77 patients with uncontrolled hypertension, 13 (17%) were nonadherent to at least 1 antihypertensive drug and 23 (37%) were nonadherent to statins by CAT. PDC was significantly lower in the nonadherent versus the adherent group by CAT only among patients prescribed an angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker or statin (all P Conclusions PDC is useful in detecting nonadherence to angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and statins but has limited usefulness in detecting nonadherence to calcium channel blockers, beta blockers, or thiazide diuretics and has a low positive predictive value for all drug classes.

Background The co-administration of loop diuretics with thiazide diuretics is a therapeutic strategy in patients with hypertension and volume overload. The aim of this study was to assess the efficacy and safety of treatment with bumetanide plus chlorthalidone in patients with chronic kidney disease (CKD) stage 4–5 KDIGO. Methods A double-blind randomized study was conducted. Patients were randomized into two groups: bumetanide plus chlorthalidone group (intervention) and the bumetanide plus placebo group (control) to evaluate differences in TBW, ECW and ECW/TBW between baseline and 30 Days of follow-up. Volume overload was defined as ‘bioelectrical impedance analysis as fluid volume above the 90th percentile of a presumed healthy reference population. The study’s registration number was NCT03923933. Results Thirty-two patients with a mean age of 57.2 ± 9.34 years and a median estimated glomerular filtration rate (eGFR) of 16.7 ml/min/1.73 m2 (2.2–29) were included. There was decreased volume overload in the liters of total body water (TBW) on Day 7 (intervention: -2.5 vs. control: -0.59, p = 0.003) and Day 30 (intervention: -5.3 vs. control: -0.07, p = 0.016); and in liters of extracellular water (ECW) on Day 7 (intervention: -1.58 vs. control: -0.43, p p p = 0.073) and Day 30 (intervention: -26.1 vs. control: -10, p = 0.028) and in diastolic blood pressure on Day 7 (intervention: -8.5 vs. control: -2.25, p = 0.059) and Day 30 (intervention: -13.5 vs. control: -3.4, p = 0.018). Conclusion In CKD stage 4–5 KDIGO without renal replacement therapy, bumetanide in combination with chlorthalidone is more effective in treating volume overload and hypertension than bumetanide with placebo.

Background In typical cases of Bartter syndrome (BS), assessing response to diuretics (furosemide and thiazide), hereinafter referred to as diuretic loading test, may be used to diagnose the type by detecting which part of the kidney tubule is not functioning correctly. However, the diuretic loading test may not always agree with the results of genetic analyses. Case presentation A 5-year-old boy was admitted due to lower extremity weakness and abnormal gait. He had a recurrent episode of muscle weakness and laboratory results showed severe hypokalemia. The direct genomic sequencing of the case revealed a new mutation in the SLC12A1 gene, which is associated with type I Bartter syndrome. Because there was the difference between the phenotype and genotype, we conducted a diuretic loading test to confirm the diagnosis. However, the results showed a clear increase in urine excretion of Na and Cl. These results were not consistent with typical type I BS, but consistent with the patient’s phenotype. Conclusion The diuretic loading test has limited utility for diagnosis especially in atypical cases. On the other hand, this test, which allows assessment of channel function, is useful for better understanding of the genotype-phenotype correlation.

Purpose Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. Patients and Methods This study was a non‐interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End‐Results (SEER)‐Medicare database. The association between AH drug utilization on AJCC stage I–III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. Results The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer‐specific mortality (HR: 0.79, 95% CI: 0.75–0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80–0.87), beta‐blockers (HR: 0.87, 95% CI: 0.84–0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80–0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer‐specific mortality (HR: 0.94, 95% CI: 0.90–0.98). Conclusion Further research needs to be performed, but AH medications may present a promising, low‐cost pathway to supporting CRC treatment for stage I–III cancers., The use of antihypertensive agents following colorectal cancer diagnosis is associated with lower mortality (both all‐cause and cancer‐specific) in elderly Medicare patients. Among the studied classes of antihypertensives, ACE inhibitors and beta‐blockers seem to be associated with protective associations.

ObjectivesTo describe the prescribing trends of antihypertensive drugs in primary care patients and assess the trajectory of antihypertensive drug prescriptions, from first-line to third-line, in patients with hypertension according to changes to the United Kingdom (UK) hypertension management guidelines.DesignPopulation-based cohort study.Setting and participantsWe used the UK Clinical Practice Research Datalink, an electronic primary care database representative of the UK population. Between 1988 and 2018, we identified all adult patients with at least one prescription for a thiazide diuretic, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta-blocker or calcium channel blocker (CCB).Primary and secondary outcome measuresWe estimated the period prevalence of patients with antihypertensive drug prescriptions for each calendar year over a 31-year period. Treatment trajectory was assessed by identifying patients with hypertension newly initiating an antihypertensive drug, and treatment changes were defined by a switch or add-on of a new class. This cohort was stratified before and after 2007, the year following important changes to UK hypertension management guidelines.ResultsThe cohort included 2 709 241 patients. The prevalence of primary care patients with antihypertensive drug prescriptions increased from 7.8% (1988) to 21.9% (2018) and was observed for all major classes except thiazide diuretics. Patients with hypertension initiated thiazide diuretics (36.8%) and beta-blockers (23.6%) as first-line drugs before 2007, and ACE inhibitors (39.9%) and CCBs (31.8%) after 2007. After 2007, 17.3% were not prescribed guideline-recommended first-line agents. Overall, patients were prescribed a median of 2 classes (IQR 1–2) after first-line treatment.ConclusionNearly one-quarter of primary care patients were prescribed antihypertensive drugs by the end of the study period. Most patients with hypertension initiated guideline-recommended first-line agents. Not all patients, particularly females, were prescribed recommended agents however, potentially leading to suboptimal cardiovascular outcomes. Future research should aim to better understand the implication of this finding.

Purpose Thiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden. Methods Population-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides. Results Individuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28–89). The associations gradually declined reaching an aOR of 2.9 (2.7–3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia. Conclusions Thiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.

Objective To assess whether angiotensin II–stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II–inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the “angiotensin hypothesis.” Methods We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6–8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70–78 (mean 74.5 ± 2.5) years. Results After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II–stimulating, 8.2% (59/721) in angiotensin II–inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II–stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34–0.89) without excess mortality (HR, 0.86; 95% CI, 0.64–1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53–1.20) without excess mortality (HR, 0.97; 95% CI, 0.76–1.24), compared to angiotensin II–inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease. Conclusions Users of angiotensin II–stimulating antihypertensives had lower dementia rates compared to angiotensin II–inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.