ESSENS dyslipidemia: A placebo-controlled, randomized study of a nutritional supplement containing red yeast rice in subjects with newly diagnosed dyslipidemia

AbstractObjectiveEvidence suggests prolonged exposure to lower levels of low-density lipoprotein cholesterol (LDL-C), starting at a younger age, substantially lowers cardiovascular (CV) risk. Accordingly, the CV pandemic affecting younger population in low- to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products, as nutritional intervention is generally preferred in these cultures. However, the safety and efficacy of such preparations have not been systematically tested.MethodsIn this multicenter, double-blind study, 191 statin-free subjects with newly-diagnosed hyperlipidemia (LDL-C >120 mg/dL, 3.11 mmol/L) and no evidence of CV disease were randomized to one capsule of a proprietary bioactive phytonutrient formulation containing red yeast rice, grape-seed, niacinamide, and folic acid (RYR-NS) or matched placebo twice daily, along with lifestyle modification, for 12 wk.ResultsMean baseline LDL-C levels were 148.5 ± 24.0 mg/dL (3.85 ± 0.62 mmol/L) and 148.6 ± 21.9 mg/dL (3.85 ± 0.57 mmol/L) in the RYR-NS and placebo groups respectively. Compared with placebo, RYR-NS resulted in a significant reduction in LDL-C (−29.4% versus −3.5%, P < 0.0001) and non–high-density lipoprotein cholesterol (non-HDL-C; −29.8% versus −10.3%, P < 0.0001) at 12 wk. With RYR-NS, 43.4% individuals attained desirable LDL-C levels and 55.4% desirable non-HDL-C levels by week 12, compared to only 0% and 1.1%, respectively, at baseline. No safety issues were observed.ConclusionThis study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 wk, with magnitude of LDL-C reduction being comparable to that seen with moderate-intensity statin therapy. Further long-term studies are required to determine the impact of RYR-NS on treatment adherence and clinical outcomes

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Indian registry on current patient profiles & treatment trends in hypertension (RECORD): One year interim analysis

Background & objectives: In India, hypertension constitutes a significant health burden. This observational, non-interventional, prospective study was conducted in five centres across India to evaluate the current clinical practices for the management of hypertension. Methods: Participants were enrolled if they were newly diagnosed with essential hypertension or had pre-existing hypertension and were on the same therapeutic plan for the previous three months. At baseline, three months, six months, and one year, information on the patient and their treatment regimen was documented, and their quality of life (QoL) was evaluated. Results: A total of 2000 individuals were enrolled in this study, with a mean age of 54.45 yr. Of these, 55.7 per cent (n=1114) were males, and 957 (47.85%) were newly diagnosed with hypertension, while 1043 (52.15%) had pre-existing hypertension. Stage 2 hypertension (systolic blood pressure (BP) >140 or diastolic BP ≥90 mmHg) accounted for more than 70 per cent of the participants (70.76% of pre-existing and 76.29% of newly diagnosed); the average duration of pre-existing hypertension was 68.72 months. Diabetes (31.6%) and dyslipidaemia (15.8%) were the most common comorbidities. In 43.3 per cent of the participants, monotherapy was used, and in 56.7 per cent (70.55% fixed-dose combination), combination therapy was used. Telmisartan (31.6%), amlodipine (35.2%), and a combination of the two (27.1%) were the most commonly prescribed treatment regimens. At three months, six months, and one year, treatment modifications were observed in 1.4, 1.05, and 0.23 per cent of the participants receiving monotherapy and 2.74, 4.78 and 0.35 per cent receiving combination therapy, respectively. In both groups, the proportion of individuals with controlled hypertension (≤140/90 mmHg) increased by more than 30 per cent after a year. At one year, physical and emotional role functioning, social functioning, and health improved considerably. Interpretation & conclusions: Combination therapy for hypertension is increasingly preferred at the time of initial diagnosis. The efficacy, safety, and tolerance of the recommended medications were reflected by improvements in the QoL and the minimal changes in the therapeutic strategy required

Alcohol septal ablation for hypertrophic obstructive cardiomyopathy – 8 years follow up

Background: Alcohol septal ablation is emerging as an alternative to surgical myectomy in the management of symptomatic cases of Hypertrophic obstructive cardiomyopathy (HOCM). This involves injection of absolute alcohol into 1st septal perforator thereby producing myocardial necrosis with resultant septal remodelling within 3–6 months. This results in reduction of septal thickness and LV outflow gradients with improvement in symptoms. Methods: Fifty three patients had undergone alcohol septal ablation, there were 2 early and 2 late deaths and 4 patients lost to follow up. Forty-five (85%) of them were followed up to a mean period of 96 ± 9.2 months. Clinical, ECG, and Echocardiographic parameters were evaluated during follow up. Results: Only 4 out of 51 patients remained in NYHA class III or IV at the end of 6 months. Significant reduction of LV outflow gradients (79 ± 35 to 34 ± 23 mmHg) and septal thickness (23 ± 4.7 mm to 19 ± 3 mm) were observed during 6 months follow up. Beyond 6 months there was no further decrease in either septal thickness or LVOT gradients noted. Ten percent of patients needed pacemaker implantation. There was 92% survival at the end of 8 years. Conclusion: Alcohol septal ablation is a safe and effective nonsurgical procedure for the treatment of HOCM. By minimizing the amount of alcohol to ≤2 ml, one can reduce complications and mortality. The long-term survival is gratifying

Clinical recommendations to diagnose and monitor patients with transthyretin amyloid cardiomyopathy in Asia

10.1002/clc.23882Clinical Cardiolog

Efficacy and tolerability of fixed dose combination of metoprolol and amlodipine in Indian patients with essential hypertension

Background: This open-labeled, post-marketing study was conducted to assess the efficacy and tolerability of fixed dose combination of amlodipine and metoprolol extended release capsules in mild to moderate hypertension in adult Indian patients. Materials and Methods: Of 101 enrolled patients, 64 drug naοve patients were treated with regimen A (amlodipine 5 mg + metoprolol 25 mg) and those with prior history of hypertension ( n = 37) were treated with regimen B (amlodipine 5 mg + metoprolol 50 mg) for 8 weeks. Treatment response was assessed at week 4 and 8. Dose up titration to regimen B was carried out for those who failed to achieve the target blood pressure (BP) at week 4 in regimen A and additional antihypertensives were added to those in regimen B. Safety laboratory tests were performed at baseline and end of study. Results: Mean age (±SD) of patients was 53.36 (±11.26) years and body weight (±SD) 63.40 (10.03) kg. Ninety five patients (94.06%) were only hypertensive and 6 (5.94%) had hypertension with history of coronary artery disease; mean duration (±SD) of hypertension was 42.50 (48.07) months. At baseline, patients had a mean (±SD) systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 154.98 (±7.76) mmHg and 95.55 (±5.70) mmHg respectively. There was a statistically significant ( P < 0.001) reduction of 12.16% and 14.69% in SBP, 11.49% and 14.65% in DBP at week 4 and week 8 respectively, compared to baseline. Normalization of overall BP was achieved in 49.49% and 70.71% patients at week 4 and 8, respectively. Peripheral edema was reported in 2.97% (3/101) patients. Conclusion: This combination was safe, efficacious, and well-tolerated in study population