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Strategies for Appropriate Selection of SGLT2-i vs. GLP1-RA in Persons with Diabetes and Cardiovascular Disease.
Dhindsa, DS, Mehta, A, Sandesara, PB, Thobani, A, Brandt, S, Sperling, LS
Current cardiology reports. 2019;(9):100
Abstract
PURPOSE OF REVIEW This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra). RECENT FINDINGS SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication. Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.
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Cardiovascular Disease in Type 2 Diabetes: A Review of Sex-Related Differences in Predisposition and Prevention.
Al-Salameh, A, Chanson, P, Bucher, S, Ringa, V, Becquemont, L
Mayo Clinic proceedings. 2019;(2):287-308
Abstract
Type 2 diabetes mellitus is a major risk factor for cardiovascular disease. However, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to sex. In recent years, large meta-analyses have confirmed that women with type 2 diabetes have a higher relative risk of incident coronary heart disease, fatal coronary heart disease, and stroke compared with their male counterparts. The reasons for these disparities are not completely elucidated. A greater burden of cardiometabolic risk in women was proposed as a partial explanation. Indeed, several studies suggest that women experience a larger deterioration in major cardiovascular risk factors and put on more weight than do men during their transition from normoglycemia to overt type 2 diabetes. This excess weight is associated with higher levels of biomarkers of endothelial dysfunction, inflammation, and procoagulant state. Moreover, sex differences in the prescription and use of some cardiovascular drugs may compound an "existing" disparity. We searched PubMed for articles published in English and French, by using the following terms: ("cardiovascular diseases") AND ("diabetes mellitus") AND ("sex disparity" OR "sex differences" OR "sex related differences" OR "sex-related differences" OR "sex disparities"). In this article, we review the available literature on the sex aspects of primary and secondary prevention of cardiovascular disease in people with type 2 diabetes, in the predisposition to cardiovascular disease in those people, and in the control of diabetes and associated cardiovascular risk factors.
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A review of interventions ≥ 6 months by pharmacists on adherence to medicines in cardiovascular disease: Characteristics of what works and what doesn't.
Doggrell, SA
Research in social & administrative pharmacy : RSAP. 2019;(2):119-129
Abstract
BACKGROUND Nonadherence to cardiovascular medicines occurs in 60% of subjects with chronic cardiovascular disease and leads to poor outcomes. In an attempt to improve adherence and cardiovascular outcomes, interventions are often used. Interventions may involve a pharmacist, but it is not always clear whether these are effective. OBJECTIVES The primary objective of this review is to determine whether interventions by pharmacists, alone, discussing adherence to medicines, improve adherence to medicines for cardiovascular disease. Subsequently, the review links the characteristics of the individual studies with effectiveness or lack of effect. The second objective of this review is to consider whether any improvement in adherence with interventions by pharmacist is associated with better clinical outcomes. METHODS A literature search of PubMed and CINAHL for 'pharmacist', 'medicine' with 'adherence' or 'compliance' or 'persistence' was undertaken. To be included in this review, papers had to be of a pharmacist working alone and in person in an intervention of subjects with hypertension, hyperlipidemia (prior to or after a coronary artery event) or heart failure. The paper had to be published in a peer review journal, with a measure of adherence to medicines. The effectiveness of the intervention had to be evaluated after ≥6 months. RESULTS Only 3 out of 8 interventions by pharmacists in hypertension, and 5 out of 12 interventions in subjects with hyperlipidemia led to improved adherence to medicines. In contrast, all 6 interventions by a pharmacist in subjects with heart failure were successful in improving adherence. One characteristic of successful interventions by pharmacists to improve adherence to cardiovascular medicines is that they must be more than brief/single interventions. A second characteristic is that the intervention should not involve subjects who are already highly adherent, as it is unlikely adherence can be improved in this population. Only 2 of 3 successful interventions in hypertension were associated with small reductions in blood pressure, and only one intervention in hyperlipidemia was shown to decrease LDL-cholesterol to a small extent. In subjects with heart failure, 5 of the 6 successful studies of the successful interventions by pharmacists to increase adherence also showed improved clinical outcomes. CONCLUSIONS When planning an intervention to improve adherence to medicines and cardiovascular outcomes in subjects with hypertension or hyperlipidemic, by a pharmacist alone, or as part of a multi-faceted interventions, it is essential to use an intervention that has been shown to be effective, as most interventions are not effective at improving adherence or only improve adherence and clinical outcomes to a small extent. In heart failure, there is well documented evidence of interventions by pharmacists that do improve clinical outcomes, which should be adopted widely.
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Is Heart Failure with Preserved Ejection Fraction a Kidney Disorder?
Shah, KS, Fang, JC
Current hypertension reports. 2019;(11):86
Abstract
PURPOSE OF REVIEW Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome of exertional intolerance, cardiac dysfunction, and fluid overload and is associated with significant morbidity and mortality. RECENT FINDINGS As our understanding of this syndrome has evolved, we are beginning to recognize the similarities and associations with chronic kidney disease (CKD). Salt and fluid retention are common in CKD and may be the sentinel event leading ultimately to the syndrome of HFpEF. Mechanisms linking both disease states include hypervolemia, inflammation, and endothelial dysfunction, which are also common to comorbidities that drive both HFpEF and CKD. In this review, we will discuss recent clinical research focusing on HFpEF, CKD, and comorbidities including hypertension and diabetes mellitus. We will review strategies for volume management and novel therapeutic approaches with new classes of drugs, including sodium-glucose cotransporters and angiotensin receptor/neprilysin inhibitors, which may work through targeting of both the heart and the kidney. Lastly, we emphasize why focusing on the alleviation of factors provoking renal injury and slowing the progression of renal dysfunction may provide the most therapeutic benefit in patients who have been diagnosed with HFpEF.
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Update on the ECG component of the CiPA initiative.
Vicente, J
Journal of electrocardiology. 2018;(6S):S98-S102
Abstract
The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is validating a new paradigm for assessing proarrhythmic potential of drugs that goes beyond hERG block and QT prolongation. Based on in vitro data of the drug's effects on multiple cardiac ion channel currents, CiPA's in silico model of the human cardiomyocyte will classify drugs as low, intermediate or high risk for torsade de pointes. Under CiPA, early phase 1 ECG data will be used to determine if there are unexpected ion channel effects in humans compared to the in vitro ion channel data. CiPA's ECG biomarker working group identified the heart rate corrected J-Tpeak interval (J-Tpeakc, from the end of the QRS to the peak of the T-wave) as the best of 12 ECG biomarkers to detect late sodium current block in presence of hERG block. While predominant hERG blockers prolonged QTc and J-Tpeakc, "balanced" ion channel blocking drugs (hERG + late sodium and/or calcium block) prolonged QTc without prolonging J-Tpeakc. This manuscript reviews the ECG component of CiPA and provides a description of the ECG methods used in the CiPA ECG validation clinical study.
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Drug therapies in chronic heart failure: a focus on reduced ejection fraction.
Bolam, H, Morton, G, Kalra, PR
Clinical medicine (London, England). 2018;(2):138-145
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Abstract
There are multiple evidence-based drug treatments for chronic heart failure (HF), both disease-modifying agents and those for symptom control. The majority of the evidence base supports drugs used in HF with reduced left ventricular ejection fraction. The mainstay of disease modification involves manipulation of neurohormonal activation that occurs in HF. In addition to established angiotensin-converting enzyme inhibitors, beta blockers and mineralocorticoid receptor antagonists (MRAs), newer agents are now available such as the angiotensin receptor neprilysin inhibitors. Achieving the optimal drug regimen is complex and best performed by a specialist heart failure team. We aim to provide a comprehensive overview of contemporary drug therapies in chronic heart failure, as well as practical guidance for their use. There is a focus on treating patients with challenging comorbidities such as hypotension and chronic kidney disease (CKD), where a thorough understanding of drug therapy is essential. Multiple trials assessing the benefits of new therapies in HF, such as intravenous iron, are also ongoing.
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"Fast Track" Development and Approval Process for Heart Failure Therapeutics.
Papadimitriou, L, Butler, J
Clinical pharmacology and therapeutics. 2017;(2):184-186
Abstract
Heart failure (HF) is a global epidemic, with a high mortality and morbidity burden. In such diseases, earlier access to lifesaving therapeutic regimens is imperative, and could be accomplished by improving the drug development and approval process, without jeopardizing patient safety. The US Food and Drug Administration (FDA) has already established mechanisms facilitating the latter, but further guidance to enhance and expedite the process holds promise to further improve patient outcomes.
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Optimal Low-Density Lipoprotein Cholesterol for Cardiovascular Prevention: How Low Should We Go?
Anderson, TJ
The Canadian journal of cardiology. 2017;(3):405-408
Abstract
The treatment of dyslipidemia with lifestyle interventions and statin-based therapy has been an important defense against atherosclerotic cardiovascular disease and its complications. It has been well documented for more than 2 decades that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) reduce the risk of events. The evolution of drug development and randomized clinical trials in cardiovascular medicine has resulted in the conclusion that lower cholesterol concentrations result in greater benefit. However, how aggressive one should be in lowering cholesterol levels and to what level has not been definitively established. In this brief review I aim to defend the hypothesis that lower is better on the basis of the evidence to date. This will include indirect evidence from randomized clinical trials with statins and novel lipid-modifying drugs. In addition, there is a wealth of epidemiology and Mendelian randomization genetic data to support this. Also, on-treatment low-density lipoprotein cholesterol concentrations show a robust relationship with cardiovascular disease events. Finally, most national guidelines groups around the world continue to advocate for a treat to target philosophy. As such, the prevailing philosophy is that lowering low-density lipoprotein cholesterol to very low levels is our best preventative strategy particularly for those at the highest risk. We eagerly await the results of ongoing clinical trials that will more firmly establish if this concept will ultimately be proven correct.
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Medical management of claudication.
Ratchford, EV
Journal of vascular surgery. 2017;(1):275-280
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Abstract
Peripheral artery disease (PAD) is common and associated with significant morbidity and mortality. Optimal medical management of PAD is required for each patient, irrespective of the decision regarding lower extremity revascularization. The goals include reducing cardiovascular morbidity and mortality and improving quality of life. The approach should consist of aggressive and individualized risk factor modification including smoking cessation, antiplatelet therapy, a statin, and an angiotensin-converting enzyme inhibitor. Exercise is critical for cardiovascular health and highly effective for improving claudication symptoms. Cilostazol may be considered for symptomatic treatment in certain patients.
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Emerging pharmacologic and structural therapies for hypertrophic cardiomyopathy.
Philipson, DJ, DePasquale, EC, Yang, EH, Baas, AS
Heart failure reviews. 2017;(6):879-888
Abstract
Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients. In recent years, there has been a relative surge in the development of innovative therapeutics, which aim to target the complex molecular pathophysiology and resulting hemodynamics that underlie hypertrophic cardiomyopathy. Herein, we review the new and emerging therapeutics for hypertrophic cardiomyopathy, which include pharmacologic attenuation of sarcomeric calcium sensitivity, allosteric inhibition of cardiac myosin, myocardial metabolic modulation, and renin-angiotensin-aldosterone system inhibition, as well as structural intervention by percutaneous mitral valve plication and endocardial radiofrequency ablation of septal hypertrophy. In conclusion, while further development of these therapeutic strategies is ongoing, they each mark a significant and promising advancement in treatment for hypertrophic cardiomyopathy patients.