Eicosapentaenoic Acid for Cardiovascular Events Reduction- Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Randomized clinical trials (RCTs) investigating the impact of omega-3-fatty acid supplementation on cardiovascular events have largely shown no benefit. However, there is debate about the benign nature of the placebo in these trials. We aimed to conduct a network meta-analysis of RCTs to compare the outcomes of omega-3 fatty acid supplementation to various placebo oils. METHODS: MEDLINE and EMBASE were searched through May, 2021 to identify RCTs investigating cardiovascular outcomes with omega-3-fatty acid formulations [eicosapentaenoic acid (EPA), decosahexanoic acid (DHA), or the combination] versus placebo or standard of care controls. RESULTS: Our analysis included 17 RCTs that enrolled a total of 141,009 patients randomized to EPA (n=13,655), EPA+DHA (n=56,908), mineral oil placebo (n=5,338), corn oil placebo (n =8,876), olive oil placebo (n=41,009), and controls (no placebo oil; n=15,223). Rates of cardiovascular death [hazard ratio (HR) (95% confidence interval, CI) =0.80 (0.65-0.98); p =0.033], myocardial infarction [HR (95% CI) =0.73 (0.55-0.97); p=0.029] and stroke [HR (95% CI) =0.74 (0.58-0.94); p=0.014] were significantly lower in those receiving EPA compared to those receiving mineral oil, but were not different from rates in those receiving other oils or controls. Rates of coronary revascularization were significantly lower in those receiving EPA than in those receiving either EPA+DHA, mineral oil, corn oil, or olive oil placebo, but not controls. All-cause death was similar among all groups, but combined EPA+DHA was associated with reduced risk of cardiovascular death compared to controls [HR (95%CI): 0.83 (0.71-0.98)]. CONCLUSIONS: Our analyses demonstrate that although EPA supplementation lowers risk of coronary revascularization more than other oils, there may not be a benefit relative to standard of care. Further, EPA reduces the risk of cardiovascular events only in comparison to mineral oil and not when compared with other placebo oils or controls. In contrast, combined EPA+DHA was associated with reduced risk of cardiovascular death compared to controls.

Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation.

OBJECTIVES: The objectives of the study were to compile and summarize the data from all of the clinical trials designed to examine the association between haptoglobin (Hp) genotype and incidence of cardiovascular (CV) events in patients with diabetes mellitus (DM) and to assess the impact of vitamin E treatment on CV outcomes according to the Hp genotype. BACKGROUND: The Hp genotype could serve as a predictive biomarker to DM patients who may benefit from vitamin E therapy. METHODS: The electronic databases MEDLINE, PubMed, EMBASE and the Cochrane Library for Central Register of Clinical Trials were searched systematically using the following MESH terms: "haptoglobin genotype", "diabetes mellitus" and "cardiovascular events". RESULTS: Overall, 13 studies fit the inclusion criteria for this analysis, yielding a large study population that included 6,161 patients without Hp 2-2 and 4,684 patients with Hp 2-2. The analysis of these studies showed that the incidence of CV events in DM patients with the Hp 2-2 genotype was significantly increased as compared to non-Hp 2-2 patients in all three subgroups of case-control (OR: 2.2, 95% CI: 1.3-3.6; P=0.003), cohort (OR: 1.3, 95% CI: 1.2-1.5; P=0.001) and randomized controlled trials (OR: 1.6, 1.2-2.2; P=0.005). Among patients with the Hp 2-2 genotype, administration of vitamin E was associated with lower rates of CV events (OR: 0.66, 95% CI: 0.45-0.95; P=0.025). Further investigation into the association between Hp 2-2 and myocardial infarction, stroke, mortality and end-stage renal disease was also performed. CONCLUSION: The Hp genotype is a risk factor for CV events in patients with DM, and administration of vitamin E appears to offer a low cost and accessible means of reducing CV events and mortality in this population.

Burden of arrhythmias in peripartum cardiomyopathy: Analysis of 9841 hospitalizations.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is associated with significant morbidity and mortality. Arrhythmogenic causes of death have been implicated in a significant number of patients. However, there is a dearth of systematic studies evaluating the burden of arrhythmias in PPCM. METHODS: We used the Healthcare Utilization Project, Nationwide Inpatient Sample database (2007-2012) and identified 9841 hospitalizations for women aged ≥18years with a primary diagnosis of PPCM. Frequency of arrhythmias, utilization of electrophysiologic procedures, length of stay, hospitalization costs and outcomes associated with arrhythmias were determined. RESULTS: Mean age was 30.05±6.69years. Arrhythmias were present in 18.7% of hospitalized PPCM cohort. Ventricular tachycardia was the most common arrhythmia and was noted in 4.2%. Approximately 2.2% of cases experienced cardiac arrest. Electrical cardioversion was performed in 0.3%, Catheter ablation in 1.9%, PPM implantation in 3.4% and ICD in 6.8% of hospitalizations for PPCM with arrhythmias. In-hospital mortality was 3-times more frequent in arrhythmia cohort (2.1% vs. 0.7%). Hospitalization costs were significantly higher in PPCM with arrhythmias. Elixhauser comorbidity score (adjusted OR:1.10; 95%CI:1.02-1.18; p=0.016), in-hospital mortality (adjusted OR:2.35; 95%CI:1.38-4.02; p=0.002), cardiogenic shock (adjusted OR:2.61; 95%CI:1.44-4.72; p=0.002), utilization of balloon pump (adjusted OR:13.4; 95%CI: 2.55-70.53; p<0.001), Swan-Ganz catheterization (adjusted OR:3.12; 95%CI:1.21-8.06; p=0.019), and coronary angiography (adjusted OR:1.79; 95%CI:1.19-2.70; p=0.005) were significantly associated with arrhythmias in PPCM. CONCLUSIONS: Arrhythmias were present in 18.7% of PPCM related hospitalizations. Morbidity, in-hospital mortality, length of inpatient stay, hospitalization costs and cardiac procedure utilization were significantly higher in the arrhythmia cohort.

The future of interventional management of hypertension: threats and opportunities.

In about 48% hypertensive patients in the United States, blood pressure remains higher than accepted treatment targets despite broad availability of effective pharmaceutical agents. Of these 48%, recent estimates define about 10-11% have treatment-resistant hypertension (TR-HTN). Compensatory changes in sympathetic nervous system function are an important component of HTN. Recent technical advances targeting the sympathetic activity of the carotid sinuses (Baroreflex Activation Therapy-BAT) and the renal sympathetic nerves (Renal Denervation Therapy-RDT) have renewed interest in invasive therapy for the treatment of drug-resistant hypertension. Encouraging results from the recent Rheos Pivotal and Symplicity HTN-2 trials on the safety and efficacy of BAT and RDT respectively, indicate that invasive approaches can safely reduce blood pressure in patients with resistant hypertension. The main goal of this article is to review the results of preclinical and clinical studies on the electric stimulation of the carotid sinus and the catheter-based renal denervation.

Efficacy of baroreflex activation therapy for the treatment of resistant hypertension.

The contribution of sympathetic activation in the development of hypertension is supported by early experimental evidence based on surgical denervation of sino-aortic baroreceptors or lesions of the central relay station of the baroreflex, the nucleus tractus solitarii. Disruption of this area of the brain was associated with an immediate increase in blood pressure. Sympathetic overactivity can also be triggered by impairment of the inhibitory function physiologically exerted by reflexogenic areas (arterial baroreceptors, cardiopulmonary receptors, and chemoreceptors) on adrenergic drive. Metabolic and humoral mechanisms are also thought to be involved in the development and progression of hypertension-related sympathetic overdrive.

The OSCAR for cardiovascular disease prevention in chronic kidney disease goes to blood pressure control.

Nephropathy progression is slowed and cardiovascular events reduced in patients with stage 3 or higher chronic kidney disease when blood pressure is controlled using combinations of renin-angiotensin system (RAS) blockers with dihydropyridine calcium channel blockers or diuretics. We discuss a trial comparing high-dose RAS blockade with lower-dose RAS blockade combined with a dihydropyridine calcium channel blocker. The primary outcome was cardiovascular events. The combination group had better blood pressure control and fewer total events.

Timing and efficacy of alternative methods of sympathetic blockade.

Despite the presence of seven different antihypertensive drug classes and over 120 different antihypertensive medications, about 48 % of the 75 million people with hypertension are not reaching their target blood pressure goals. One of the reasons for this lack of control is the failure to adequately inhibit the sympathetic nervous system. Consequently, alternative therapies have been attracting interest. Recent technical advances targeting the sympathetic over-activity of the carotid sinuses (baroreflex activation therapy, BAT) and the renal sympathetic nerves (renal denervation therapy, RDT) have renewed interest in invasive therapies for the treatment of drug-resistant hypertension. Encouraging results from the recent Rheos Pivotal and Symplicity HTN-2 trials on the safety and efficacy of BAT and RDT, respectively, indicate that invasive approaches can safely reduce blood pressure in patients with resistant/refractory hypertension. These approaches, while still experimental in the US, are appropriate for those on more than three fully tolerated doses of antihypertensive medications whose blood pressure is not at goal, i.e. <140/90 mmHg. The present review is focused on the clinical implications of these two technics and when they are appropriate.