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.

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. (AU)

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.

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

CONTEXT: The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. OBJECTIVE: This study examines the toxicological profiles of C. cajan leaf extracts. MATERIALS AND METHODS: The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. RESULTS: Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. CONCLUSION: Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.