Dr. Shivam Patel has graduated from Lake Erie College of Osteopathic Medicine (LECOM) School of Pharmacy with a Doctor of Pharmacy degree. Completed PGY1 Pharmacy Residency at Martinsburg VA Medical Center. Currently Dr. Patel is continuing to serve veterans as a Clinical Pharmacist.

Shivam Patel, Pharm.D.

The use of beta blockers for rate control in patients with atrial fibrillation (AF) and heart failure (HF) has shown mortality benefits. A study performed by Fauchier et al. found that there was a reduction of 40% with the use of beta blockers in patients that have AF and HF.

Current recommendation of beta blockers in patient with HF include bisoprolol, carvediol, or metoprolol succinate. Metoprolol tartrate may provide better rate control with twice daily dosing.

Patients with AF that received carvedilol had an improvement in left ventricular end diastolic (p = <0.001), end-systolic dimensions (P = <0 .0001), and ejection fraction (P =<0 .0001) compared to patients who received metoprolol, which showed decreased end-systolic dimensions (P =0 .07), and increase in ejection fraction (P =0 .05). 

The Carvedilol or Metoprolol European Trial (COMET)

, a randomized double blind trial, looked into the comparison of metoprolol tartrate and carvedilol in patients with HF. Carvedilol was shown to have  beneficial effects on mortality (RR 0.836: CI 0.74—0.94; P=0.0042).

 A prognostic relevance analysis of AF was performed on patients that were a part of COMET. Patients with HF were randomized to receive carvedilol or metoprolol tartrate. AF was associated with increased mortality (RR 1.29: 95% CI 1.12—1.48; P=<0.0001), and higher all cause death or hospitalization (RR 1.25: CI 1.13–1.38; P= <0.0001).

 The authors concluded that carvedilol, compared to metoprolol, offers additional benefits among patients with AF.

A randomized trial performed by Fung J et al. compared the effectiveness of carvedilol and metoprolol tartratein patients with HF and AF.

 The study found that both treatment options had an equal improvement in left ventricular systolic function in HF with AF.

 These results were similar to those presented in other trials, such as the US Carvedilol Heart Failure Trials Program.

While there was no direct study regarding the use of metoprolol tartrate in a patient population involving HF and AF, many HF studies had a subgroup of patients who had concomitant AF that required assessment. One aspect of these studies to take into consideration would be the amount of patients that were assessed. A certain percentage of patients had HF and were in AF in many of the studies.

The overall conclusion is that the use of beta blocker therapy in patients with HF and AF has shown mortality benefit and would be recommended for use in management of patient’s care. Whether metoprolol tartrate would be preferred over carvedilol or other preferred beta blockers in patients with HF and AF, could not be determined.

Fauchier L, Grimard C, Pierre B et al. Comparison of Beta Blocker and Digoxin Alone and in Combination for Management of Patients With Atrial Fibrillation and Heart Failure. 

Meng F, Yoshikawa T, Baba A et al. B-Blockers Are Effective in Congestive Heart Failure Patients With Atrial Fibrillation

 Vol. 9 No. 5 2003. doi:10.1054/S1071-9164(03)00127-1

Poole- Wilson PA, Swedberg K, Cleland JG et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. 

Swedberg, K, Olsson L, Charlesworth A et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. 

 Issue: Volume 26(13), July 2005, pp 1303-1308. DOI: 10.1093/eurheartj/ehi166

Fung J, Chan S, Yeung L, et al. Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials

Articles

Metoprolol Tartrate Use in Patients with Congestive Heart Failure and Atrial Fibrillation

Both semaglutide and dulaglutide are in a glucagon-like peptide 1 (GLP-1) receptor agonist class of medications used in treatment of type 2 diabetes. GLP-1 receptor agonists reduce blood glucose by stimulating insulin secretion and reducing glucagon secretion, both occurring in a glucose dependent manner.

 This property provides a lower risk of hypoglycemia. These types of medications also delay gastric emptying in the early postprandial phase thus resulting lower blood glucose levels. A secondary outcome of delay gastric emptying may also result in reduction in body weight.

Semaglutide and Dulaglutide both have contraindication of a personal or familial history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).

 Incidence of thyroid C-cell tumors occurred in animal studies, though currently it is unknown whether MTC have occurred in humans. European Union prescribing information for GLP-1 receptor agonists does not include contraindication of personal or family history of MTC or MEN 2.

When looking at warnings and precautions of semaglutide and dulaglutide, 1 difference is noted in labeling: dulaglutide does not include precaution of retinopathy. Incidence of diabetic retinopathy was reported in SUSTAIN 6 trial, which was a cardiovascular outcomes trial for semaglutide. Semaglutide was associated with increased risk of diabetic retinopathy vs placebo.

 The lack of diabetic retinopathy in labeling for dulaglutide may be due to studies not including the safety outcome or listed as exclusion in criteria.

Both semaglutide and dulaglutide are dosed once weekly for treatment of type 2 diabetes. The recommended dose of dulaglutide is 0.75mg weekly and may be increased up to 1.5mg weekly.

Semaglutide is dosed 0.25mg weekly for 4 weeks. The 0.25mg weekly dose is considered an initiation dose and not effective for appropriate glycemic control.

 Semaglutide should be increased to 0.5mg weekly after initiation is finished. If additional glucose control is warranted, semaglutide can be increased to 1mg weekly after 4 weeks of 0.5mg weekly.

Hemoglobin A1c (HbA1c) reduction for both medications were similar. Comparison trial SUSTAIN 7 investigated semaglutide vs dulaglutide. Semaglutide had a higher HbA1c reduction in comparison to dulaglutide (-1.4 vs -1.1 respectively, p=0.002) with comparing dulaglutide 0.75mg and semaglutide 0.5mg.

 A higher percentage of patients were able to achieve hba1c <7% at week 40 with semaglutide 0.5mg (65% vs 51%, p=<0.0001).

Semaglutide and dulaglutide have similar efficacy results. A difference is noted when considering precautions. The difference of diabetic retinopathy listed for semaglutide and not listed for dulaglutide may impact clinical decision making when prescribing medications. Though a patient history including retinopathy does not exclude a patient from using semaglutide. Patients with history of diabetic retinopathy should be monitored for progression of diabetic retinopathy with the use of semaglutide.

National Library of Medicine. Semaglutide. Drug Label Information. 

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79

 Updated January 16, 2020. Accessed February 6, 2020.

National Library of Medicine. Dulaglutide. Drug Label Information. 

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=463050bd-2b1c-40f5-b3c3-0a04bb433309

 Updated September 26, 2019. Accessed February 6, 2020

Romera, I., Cebrián-Cuenca, A., Álvarez-Guisasola, F. et al. A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes. 

 10, 5—19 (2019) doi:10.1007/s13300-018-0535-9

Vilsboll T, Bain SC, Leiter LA et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. 

. 2018 Apr;20(4):889-897. doi: 10.1111/dom.13172

Novo Nordisk. Ozempic vs Trulicity SUSTAIN7. Ozempic website. 

https://www.ozempicpro.com/clinical-data/ozempic-vs-trulicity.html

 Reviewed January 2020. Accessed February 6, 2020

Both semaglutide and dulaglutide are dosed once weekly for treatment of type 2 diabetes.

Comparing Semaglutide Versus Dulaglutide

Medical professionals everywhere are fully supporting the benefits of exercise. The American College of Sports Medicine and American Diabetes Association state aerobic exercise and resistance training together can efficiently lower body weight, decrease cardiovascular risk factors, reduce disease progression, improve mood and so much more.

It is a cornerstone of patient self-treatment for many acute and chronic disease processes across the spectrum. However, a new and up-and-coming theorem is that exercise can decrease addiction, substance abuse, and therefore prevent imminent bad outcomes. A study published in 

 looked at the effects of acute exercise on drug cravings, mood, and self-esteem, and presented preliminary findings. The study concluded that football, circuit training, and walking are feasible therapeutic activities for inpatients with poly-substance dependence.

One big limitation of this study was that it was performed in a select group of patients, and further randomized controlled studies would have to be performed to determine long-term effects.

In addition to risk reduction, aerobic exercises such as running and weight lifting have shown to improve psychological imbalances.

Increased intensity aerobic exercises decrease down-regulation of activity in the prefrontal cortex. This area is often up-regulated in anxiety and depression. Many nicotine users state they use tobacco products to curb the effects of their anxiety. Exercise has been shown to decreased nicotine withdrawal and cravings with increased levels of exercise. When comparing steady-state running and anaerobic sprint training, the latter has been found to increase levels of dopamine and brain-derived neurotropic factor (BDNF).

Findings from preclinical studies have hypothesized that BDNF is increased by exercise and serves as a substitute reward for drug intake by increasing dopaminergic activity.

Evidence shows aerobic exercise can change the mesolimbic pathway, altering seeking and addiction behaviors in substance users.

This alteration is theorized to be mediated by decreased binding of the dopamine type 1-like and dopamine type 2-like receptors.

The evidence regarding use of forms of exercise and impact on drug cravings and substance use disorders is limited. Given the limited evidence available, further exploration in this theory may impact the lives of many in a multifactorial way. Exercise improves psychological, behavioral, neurobiological, and overall health of patients. The overall safety profile of this treatment does more benefits than harm in most cases.

This provides pharmacist and other health care professionals another opportunity to provide counseling regarding this possibility as this approach may have a multifactorial impact.

Ellingsen MM, Johannesen SL, Martinsen EW et al. Effects of acute exercise on drug craving, self-esteem, mood and affect in adults with poly‐substance dependence: Feasibility and preliminary findings. 

. Volume 37, Issue 6. 04 June 2018. doi.org/10.1111/dar.12818

Colledge F, Gerber M, Ludyga S et al. Anaerobic Exercise Training in the Therapy of Substance Use Disorders: A Systematic Review. 

. 04 December 2018. doi.org/10.3389/fpsyt.2018.00644

Robison LS, Swenson S, Hamilton J et al. Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction. 

Medicine and Science in Sports and Exercise

Linke SE, Ussher M. Exercise-based treatments for substance use disorders: evidence, theory, and practicality. 

The American Journal of Drug and Alcohol Abuse

Exercise improves psychological, behavioral, neurobiological, and overall health of patients.

Exercise: Another Potential Option for Substance Abuse Disorder

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death in the United States today. According to the American College of Cardiology (ACC) and American Heart Association (AHA) Task Force, managing elevated cholesterol is one of the the key elements to decreasing negative outcomes in this multifactorial disease state.

The ASCVD Risk algorithm is used to calculate a 10-year risk of heart disease or stroke and for recommendations of statin therapy. This algorithm calculates this risk by evaluating the following factors: history of ASCVD, low-density lipoprotein (LDL) cholesterol levels, age, current diagnosis of diabetes, sex, race, total cholesterol, high-density lipoprotein (HDL) cholesterol levels, medication controlled hypertension, and smoking history. Any history of the following conditions is considered a known history of ASCVD: acute coronary syndrome, myocardial infarction, stable angina, coronary revascularization, stroke, transient ischemic attack, peripheral arterial disease, or patients with very high LDL levels (>190).

Risk factors for ASCVD include smoking, dyslipidemia, diabetes, and hypertension. The cornerstone to preventing bad outcomes is focusing on a heart healthy lifestyle. According to the CDC, a heart healthy lifestyle revolves around maintaining a healthy weight, eating a well-rounded diet, exercising 3 to 5 times per week for 30-minute increments, avoiding tobacco products, and limiting alcohol use. 

Assessment of ASCVD risk is crucial for primary prevention of cardiovascular disease. For those aged 20 to 39 years, traditional risk factors such as tobacco use, hypertension, or others, can be measured to identify whether lifestyle optimization or treatment is needed.

 For adults aged 20 to 39 years and 40 to 59 years, who are not at an elevated (

 7.5%) 10-year risk, an estimation of a lifetime or 30-year risk for ASCVD can be made.

Estimating ASCVD 10-year risk can be performed using an online risk calculator provided by ACC. The 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease guidelines suggest the race and sex specific Pooled Cohort Equation to estimate 10- year ASCVD risk of asymptomatic adults ages 40 to 79 years. 

 Adults are categorized into low (<5%), borderline (5% to 7.5%), intermediate (

With the 2019 ACC/AHA guidelines for primary prevention of cardiovascular disease, statin treatment recommendations vary from previous guidelines. Patients’ aged 20 to 75 years and LDL 

 190 mg/dl use high-intensity statin without risk assessment. 

 Moderate-intensity statin can be used in patients aged 40 to 75 years and with type 2 diabetes mellitus. High intensity statin in this patient population may be considered based on risk estimation. For patients aged 40 to 75 years and with LDL 

70 mg/dl and <190 mg/dl without diabetes, use risk estimator to identify intensity of statin.

Patients on statin therapy should be assessed for compliance, therapy effectiveness, and adverse effects. Fasting lipid levels should be checked to assess effectiveness. These should be compared to values prior to statin initiation. Adverse effects are usually experiences in the first 4 to 12 weeks of starting treatment. Common adverse effects include myalgia. Certain drug-drug interactions can increase risk of patients experiencing myalgia with statins. Patients should also be screened for type 2 diabetes mellitus.

Statins and a heart healthy lifestyle are able to manage the risks of ASCVD effectively; however, there are times when additional treatments are needed. Specifically, other agents should be considered in patients with a heavy history of ASCVD events or with multiple high-risk factors. Ezetimibe is often the second-line agent added to maximized statin therapy. Additional therapy can be considered if ezetimibe and statin combination therapy do not lower the LDL-C level below 70 mg/dL. The next agent considered is a proprotein convertase subtilisin/kexin type 9 inhibitor. 

Updated 2019 guidelines by ACC/AHA for primary prevention of cardiovascular disease shows different categories of patients and respective statin intensity treatment compared with previous guidelines. Identifying appropriate risk factors and category will help with selecting the appropriate intensity statin. 

Grundy SM, Stone NJ, Bailey AL et al. 2018 Guideline on the Management of Blood Cholesterol. 

. Nov 2018. DOI: 10.1016/j.jacc.2018.11.003.

Preventing Heart Disease: Healthy Living Habits. Center for Disease Control and Prevention. 

https://www.cdc.gov/heartdisease/healthy_living.htm

 Reviewed August 10, 2015. Accessed October 17, 2019.

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 

Managing elevated cholesterol is one of the the key elements to decreasing negative outcomes in atherosclerotic cardiovascular disease.