Guideline-directed medical therapy in heart failure patients with reduced ejection fraction in Oman: utilization, reasons behind non-prescribing, and dose optimization.

Background Objective: To determine the reasons behind guideline-directed medical therapy (GDMT) non-prescribing, drug utilization before and after excluding those intolerable to GDMT, as well as dose optimization in heart failure (HF) patients with reduced ejection fraction (<40%) (HFrEF) in Oman. Methods: The study included HF patients seen at the medical outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January 2016 and December 2019 and followed up until the end of June 2021. The use of renin-angiotensin-system (RAS) blockers (angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs)), beta blockers and mineralocorticoid receptor antagonists (MRAs) were evaluated as per the European, American, and Canadian HF guidelines. Analyses were performed using univariate statistics. Results: A total of 171 HFrEF patients were enrolled for this study, the overall mean age of the cohort was 63 ± 15 years old and 59% were male. Over 65% of the patients had chronic kidney disease. Almost 55% of the patients were intolerable to GDMT. The proportion of patients on beta blockers, RAS blockers/ hydralazine-isosorbide dinitrate combination, and MRAs, before and after excluding those intolerable to GDMT, were 89%, 97%, and 77%, and, 94%, 47% and 85%, respectively, while the proportion of patients on the GDMT combination concomitantly was 41% and 83%, respectively. A total of 61%, 44% and 100% of the patients were prescribed ≥50% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively, while 19%, 8.2% and 94% of the patients attained 100% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively. Conclusions: Reasons behind GDMT non-prescribing were frequent and not clearly obvious in patients' medical notes. The majority of the patients were prescribed GDMT. However, dose optimization, specifically for beta blockers and RAS blockers/ HYD-ISDN combination, was still suboptimal. The findings should be interpreted in the context of low study power and that future studies, with larger sample sizes, are warranted to minimize this limitation.

A snapshot on the usage pattern of gabapentinoids in Oman.

Background: Since their introduction as adjunct anticonvulsants, the use of gabapentinoids (gabapentin and pregabalin) has increased substantially worldwide to include a wide range of clinical conditions. Various reports have demonstrated that they possess addiction liability and can produce effects similar to traditional recreational drugs, such as significant euphoric effects, enhanced sociability, and relaxation. However, there is limited information on the use of these agents in the Middle East. Objectives: Here, we describe the usage pattern of gabapentinoids at Sultan Qaboos University Hospital, a tertiary care medical institution in Oman. Methods: Adult patients (≥18 years) who were prescribed gabapentinoids for six months (March-August 2019) were included in this retrospective cross-sectional study. Indications and dosing regimens were reviewed according to the Food and Drug Administration labeling. Controlled and restricted drugs were reviewed using Oman National Formulary. Institutional ethical approval was obtained before conducting the study. Results: We analyzed 291 prescriptions. The mean (standard deviation, SD) age was 60.5 years (SD = 13.0) with the age group of ≥60 years being the most common (190, 65.3%). Most of patients were females (178, 61.2%). The majority of prescriptions were for outpatients (85.8%). Drugs were prescribed as refill and follow-up in 116 (40.0%) and 97 (33.4%) of prescriptions, respectively. Diabetic peripheral neuropathy (50, 79.4%) was the most labeled indication for both. Off-label use was 128 (51.8%) and 31 (70.5%) for pregabalin and gabapentin, respectively, with lower back pain as being the most common indication for both drugs. A total of 54 (19.0%) patients were using at least one of the psychotropic drugs. Conclusions: Our findings indicate that gabapentinoids are frequently prescribed for off-label use. Awareness programs and the establishment of policy for the use of these drugs are required to ensure their rational use and prevent misuse and/or abuse.

Evaluation of guideline-based cardiovascular medications and their respective doses in heart failure patients in Oman.

Background Significant gaps exist between guidelines and practice in the management of heart failure, not only in Oman but the Arabian Gulf region in general. Currently, only limited research exists on the use of these guideline-based cardiovascular medications and their corresponding target doses in the region. Objective To evaluate the use of guideline-based cardiovascular medications and their corresponding target doses in heart failure patients with reduced (< 40%) and mid-range (40-49%) ejection fraction in Oman. Setting Cardiology clinics at Sultan Qaboos University Hospital, Muscat, Oman. Methods The study included heart failure patients seen at the clinics between January 2016 and December 2019. The use of angiotensin-converting-enzyme inhibitors (captopril, lisinopril) or angiotensin II receptor blockers (irbesartan, valsartan), ß-blockers (bisoprolol, carvedilol) and spironolactone along with their respective target doses were evaluated as per the European, American, and Canadian heart failure guidelines. Analyses were performed using univariate statistics. Main outcome measure The proportion of patients that was prescribed guideline-based heart failure medications along with their target doses as per guidelines. Results The overall mean age of the cohort (N = 249) was 63 ± 15 years and 61% (n = 151) were males. Seventy-one percent (n = 177) of the patients had heart failure with reduced ejection fraction while 29% (n = 72) had heart failure with mid-range ejection fraction. A total of 87% (n = 216), 62% (n = 154) and 39% (n = 96) of the patients were on ß-blockers, angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers and spironolactone, respectively. Only 33% (n = 81) of the patients were on the triple guideline-based cardiovascular medication classes concurrently. Patients with reduced ejection fraction were more likely to be prescribed the triple guideline-based cardiovascular medication classes concurrently than those that had heart failure with mid-range ejection fraction (37% vs 22%; p = 0.027). A total of 100% (96/96), 56% (121/216) and 42% (64/153) of the patients were prescribed ≥ 50% of target dose for spironolactone, ß-blockers and angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers, respectively. Conclusions The use of guideline-based cardiovascular medications in heart failure patients with reduced and mid-range ejection fraction is low in Oman. They were also largely not optimally dosed at target levels.

Ameliorative Effect of Gum Acacia on Hookah Smoke-Induced Testicular Impairment in Mice.

We investigated some reproductive actions of hookah smoke (HS) exposure (30 min/day, for 30 days) in male mice, and the possible mitigative effect of the prebiotic agent gum acacia (GA) thereon. Control mice were air-exposed (AE). Twenty-four hours after the last exposure, the levels of some plasma reproductive hormones, biochemical markers of inflammation, oxidative and nitrosative stress and testicular histopathology were assessed. The urinary level of cotinine, a major nicotine metabolite, was also measured. HS exposure induced significant decreases in testosterone, estradiol, luteinizing hormone, and androgen binding protein, as well as glutathione reductase activity and levels of nitrite and total nitrite. Plasma inhibin B, alkaline phosphatase, lipopolysaccharide binding protein, uric acid, lactate dehydrogenase, lipid peroxidation, 8-oxo-2'-deoxyguanosine, and cytochrome C were significantly increased following HS exposure. In testicular homogenate, nuclear factor-κB (NF-ĸB), nuclear factor erythroid 2-related factor 2 (Nrf2), interleukin- 6 (IL-6), interleukin-1ß (IL-1ß), transforming growth factor-ß1(TGF- ß1), and tumor necrosis factor-α (TNF- α) were all significantly elevated, and the steroidogenic acute regulatory protein (StAR) significantly decreased. Histopathologically, there was slight impairment and disorganization of spermatogenesis. Urinary cotinine concentration was elevated significantly in the HS-exposed group compared with the air-exposed group. GA co-administration mitigated the adverse actions of HS measured. In conclusion, daily exposure to HS at the above dose induced adverse actions on the reproductive system of male mice. GA co-administration significantly mitigated these effects by reducing the inflammation, oxidative and nitrosative stress, via a mechanism involving Nrf2, and reduction of StAR expression.

The renoprotective effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on adenine-induced kidney disease in rats.

We assessed the effect of treatment with the dipeptidyl peptidase-4 inhibitor, sitagliptin, on adenine-induced chronic kidney disease (CKD). Six equal groups of rats were given either normal food or food mixed with adenine (0.25% w/w for five weeks) to induce CKD. Some of these groups were also simultaneously treated with sitagliptin (2.5 and 10 mg/kg/day, by gavage). Rats given adenine showed elevation of blood pressure, decreased body weight and increased relative kidney weight. Adenine also significantly increased plasma urea, creatinine, cystatin C, liver-type fatty acid-binding protein concentrations and neutrophil gelatinase-associated lipocalin activity by 404%, 354%, 667%, 91% and 281% respectively and reduced plasma α-Klotho by 50%. In addition, adenine significantly increased albumin/creatinine ratio and N-acetyl-ß-d-glucosaminidase activity by 3553% and 400% respectively and reduced creatinine clearance by 91%. Adenine feeding also significantly elevated the plasma concentration of inflammatory cytokines (plasma tumor necrosis factor-alpha, interleukin-1beta and transforming growth factor beta-1) and significantly reduced antioxidant indices (catalase, glutathione reductase and superoxide dismutase). Histopathologically, adenine caused renal fibrosis, inflammation and atrophy. When given concomitantly with adenine, sitagliptin ameliorated all the measured adenine-induced physiological and biochemical changes but not the histopathological changes. Sitagliptin (10 mg/kg/day) reduced plasma urea and creatinine by 32% and 25% respectively and increased creatinine clearance by 248%. These findings suggest a renoprotective action of sitagliptin on adenine-induced CKD.

Potassium bromate-induced kidney damage in rats and the effect of gum acacia thereon.

Potassium bromate (KBrO3) is used in many countries in cosmetic and food industries. In this work, we investigated in male Sprague-Dawley rats, the effect of four graded oral doses of KBrO3 (5, 15, 45 and 135 mg/kg/day for 28 days) on renal function tests, inflammation, oxidative damage, and apoptosis, as well as on histopathology, using several traditional and novel renal injury biomarkers in plasma, urine and renal tissues. We also tested the possible ameliorative action of the renoprotective prebiotic agent gum acacia (GA) on the actions of KBrO3 when given concomitantly with it in the drinking water at a concentration of 15%w/v. Taken together, the results indicated that treatment with KBrO3 at the 45 and 135 mg/kg doses caused a significant dose-dependent nephrotoxicity, as evident by the measured renal structural and functional indices and biomarkers of toxicity. GA co-treatment significantly abated most of the indices and biomarkers of the renal toxicity caused by KBrO3, suggesting a beneficial effect and its possible inclusion in edible products where KBrO3 is still used.