http://creativecommons.org/licenses/by-nc/4.0/. The Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial which randomized 12,537 patients with DM, impaired glucose tolerance, or impaired fasting glucose to either insulin glargine or therapy without insulin reported a neutral effect on both initial and recurrent HF hospitalizations during a median follow-up of 6.2 years [54]. This is a selective inhibitor of phosphodiesterase type 3, antiplatelet and vasodilatory agent used primarily in patients with intermittent claudication and peripheral arterial disease [11]. In addition, the Dapagliflozin Effect on Symptoms and Biomarkers in Patients with Heart Failure (DEFINE-HF) and Dapagliflozin in Preserved Ejection Fraction Heart Failure (PRESERVED-HF), and Empagliflozin Impact on Hemodynamics in Patients with Heart Failure (EMBRACE-HF) trials will evaluate potential mechanisms of SGLT2 inhibition in patients with established HFrEF and HFpEF. Effect of contraindicated drugs for heart failure on hospitalization PMID: 12796126. An enlarged heart can lead to serious health problems such as heart failure, stroke, or even sudden death. The Osservatorio Geriatrico Regione Campania Group. From AM, Leibson CL, Bursi F, Redfield MM, Weston SA, Jacobsen SJ, et al. They are typically administered as a subcutaneous injection daily or weekly and can be given alone or in combination with other glucose-lowering agents. Singh S, Loke YK, Furberg CD. Thiazolidinediones such as Pioglitazone are associated with fluid retention. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. Allen LA, Magid DJ, Gurwitz JH, Smith DH, Goldberg RJ, Saczynski J, et al. [2] Ungprasert P, Srivali N, Kittanamongkolchai W. Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A systematic review and meta-analysis. Heart failure, also known as congestive heart failure (CHF), is not something that occurs suddenly like a heart attack. Risk of Heart Failure Hospitalization Associated With Cilostazol in Diabetes: A Nationwide Case-Crossover Study. SGLT2 inhibition lowers the threshold of saturation, thereby increasing glucose secretion in the urine. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Your heart can become enlarged when it has to work harder as a result of stress, infection, or heart disease. Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA, USA. Before Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. NSAIDs: Adverse cardiovascular effects - UpToDate These benefits, however, should be balanced by their potential risks including hypotension, genital mycotic infections, as well as lower-limb amputation and fractures (seen with canagliflozin only). The relationship between hyperglycemia and cardiovascular (CV) outcomes in patients with diabetes and HF is complex. Prevalence, clinical characteristics and outcome in patients with chronic heart failure and diabetes. Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, et al. 16 Foods That Are Bad for Your Heart Metformin therapy and prognosis of patients with heart failure and new-onset diabetes mellitus: a propensity-matched study in the community. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Kober LV, et al. The presence of DM in HF patients is associated with an increased risk of death, hospitalization, and prolonged hospital stay [19,20]. Front Pharmacol. Received 2020 Dec 15; Accepted 2021 Feb 25. Prog Cardiovasc Dis. 1 There is little evidence to support differences in effectiveness for pain treatment when comparing all NSAIDs. Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis. Both rosiglitazone and pioglitazone are associated with reduced blood pressure, increased fluid retention, and increased risk of HF [56-58]. Subsequent trials have not demonstrated an increased HF risk and recent meta-analyses have demonstrated no statistically significant increase in HF risk compared with placebo [81]. Canagliflozin and cardiovascular and renal events in type 2 diabetes. To avoid weight gain while on a heart failure diet, don't eat snacks . Erdmann E, Charbonnel B, Wilcox RG, Skene AM, MassiBenedetti M, Yates J, et al. The potential mechanisms by which SGLT2 inhibitors improve CV outcomes are undergoing investigation [99]. The Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-PRESERVED) trial has been designed to evaluate the effects of empagliflozin versus placebo on clinical outcomes in patients with HFpEF and it includes patients with and without T2DM. Mannucci E, Monami M, Di Bari M, Lamanna C, Gori F, Gensini GF, et al. Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, et al. Risk factors include Structural heart disease, e.g: MI or HF [12], Oral meds: Alendronate effervescent tablet, Sodium polystyrene sulfonate suspension, Polyethylene glycol powder for solution, erythromycin, Injection meds: Piperacillin/tazobactam, Metronidazole, Ticarcillin/clavulanate, azithromycin. Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. A system of care . There are currently four FDA approved SGLT2 inhibitorscanagliflozin, dapagliflozin, empagliflozin and ertugliflozin. [8] Kber L, Torp-Pedersen C, McMurray JJ, Gtzsche O, Lvy S, Crijns H, Amlie J, Carlsen J; Dronedarone Study Group. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Citalopram, Tricyclic antidepressants (TCA) such as amitriptyline, Imipramine etc. We avoid using tertiary references. Cosentino F, Cannon CP, Cherney DZ, Masiukiewicz U, Pratley R, Dagogo-Jack S, et al. Similarly, the Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE) trial, found similar rates of CV events and a trend towards increased rates of HF hospitalizations (106 vs. 89, P=0.22) in patients treated with alogliptin compared with placebo [76]. SGLT-2 inhibitors: a new mechanism for glycemic control. Glucagon-like peptide-1 receptor agonists and heart failure in type 2 diabetes: systematic review and meta-analysis of randomized and observational studies. A retrospective cohort study using the UK general practice research database of 91,521 patients with DM found that compared with metformin, monotherapy with firstor second-generation sulfonylureas was associated with a significant 24% to 61% increased risk for all-cause mortality (P<0.001) and second-generation sulfonylureas with an 18% to 30% increased risk for HF (P=0.01 and P<0.001, respectively) [48]. US Boxed Warning regarding Lactic acidosis: Risk factors include renal impairment, 65 years and hypoxic states, e.g: acute congestive heart failure. Commonly Used Drugs Can Cause or Worsen Heart Failure Observational studies have suggested greater CV mortality and increased HF prevalence in insulin treated patients with T2DM [52]. In heart failure, the heart can no longer pump enough blood around the body. 2007 Aug;30(8):2148-53. doi: 10.2337/dc07-0141. Initiation of treatment before the patient is discharged from the hospital so both patient and doctor are aware of what is needed and how to properly adhere to a treatment plan. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. CV outcomes of trials of glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-IV (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors are summarized in Tables 3--55. 2019 Jun 1;307:41-48. doi: 10.1016/j.toxlet.2019.02.013. Salt Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Is it not? Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K, et al. These decongestants cause constriction of the blood vessels, leading to a sudden increase in blood pressure. US Boxed Warning: Thiazolidinediones may cause or exacerbate heart failure closely monitor for signs and symptoms of HF particularly after initiation or dose increases. Epub 2003 Jun 9. official website and that any information you provide is encrypted The SGLT2 is a high-capacity, low-affinity transporter expressed almost exclusively in the initial convoluted portion of the proximal tubule of the nephron where it accounts for 90% of glucose reabsorption [82]. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. Fatigue and weakness. NSAIDs and Heart Failure: Causes and Risks Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. 12. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. No potential conflict of interest relevant to this article was reported. The CANVAS program, integrated data from two trials involving 10,142 patients with T2DM at high risk for cardiovascular disease (CVD) were randomized to canagliflozin or placebo [86]. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. 2015 Oct 13;132(15):e198. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial found an increased risk of HF death or hospitalization associated with rosiglitazone (HR, 2.10; 95% CI, 1.35 to 3.27) [60]. Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESCHFA heart failure long-term registry. PMID: 25581138. Peripheral edemamay occur in patients with or without a prior history of heart failure, which may result in acute decompensated heart failure. Symptoms of hypokalemia include muscle weakness, palpitations and muscle aches. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. In large randomized controlled trials GLP-1 receptor agonists have had mixed effects, generally demonstrating CV benefits in patients with T2DM but no apparent impact on HF hospitalizations (Table 3). Near the End, and Preparing for a New Beginning, Cardiovascular Disease in the Filipino American Community: Revisiting Our Beloved Filipino-Comfort Foods, Polycystic Ovary Syndrome was found to be associated with increased cardiovascular complications at the time of delivery, Who Am I? The type of medication people use for the treatment of heart failure will depend on the type of heart failure they have. In a scientific statement from AHA, TCA has been determined to exacerbate underlying myocardial dysfunction,2016 monitor EKG [12], Citalopram risk of dose-dependent QT prolongation ECGandtorsade de pointes(TdP) . The effects of GLP-1 receptor agonists are heterogenous and may reduce the risk of major adverse CV events and mortality in the general population of patients with T2DM. An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure. The heart is usually the size of a fist, but it has the ability to grow . After a median of 1.5 years, treatment with dapagliflozin resulted in a 26% risk reduction in HF hospitalization or CV death (HR, 0.74; 95% CI, 0.65 to 0.85). GLP-1 receptor agonists: a review of head-to-head clinical studies. While the CAROLINA study had a relatively low prevalence of HF (4.5%) it did not find a significant difference on major adverse CV events or HF hospitalizations in patients treated with linagliptin compared to glimepiride over a median follow up of 6.3 years [50]. This section reviews data on the glucose-lowering medications by class. Several studies have examined the effect of SGLT2 inhibitors on renal function. Erratum in: Circulation. These results reinforce the CV benefits of SGLT2 inhibitors in practice-based settings. NSAID Prescribing Precautions | AAFP Similarly, the Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA) trial demonstrated no difference in CV outcomes and, importantly, no increased risk of HF hospitalizations in secondary analysis [78]. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. A A A The first scientific statement from the American Heart Association (AHA) on drugs that may cause or exacerbate heart failure (HF) reports that patients with HF on average take 6.8 prescription medications per day, which is approximately 10.1 doses per day. Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study. Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al. Non-dihydro Calcium Channel Blockers (CCB): Including (diltiazem and verapamil) have a negative inotropic effect, thus might increase adverse outcomes [1]. Research linking a daily glass of red wine to improve heart health remains inconclusive. The heart muscle is either too weak or not elastic enough. The condition is also known as cardiomegaly . Heart failure, sometimes called congestive heart failure, means your heart continues to pump blood and push oxygen throughout your body. Am Heart J. Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors. If HF develops, treat and consider dose reduction or discontinuation of pioglitazone. In the Efficacy of Pioglitazone on Macrovascular Outcomes in Patient with Type 2 Diabetes (PROACTIVE) trial, 5,238 patients with DM and macrovascular disease were randomized to receive pioglitazone or placebo and followed for a mean of 2 years [59]. Comparative safety of sulfonylurea and metformin monotherapy on the risk of heart failure: a cohort study. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Li L, Li S, Liu J, Deng K, Busse JW, Vandvik PO, et al. The SGLT1 is found in nephrons, heart, skeletal muscle and small intestine, where it is the primary mediator for glucose reabsorption. Heart failure is when the heart is not pumping blood as well as it needs to, leading to fluid build-up, swelling (known as edema), and shortness of breath. Medications with high sodium content: Excessive sodium . TCAuse with extreme caution in patients with a history of CVD or family history of sudden death, dysrhythmias, or conduction abnormalities. Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. The accuracy, completeness and validity of any statements made within this article are not guaranteed. The baseline prevalence of HF in these studies were relatively low, ranging from 8.6% in REWIND to 23.6% in SUSTAIN-6. FOIA Swelling in the legs, ankles and feet. Packer M. Do DPP-4 inhibitors cause heart failure events by promoting adrenergically mediated cardiotoxicity? Empagliflozin and the risk of heart failure hospitalization in routine clinical care. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Wheezing. These Common Medications Can Make Heart Failure Worse - GoodRx Learn about heart failure symptoms, causes, and treatments. Finally, in a large meta-analysis of 381,725 patients with acute and chronic HF over a median follow-up of 3 years, DM was associated with a higher risk of all-cause death (HR, 1.28; 95% CI, 1.21 to 1.35), CV death (HR, 1.34; 95% CI, 1.20 to 1.49), and hospitalization (HR, 1.35; 95% CI, 1.20 to 1.50) [23]. Summary of dipeptidyl peptidase-IV inhibitor cardiovascular outcome trials. 2 HF is a progressive disease that can result from any structural or functional changes of the heart, leading to the impairment of ventricular filling or . 10 Things to Avoid for a Healthier Heart [11] Wu CK, Lin JW, Wu LC, Chang CH. Metformin use was associated with a reduced adjusted risk of HF hospitalization (aHR, 0.57; 95% CI, 0.53 to 0.62) and all-cause mortality (aHR, 0.67; 95% CI, 0.60 to 0.75) [44]. Data from CV outcomes trials have underscored that HF is a critical outcome in patients with diabetes and suggest that glucose-lowering medications may influence the risk of HF development and progression. Pharmacologic Management of Gout in Patients with Cardiovascular Overall, SGLT2 inhibitors have demonstrated consistent reductions in CV mortality and HF hospitalizations making them the therapeutic agent of choice in the treatment of T2DM in patients with established HF or at high risk for developing HF. If you're worried about your heart, you'll want to keep these out of. There are currently four FDA-approved DPP-4 inhibitors available for the treatment of T2DMsaxagliptin, alogliptin, sitagliptin, and linagliptin. In particular, the consistent reductions in CV mortality and HF hospitalizations with SGLT2 inhibitors suggest that they should be considered in all patients with T2DM with HF or at high risk for developing HF. Ruminations of a Cardiology Fellow, Primordial Prevention of Cardiovascular Disease through Heart-Healthy Diet, E-cigarette use is a health concern, but long-term consequences remain unknown, PET or MRI, that is the question Part 2. Similarly, the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial, weekly exenatide did not reduce CV events or mortality compared to placebo [64]. The clinical use is further limited by the spectrum of side effects that include weight gain, decrease in hematocrit values, edema, heart failure, fractures, and worsening of diabetic macular edema. Is Having an Enlarged Heart Serious? Heart Failure - What Is Heart Failure? | NHLBI, NIH These findings raise the possibility that previously reported observational studies linking insulin use to HF may have confounded insulin use with other factors linked to poor prognosis (i.e., advanced age, difficult to control T2DM, chronic kidney disease [CKD]). 1 The lifetime risk of HF at 45 years of age is 30% for white men and 32% for white women. Finally, the Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) trial found no difference in major adverse CV events or HF hospitalizations in 6,033 patients randomized to either linagliptin (DPP-IV inhibitor) or glimepiride (sulfonylurea) [50]. In the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), 3,730 symptomatic HFrEF patients were assigned to received either empagliflozin or placebo, in addition to standard therapy. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. UK Prospective Diabetes Study (UKPDS) Group. In modern medicine, we tend to have a generally negative feeling about sodium, the element found in salt. AAA: anti-arrhythmic agents. PMID: 28467883. Sotagliflozin in patients with diabetes and recent worsening heart failure. PMID: 9141377. And after his dramatic resignation, Lord Goldsmith has spoken out . Kidney, Cardiac, and Safety Outcomes Associated With -Blockers in Patients With CKD: A Population-Based Cohort Study. Recent trial results indicating benefits of SGLT2 inhibitors, regardless of whether they have T2DM indicate an important role of these drugs in the management of patients with HFrEF. Iribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S, et al. Metformin in heart failure patients. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Metformin is generally safe to use in patients with HF and T2DM but should be discontinued in patients who present with acute decompensated HF or have estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2. Dapagliflozin in patients with heart failure and reduced ejection fraction. Nonsteroidal Anti-Inflammatory Drugs (NSAID) : Diclofenac , indomethacin , ketorolac ..etc AND COX-2 selective inhibitors (Celecoxib) : Introduction. The heart keeps pumping, but it's not pumping blood throughout the body as efficiently as it once did. Celecoxib is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [2]. Eplerenone in patients with systolic heart failure and mild symptoms. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.