Congestive heart failure drugs to avoid

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorraine Co, DMD, MD[2]

Overview

Drugs like nonsteroidal anti-inflammatory drugs, antiarrhythmic agents, and calcium channel blockers should be avoided in patients with congestive heart failure as they are known to have negative or deleterious effects on cardiac contractility, the neurohormonal system, or may cause sodium retention.

Drugs to Be Avoided in Congestive Heart Failure

Calcium Channel Blockers

There is no direct role of calcium channel blockers in the management of CHF. Given that some agents (diltiazem and verapamil) have a negative inotropic effect, it has been hypothesized that calcium channel blockers might increase adverse outcomes among patients with CHF due to systolic dysfunction. [1]. Vasoselective calcium channel blockers such as amlodipine and felodipine have not been linked to adverse outcomes among patients with congestive heart failure, but there is likewise no evidence of efficacy for these drugs in the management of CHF.[2] If a congestive heart failure patient has either angina or hypertension as a concomitant disease, amlodipine and felodipine appear to be safe for the treatment of these patients.

Antiarrhythmic Agents

Negative inotropic effect exerted by most antiarrhythmic drugs can precipitate CHF in patients with reduced LV function, and [antiarrhythmic]] agents can also paradoxically be pro-arrhythmic. The reduction in LV function can also reduce the elimination of these drugs leading to further drug toxicity. Other antiarrhythmic drugs can induce some proarrhythmic effect, especially class 1 agents and class 3 agents Ibutilide and sotalol (which has a negative inotropic effect);[3] the same class 3 agents in addition to dofetilide can induce torsades to pointes. Amiodarone is considered the safest of the antiarrhythmic drugs because of its minimal proarrhythmic effect and is generally the preferred drug for treating arrhythmias in CHF patients.Dronedarone should be avoided in patients who were hospitalized with CHF (this is a boxed warning). Disopyramide is contraindicated in patients with heart failure.

Nonsteroidal Anti-Inflammatory Drugs (NSAID)

The administration of non-selective NSAIDs in CHF patients has been linked to:

COX-2 selective inhibitors

Observational data suggest that these agents may be linked with an increase in congestive heart failure exacerbations as well as an increased mortality.[4]

Aspirin

Aspirin is often prescribed as primary prevention in patients with risk factors for cardiovascular disease or as secondary prevention in patients with established cardiovascular disease. However, among patients with congestive heart failure, the risks and benefits of aspirin are not as well established. Concern has arisen regarding the potential interaction between aspirin with ACEIs and beta blockers. At this time the American College of Chest Physicians guidelines indicate that it is reasonable to withhold aspirin among patients who have non-ischemic heart failure, while it may be reasonable to continue aspirin among those patients who have ischemic heart failure.

Although there is some data to suggest that aspirin may attenuate some of the hemodynamic benefits of ACE inhibitors, there is no data indicating that the beneficial clinical outcomes associated with ACE inhibitors is reduced.
There is likewise some data to suggest that aspirin may attenuate the benefit of beta blockers on the left ventricular ejection fraction among patients with congestive heart failure.

Oral Hypoglycemic Agents

Metformin is associated with lactic acidosis, which can be fatal in patients with CHF.[5]
Administration of thiazolidinediones is associated with fluid retention which may in turn cause volume overload and worsening of patients with CHF.[6]

Antidepressants

Depression among patients with congestive heart failure is associated with poorer clinical outcomes including higher mortality.[7] Questions have been raised as to whether it isthe depression itself that directly harms congestive heart failure patients or whether the harm is mediated by treatment with drugs such as tricyclic antidepressants. It appears that it is the depression itself and not the drugs used to treat depression that is independently associated with worse clinical outcomes. There is no difference in the risk of adverse outcomes among heart failure patients treated with either tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs).

Phosphodiesterase inhibitors PDE

Chemotherapy

Cardiotoxic chemotherapeutic agents as Cyclophosphamide, Trastuzumab, Bevacizumab and Anthracyclines, should be avoided in CHF patients [12]

Tumor Necrosis Factor alpha inhibitors (TNF-alpha)

New onset or worsening of pre-existing heart failure have been linked to TNF-alpha inhibitors.[13] Infliximab has been specifically contraindicated in doses over 5mg/kg in patients with heart failure.

Antihistamines

Some second generation antihistamines as terfenadine and astemizole have been reported to cause long QT syndrome and should not be used in CHF patients.[14]

Serum Potassium

Serum potassium should be closely monitored in CHF patients, in order of preventing either hypokalemia or hyperkalemia, which could greatly affect cardiac excitability and conduction, leading to sudden cardiac death.[15] Serum potassium should be maintained between 4.0 to 5.0 mEq per liter range, because low potassium level may affect digitalis and antiarrhythmic drugs treatment, while high potassium level can prevent the use of treatments known to prolong life.[15]

Supervision of CHF patients with close monitoring of treatment and diet is a very important aspect of the follow-up process in those individuals. Body weight and medications should be closely monitored, because any minor change in those parameters can have a significant effect over symptoms and hospitalization of patients with CHF.[16] Patient education is a crucial aspect of the management of CHF, patient and family surveillance over any new change of symptoms or body weight is important in allowing early detection of those changes and implementing new treatment strategies to reduce further complications.[17]

Theophyline

Decompensation of congestive heart failure can be associated with theophylline toxicity, even at normal theophylline levels. If theophylline must be administered, the dosing should be reduced in the heart failure patient.

2022 AHA/ACC/ HFSA Heart Failure Guideline (DO NOT EDIT) [18]

Drugs of Unproven Value or That May Worsen HF

Class III (No Benefit)
"1. In patients with HFrEF, dihydropiridine calcium channel-blocking drugs are not recommended treatment for HF.[19][20] (Level of Evidence: A) "
"2. In patients with HFrEF, vitamins, nutritional supplements, and hormonal therapy are not recommended other than to correct specific deficiencies. [21][22][23][24][25][26][27] (Level of Evidence: B-R) "
Class III (Harm)
"3. In patients with HFrEF, non-dihydropiridine calcium channel-blocking drugs are not recommended. [28][29][30][31] (Level of Evidence: A) "
"4.In patients with HFrEF, class IC antiarrhythmic medications and dronedarone may increase the risk of mortality. [32][33][34] (Level of Evidence: A) "
"5.In patients with HFrEF, thiazolidinediones increase the risk of worsening HF symptoms and hospitalizations. [35][36][37][38][39](Level of Evidence: A) "
"6.In patients with type 2 diabetes and high cardiovascular risk, the dipeptidyl peptidase-4 (DPP-4) inhibitors saxagliptin and alogliptin increase the risk of HF hospitalization and should be avoided in patients with HF. [40][41][42](Level of Evidence: B-R) "
"7.In patients with HFrEF, NSAIDs worsen HF symptoms and should be avoided or withdrawn whenever possible. [43][44][45][46] (Level of Evidence: B-NR) "

References

  1. ↑ Packer M, Kessler PD, Lee WH (1987). "Calcium-channel blockade in the management of severe chronic congestive heart failure: a bridge too far". Circulation. 75 (6 Pt 2): V56–64. PMID 3552317. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  2. ↑ Reed SD, Friedman JY, Velazquez EJ, Gnanasakthy A, Califf RM, Schulman KA (2004). "Multinational economic evaluation of valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT)". American Heart Journal. 148 (1): 122–8. doi:10.1016/j.ahj.2003.12.040. PMID 15215801. Retrieved 2011-04-07. Unknown parameter |month= ignored (help)
  3. ↑ Torp-Pedersen C, Møller M, Bloch-Thomsen PE, Køber L, Sandøe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ (1999). "Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group". The New England Journal of Medicine. 341 (12): 857–65. doi:10.1056/NEJM199909163411201. PMID 10486417. Retrieved 2011-04-07. Unknown parameter |month= ignored (help)
  4. ↑ Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A (1998). "NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics". Archives of Internal Medicine. 158 (10): 1108–12. PMID 9605782. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  5. ↑ Gan SC, Barr J, Arieff AI, Pearl RG (1992). "Biguanide-associated [[lactic acidosis]]. [[Case report]] and review of the literature". Archives of Internal Medicine. 152 (11): 2333–6. PMID 1444694. Retrieved 2011-04-08. Unknown parameter |month= ignored (help); URL–wikilink conflict (help)
  6. ↑ Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM (2005). "Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study". Circulation. 111 (5): 583–90. doi:10.1161/01.CIR.0000154542.13412.B1. PMID 15699279. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  7. ↑ Swenson JR, Doucette S, Fergusson D (2006). "Adverse cardiovascular events in antidepressant trials involving high-risk patients: a systematic review of randomized trials". Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 51 (14): 923–9. PMID 17249635. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  8. ↑ Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2006). "ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation". Circulation. 113 (11): e463–654. doi:10.1161/CIRCULATIONAHA.106.174526. PMID 16549646. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  9. ↑ Storen EC, Tefferi A (2001). "Long-term use of anagrelide in young patients with essential thrombocythemia". Blood. 97 (4): 863–6. PMID 11159509. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  10. ↑ "Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group". The American Journal of Medicine. 92 (1): 69–76. 1992. PMID 1731512. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  11. ↑ Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ (2007). "Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension". Circulation. 116 (14): 1555–62. doi:10.1161/CIRCULATIONAHA.107.716373. PMID 17785618. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  12. ↑ Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001). "Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2". The New England Journal of Medicine. 344 (11): 783–92. doi:10.1056/NEJM200103153441101. PMID 11248153. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  13. ↑ Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT (2003). "Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial". Circulation. 107 (25): 3133–40. doi:10.1161/01.CIR.0000077913.60364.D2. PMID 12796126. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  14. ↑ Yap YG, Camm AJ (2003). "Drug induced QT prolongation and torsades de pointes". Heart (British Cardiac Society). 89 (11): 1363–72. PMC 1767957. PMID 14594906. Retrieved 2011-04-08. Unknown parameter |month= ignored (help)
  15. ↑ 15.0 15.1 Packer M, Gottlieb SS, Kessler PD (1986). "Hormone-electrolyte interactions in the pathogenesis of lethal cardiac arrhythmias in patients with congestive heart failure. Basis of a new physiologic approach to control of arrhythmia". The American Journal of Medicine. 80 (4A): 23–9. PMID 2871753. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  16. ↑ Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM (1995). "A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure". The New England Journal of Medicine. 333 (18): 1190–5. doi:10.1056/NEJM199511023331806. PMID 7565975. Retrieved 2011-04-10. Unknown parameter |month= ignored (help)
  17. ↑ Philbin EF (1999). "Comprehensive multidisciplinary programs for the management of patients with congestive heart failure". Journal of General Internal Medicine. 14 (2): 130–5. PMID 10051785. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  18. ↑ Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e876–e894. doi:10.1161/CIR.0000000000001062. PMID 35363500 Check |pmid= value (help).
  19. ↑ Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN; et al. (1996). "Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group". N Engl J Med. 335 (15): 1107–14. doi:10.1056/NEJM199610103351504. PMID 8813041.
  20. ↑ Packer M, Carson P, Elkayam U, Konstam MA, Moe G, O'Connor C; et al. (2013). "Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2)". JACC Heart Fail. 1 (4): 308–314. doi:10.1016/j.jchf.2013.04.004. PMID 24621933.
  21. ↑ Djoussé L, Cook NR, Kim E, Bodar V, Walter J, Bubes V; et al. (2020). "Supplementation With Vitamin D and Omega-3 Fatty Acids and Incidence of Heart Failure Hospitalization: VITAL-Heart Failure". Circulation. 141 (9): 784–786. doi:10.1161/CIRCULATIONAHA.119.044645. PMC 7054158 Check |pmc= value (help). PMID 31709816.
  22. ↑ Wang T, Liu Z, Fu J, Min Z (2019). "Meta-analysis of vitamin D supplementation in the treatment of chronic heart failure". Scand Cardiovasc J. 53 (3): 110–116. doi:10.1080/14017431.2019.1612084. PMID 31032644.
  23. ↑ Zittermann A, Ernst JB, Prokop S, Fuchs U, Gruszka A, Dreier J; et al. (2019). "Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial". Int J Cardiol. 280: 117–123. doi:10.1016/j.ijcard.2019.01.027. PMID 30654912.
  24. ↑ Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM; et al. (2005). "Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial". JAMA. 293 (11): 1338–47. doi:10.1001/jama.293.11.1338. PMID 15769967.
  25. ↑ Marchioli R, Levantesi G, Macchia A, Marfisi RM, Nicolosi GL, Tavazzi L; et al. (2006). "Vitamin E increases the risk of developing heart failure after myocardial infarction: Results from the GISSI-Prevenzione trial". J Cardiovasc Med (Hagerstown). 7 (5): 347–50. doi:10.2459/01.JCM.0000223257.09062.17. PMID 16645413.
  26. ↑ Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D; et al. (2014). "The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial". JACC Heart Fail. 2 (6): 641–9. doi:10.1016/j.jchf.2014.06.008. PMID 25282031.
  27. ↑ Madmani ME, Yusuf Solaiman A, Tamr Agha K, Madmani Y, Shahrour Y, Essali A; et al. (2014). "Coenzyme Q10 for heart failure". Cochrane Database Syst Rev (6): CD008684. doi:10.1002/14651858.CD008684.pub2. PMID 24049047.
  28. ↑ "Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II)". Am J Cardiol. 66 (10): 779–85. 1990. doi:10.1016/0002-9149(90)90351-z. PMID 2220572.
  29. ↑ Multicenter Diltiazem Postinfarction Trial Research Group (1988). "The effect of diltiazem on mortality and reinfarction after myocardial infarction". N Engl J Med. 319 (7): 385–92. doi:10.1056/NEJM198808183190701. PMID 2899840.
  30. ↑ Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S (1991). "Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group". Circulation. 83 (1): 52–60. doi:10.1161/01.cir.83.1.52. PMID 1984898.
  31. ↑ Figulla HR, Gietzen F, Zeymer U, Raiber M, Hegselmann J, Soballa R; et al. (1996). "Diltiazem improves cardiac function and exercise capacity in patients with idiopathic dilated cardiomyopathy. Results of the Diltiazem in Dilated Cardiomyopathy Trial". Circulation. 94 (3): 346–52. doi:10.1161/01.cir.94.3.346. PMID 8759075.
  32. ↑ Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH; et al. (1991). "Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial". N Engl J Med. 324 (12): 781–8. doi:10.1056/NEJM199103213241201. PMID 1900101.
  33. ↑ Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF; et al. (1996). "Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol". Lancet. 348 (9019): 7–12. doi:10.1016/s0140-6736(96)02149-6. PMID 8691967.
  34. ↑ Køber L, Torp-Pedersen C, McMurray JJ, Gøtzsche O, Lévy S, Crijns H; et al. (2008). "Increased mortality after dronedarone therapy for severe heart failure". N Engl J Med. 358 (25): 2678–87. doi:10.1056/NEJMoa0800456. PMID 18565860.
  35. ↑ Lipscombe LL, Gomes T, Lévesque LE, Hux JE, Juurlink DN, Alter DA (2007). "Thiazolidinediones and cardiovascular outcomes in older patients with diabetes". JAMA. 298 (22): 2634–43. doi:10.1001/jama.298.22.2634. PMID 18073359. Review in: ACP J Club. 2008 Jun 17;148(4):13
  36. ↑ Lago RM, Singh PP, Nesto RW (2007). "Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials". Lancet. 370 (9593): 1129–36. doi:10.1016/S0140-6736(07)61514-1. PMID 17905165. Review in: ACP J Club. 2008 Mar-Apr;148(2):39
  37. ↑ Dargie HJ, Hildebrandt PR, Riegger GA, McMurray JJ, McMorn SO, Roberts JN; et al. (2007). "A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure". J Am Coll Cardiol. 49 (16): 1696–704. doi:10.1016/j.jacc.2006.10.077. PMID 17448371.
  38. ↑ Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M; et al. (2009). "Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial". Lancet. 373 (9681): 2125–35. doi:10.1016/S0140-6736(09)60953-3. PMID 19501900. Review in: Ann Intern Med. 2009 Oct 20;151(8):JC4-8 Review in: Evid Based Med. 2009 Dec;14(6):168
  39. ↑ Giles TD, Miller AB, Elkayam U, Bhattacharya M, Perez A (2008). "Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction". J Card Fail. 14 (6): 445–52. doi:10.1016/j.cardfail.2008.02.007. PMID 18672190.
  40. ↑ Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P; et al. (2014). "Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial". Circulation. 130 (18): 1579–88. doi:10.1161/CIRCULATIONAHA.114.010389. PMID 25189213. Review in: Ann Intern Med. 2015 Apr 21;162(8):JC11
  41. ↑ Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez AT; et al. (2015). "Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial". Lancet. 385 (9982): 2067–76. doi:10.1016/S0140-6736(14)62225-X. PMID 25765696.
  42. ↑ Verma S, Goldenberg RM, Bhatt DL, Farkouh ME, Quan A, Teoh H; et al. (2017). "Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis". CMAJ Open. 5 (1): E152–E177. doi:10.9778/cmajo.20160058. PMC 5403656. PMID 28459046.
  43. ↑ Mamdani M, Juurlink DN, Lee DS, Rochon PA, Kopp A, Naglie G; et al. (2004). "Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study". Lancet. 363 (9423): 1751–6. doi:10.1016/S0140-6736(04)16299-5. PMID 15172772.
  44. ↑ Hudson M, Richard H, Pilote L (2005). "Differences in outcomes of patients with congestive heart failure prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs: population based study". BMJ. 330 (7504): 1370. doi:10.1136/bmj.330.7504.1370. PMC 558290. PMID 15947399.
  45. ↑ Gislason GH, Rasmussen JN, Abildstrom SZ, Schramm TK, Hansen ML, Fosbøl EL; et al. (2009). "Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure". Arch Intern Med. 169 (2): 141–9. doi:10.1001/archinternmed.2008.525. PMID 19171810. Review in: Ann Intern Med. 2009 Jun 16;150(12):JC6-12
  46. ↑ Feenstra J, Heerdink ER, Grobbee DE, Stricker BH (2002). "Association of nonsteroidal anti-inflammatory drugs with first occurrence of heart failure and with relapsing heart failure: the Rotterdam Study". Arch Intern Med. 162 (3): 265–70. doi:10.1001/archinte.162.3.265. PMID 11822918.

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