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1.
Heart failure drug treatment.
Rossignol, P, Hernandez, AF, Solomon, SD, Zannad, F
Lancet (London, England). 2019;(10175):1034-1044
Abstract
Heart failure is the most common cardiovascular reason for hospital admission for people older than 60 years of age. Few areas in medicine have progressed as remarkably as heart failure treatment over the past three decades. However, progress has been consistent only for chronic heart failure with reduced ejection fraction. In acutely decompensated heart failure and heart failure with preserved ejection fraction, none of the treatments tested to date have been definitively proven to improve survival. Delaying or preventing heart failure has become increasingly important in patients who are prone to heart failure. The prevention of worsening chronic heart failure and hospitalisations for acute decompensation is also of great importance. The objective of this Series paper is to provide a concise and practical summary of the available drug treatments for heart failure. We support the implementation of the international guidelines. We offer views on the basis of our personal experience in research areas that have insufficient evidence. The best possible evidence-based drug treatment (including inhibitors of the renin-angiotensin-aldosterone system and β blockers) is useful only when optimally implemented. However, implementation might be challenging. We believe that disease management programmes can be helpful in providing a multidisciplinary, holistic approach to the delivery of optimal medical care.
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2.
Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects.
Moon, SJ, Jeon, JY, Yu, KS, Kim, MG
Clinical therapeutics. 2019;(11):2273-2282
Abstract
PURPOSE Hypertension is a major risk factor for cardiovascular diseases, necessitating hypertension control. Antihypertensive drugs are more potent when administered in combinations of 2 or 3 different classes of drugs. One such therapy includes a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. The objective of this study was to evaluate the pharmacokinetic interaction among telmisartan, amlodipine, and hydrochlorothiazide. METHODS A randomized, open-label, 3-period, 6-sequence, 3-treatment, single-dose crossover study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 6 sequences and one of the following treatments was administered in each period: treatment A, co-administration of one tablet of telmisartan 80 mg and one tablet of amlodipine 10 mg; treatment B, one tablet of hydrochlorothiazide 25 mg alone; and treatment C, co-administration of all 3 investigational products. Serial blood samples were collected up to 144 hours postdose. Plasma drug concentrations were measured by using LC/MS-MS. Pharmacokinetic parameters, including Cmax and AUC0-last, were determined by using noncompartmental analysis. The geometric least squares mean ratios and associated 90% CIs of log-transformed Cmax and AUC0-last for separate administration or co-administration were calculated to evaluate pharmacokinetic interactions. FINDINGS Twenty-seven subjects completed the study. The geometric least squares mean ratios and 90% CIs of Cmax and AUC0-last were 1.02 (0.85-1.21) and 1.04 (0.97-1.13) for telmisartan; 1.00 (0.95-1.04) and 0.95 (0.91-0.99) for amlodipine; and 0.88 (0.82-0.96) and 0.86 (0.82-0.90) for hydrochlorothiazide, respectively. No serious adverse events were recorded, and all reported adverse events were of mild intensity. IMPLICATIONS The pharmacokinetic parameters of telmisartan, amlodipine, and hydrochlorothiazide when administered separately or co-administered were compared, and all the parameters met the criteria for pharmacokinetic equivalence. Combination therapy of these 3 drugs had no significant impact on the pharmacokinetic parameters of each drug. (ClinicalTrials.gov Identifier: NCT03889145).
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3.
Can We Predict the Outcome of Oral Dissolution Therapy for Radiolucent Renal Calculi? A Prospective Study.
Elsawy, AA, Elshal, AM, El-Nahas, AR, Elbaset, MA, Farag, H, Shokeir, AA
The Journal of urology. 2019;(2):350-357
Abstract
PURPOSE We prospectively assessed the efficacy and the predictors of the success of oral dissolution therapy by alkalization for lucent renal calculi. MATERIALS AND METHODS Patients with radiolucent renal stones were counseled to undergo oral dissolution therapy, which entails oral potassium citrate 20 mEq 3 times daily, 3 L daily fluid intake and a dietary regimen. The study primary end point was the achievement of a 6-month stone-free rate with oral dissolution therapy. The other end point was a change in stone surface area as measured by noncontrast computerized tomography at 3 and 6 months. RESULTS Between February 2015 and January 2016 only 182 of the 212 eligible patients who agreed to participate were compliant with oral dissolution therapy and included in the final analysis. Mean stone surface area at enrollment was 1.3 cm (range 0.16 to 11.84). At 3 months 97 (53.2%), 65 (35.7%) and 20 (11.1%) patients were oral dissolution therapy responders (stone-free), partial responders and nonresponders, respectively. Oral dissolution therapy achieved a 6-month stone-free rate of 83%, including 97 and 54 patients after 3 and 6 months of oral dissolution therapy, respectively. On regression analysis the initial 3-month response to oral dissolution therapy (p = 0.001), lower stone density (p = 0.03) and higher urine pH 12 weeks after treatment (p = 0.01) independently predicted the oral dissolution therapy response at 6 months. CONCLUSIONS Regardless of stone size, oral dissolution therapy was an effective treatment approach for lucent renal stones. The initial response to oral dissolution therapy after 3 months was the key factor in determining the potential oral dissolution therapy response after 6 months. In addition, treatment compliance in achieving the targeted urine pH and low stone density has an independent role in the oral dissolution therapy response.
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4.
The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology.
Mullens, W, Damman, K, Harjola, VP, Mebazaa, A, Brunner-La Rocca, HP, Martens, P, Testani, JM, Tang, WHW, Orso, F, Rossignol, P, et al
European journal of heart failure. 2019;(2):137-155
Abstract
The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.
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5.
Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia.
Bianchi, S, Regolisti, G
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii51-iii61
Abstract
Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.
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6.
Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics.
Upadhya, B, Lovato, LC, Rocco, M, Lewis, CE, Oparil, S, Cushman, WC, Kostis, JB, Rodriguez, CJ, Cho, ME, Cloud, LW, et al
JACC. Heart failure. 2019;(12):1032-1041
Abstract
OBJECTIVES This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study. BACKGROUND SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications. METHODS Detailed use of medication data prospectively collected throughout the trial were examined. RESULTS ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83). CONCLUSIONS No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).
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7.
Hyponatremia-Inducing Drugs.
Liamis, G, Megapanou, E, Elisaf, M, Milionis, H
Frontiers of hormone research. 2019;:167-177
Abstract
In clinical practice, several medications such as diuretics, psychotropic drugs, and anticonvulsants have been reported to be a frequent cause of hyponatremia. Drugs may cause hyponatremia either by affecting the homeostasis of sodium and water (e.g., diuretics) or by altering the water homeostasis as a consequence of the syndrome of inappropriate secretion of antidiuretic hormone. On the contrary, drugs commonly prescribed in everyday clinical practice, including proton pump inhibitors, antibiotics, angiotensin-converting enzyme inhibitors, hypoglycemic agents and, amiodarone, have been infrequently 'incriminated' as causes of hyponatremia. Therefore, in the diagnostic approach of patients with low serum [Na+] levels, meticulous history taking and recording of pharmacotherapy is warranted to identify potentially culprit medications. Taking into account the adverse outcomes associated with even mild hyponatremia (i.e., impaired cognition, falls and fractures, mortality), recognition of drug-induced hyponatremia is of vital importance, while responsible agents should be discontinued and "re-challenge" should be avoided by informing the patient and involved caregivers.
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8.
Ascites and Hepatorenal Syndrome.
Adebayo, D, Neong, SF, Wong, F
Clinics in liver disease. 2019;(4):659-682
Abstract
Ascites occurs in up to 70% of patients during the natural history of cirrhosis. Management of uncomplicated ascites includes sodium restriction and diuretic therapy, whereas that for refractory ascites (RA) is regular large-volume paracentesis with transjugular intrahepatic portosystemic shunt being offered in appropriate patients. Renal impairment occurs in up to 50% of patients with RA with type 1 hepatorenal syndrome (HRS) being most severe. Liver transplant remains the definitive treatment of eligible candidates with HRS, whereas combined liver and kidney transplant should be considered in patients requiring dialysis for more than 4 to 6 weeks or those with underlying chronic kidney disease.
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9.
Prevention of Contrast-induced Nephropathy in Patients with Chronic Kidney Disease Undergoing Elective Coronary Angioplasty or Angiography with Sodium Potassium Citrate Solution, a Double Blind Randomized Clinical Trial.
Ghorbani, A, Yazdankhah, S, Adel, MH, Tabesh, H, Sattari, AR, Sattari, SA, Heybar, H, Madjidi, S
Iranian journal of kidney diseases. 2019;(3):182-190
Abstract
INTRODUCTION Contrast-induced nephropathy (CIN) is a frequent complication of contrast exposure. A recent study suggested that Na/K citrate might have a preventive role. We investigated the efficacy of Na/K citrate to prevent CIN in patients with renal dysfunction undergoing coronary intervention. METHODS The randomized, double-blind, placebo-controlled trial included 201 patients with estimated creatinine clearance < 90 mL/ min, randomized to receive oral Na/K citrate plus saline infusion (treatment group, 104 patients) or oral water plus saline infusion (placebo group, 97 patients). CIN was defined as an absolute increase of serum creatinine ≥ 0.5 mg/dL or a relative increase ≥ 25% or a relative decrease of estimated GFR ≥ 25% within 5 days. RESULTS CIN occurred in 22 patients (12.29%); 10 (11%) in treatment group and 12 (13.6%) in placebo group (P > .05). Post-exposure Cr values were not significantly different between the two groups (1.18 ± 0.28 mg/dL in the placebo vs. 1.15 ± 0.29 mg/dL in the treatment group, P > .05). CIN-negative patients in the treatment group showed a significantly higher increase in urine pH than that of CIN-positive patients (1.642 ± 0.577 vs. 1.20 ± 0.422, P < .05). CONCLUSION Na/K citrate solution is not effective for prophylaxis of CIN in patients with renal dysfunction. However, a probable preventive effect might exist in a subgroup of patients with at least 1.6 units increase in urine pH values following Na/K citrate administration.
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10.
Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope.
Bo, M, Ceccofiglio, A, Mussi, C, Bellelli, G, Nicosia, F, Riccio, D, Martone, AM, Langellotto, A, Tonon, E, Tava, G, et al
European journal of internal medicine. 2019;:34-39
Abstract
BACKGROUND Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study. METHODS Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12‑lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed. RESULTS Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34-3.26) and diuretics use (OR 1.85; 95% CI 1.18-2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with one-year mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01-3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase. inhibitors and antipsychotics, but not with prolonged QTc. CONCLUSIONS We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF.