Understanding the Latest Evidence on the Prevention and Treatment of Cardiovascular Disease

Author: Christine Zink, MD

Cardiovascular disease remains the leading cause of death globally. Over 18 million people died of cardiovascular disease in 2019 (1). Therefore, it’s imperative that all primary care clinicians understand cardiovascular pathophysiology, diagnostic criteria, treatment, and prevention. This article will focus on acute management and preventive strategies to help improve care for your patients.

  1. The Patient Has Chest Pain

When an adult patient presents to the clinic complaining of chest pain with associated symptoms, the clinician should assess the likelihood for underlying ischemic disease, initiate a diagnostic workup with an electrocardiogram, and begin treatment to relieve ischemic symptoms. Suppose there is a concern for unstable angina, acute non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI). In that case, the patient should be sent to an emergency department or higher care level for further management.

Based on the history alone, it is challenging to differentiate unstable angina from NSTEMI. Generally, the difference lies in whether a patient has positive cardiac biomarkers on diagnostic evaluation. However, these two entities are primarily managed in the same way. So, once a diagnosis of unstable angina or NSTEMI is made, what are the next management steps?

  1. Treatment of Patients with Unstable Angina and Acute Non-ST-Elevation Myocardial Infarction

Think Twice About Oxygen: Typically, patients who present with chest pain and associated symptoms have historically been provided supplemental oxygen. However, this treatment does not lead to any outcome benefits (2). The only patients who require supplemental oxygen are those with an oxygen saturation of less than 90% or those with respiratory distress from concomitant heart failure.

Good to Go With Nitroglycerin: Nitroglycerin is administered to patients with ischemic chest pain, particularly those with significant hypertension. There are very few studies that document the effectiveness of nitroglycerin on long-term outcomes. However, a few smaller studies show that, at the very least, nitroglycerin improves symptoms and reduces the frequency and duration of ischemic episodes (3). There is not a notable difference between intravenous, sublingual, or transdermal formulations. It must be used with caution in patients who are already hypotensive, have right ventricular infarction, or severe aortic stenosis. It also should not be used in patients who have recently taken a phosphodiesterase inhibitor for erectile dysfunction.

Stay Away From Morphine: Previously, it was commonplace for clinicians to use intravenous morphine for patients complaining of pain related to an acute coronary syndrome. However, a retrospective observational study shows that patients treated with morphine have a higher risk of death (4). No one is exactly sure why this might be the case, but experts think that morphine interferes with antiplatelet therapy.

Beta-blockers Are Often Added: Although there is a paucity of evidence showing a significant benefit to treatment with beta-blockers in patients with unstable angina and NSTEMI, there is no harm associated with its use (5). It has remained a mainstay of treatment because of its mortality benefits for patients with STEMI. Beta-blocker therapy should be initiated within 24 hours of symptom onset.

Definitely Include Antiplatelet Therapy: If there are no absolute contraindications, every patient with unstable angina or NSTEMI should be started on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor blocker (5). Antiplatelet treatment should begin as soon as a diagnosis is made. Few medications have proven to be as effective as aspirin for an acute coronary syndrome. The choice of a second antiplatelet agent is discussed further in the section on STEMI management.

Ignore Fibrinolysis: Fibrinolytic therapy is not beneficial in patients with NSTEMI.

Discuss Revascularization: There are conflicting opinions on which NSTEMI patients benefit from early revascularization therapy. The TIMI risk score and an assessment of cardiovascular stability help clinicians decide whether to institute a conservative approach, an invasive approach with angiography in 24–48 hours, or an immediate angiography approach. Generally, immediate angiography and revascularization are only indicated in patients with hemodynamic instability, severe left ventricular dysfunction or heart failure, refractory angina pain despite intensive medical therapy, mechanical complications such as acute mitral regurgitation, sustained ventricular tachycardia, or dynamic ST-T-wave changes on the electrocardiogram (6). Patients who do not fall into a high-risk category but still have a TIMI risk score greater than two are usually referred for angiography and revascularization in the next 24–48 hours. A 2006 meta-analysis concluded that this approach leads to better outcomes compared to conservative therapy (6).

However, what if the patient is having a STEMI. How should patients with an acute STEMI be treated differently than those with unstable angina or NSTEMI?

  1. Treatment of Patients with ST-Elevation Myocardial Infarction

The significant difference in managing patients with STEMI is that they benefit from acute fibrinolysis or percutaneous coronary intervention (PCI) and reperfusion as quickly as possible.

Use PCI ASAP: Multiple randomized trials show enhanced survival, a lower rate of recurrent myocardial infarction, and less risk of intracranial hemorrhage using PCI compared to fibrinolysis (7). PCI should be done as soon as possible, and the standard is within 90 minutes. This remains true even if interventional facilities are not available in the hospital, but the patient can be transported to a PCI-capable facility within 120 minutes.

Consider Fibrinolysis: If PCI cannot be accomplished in under 120 minutes, experts recommend that patients receive fibrinolysis before transport and intervention (8,9). The mortality benefit of fibrinolytic therapy decreases as time passes, particularly if given six hours after symptom onset. Furthermore, there is no benefit to giving a fibrinolysis 12 hours after symptom onset.

Add Anticoagulants: During a STEMI, antithrombotic therapy has many facets, including fibrinolysis, reperfusion, antiplatelet therapy, and anticoagulant therapy. This approach aims to prevent intraluminal clot extension and reformation when the clot has already undergone fibrinolysis by intrinsic mechanisms. Anticoagulants have a small proven benefit in decreasing mortality in patients with a STEMI whether they receive fibrinolytic therapy, percutaneous coronary intervention, or no reperfusion therapy. The medication choice can depend on several factors, including other antithrombotic therapy used and whether the patient is undergoing PCI. However, the evidence is best for low molecular weight heparin, such as enoxaparin (10). Research is still ongoing on other anticoagulants’ benefits, such as direct thrombin inhibitors and the factor Xa inhibitor, fondaparinux.

Definitely Include Antiplatelet Therapy: Patients with STEMI should undergo DAPT with aspirin and a second agent. This remedy prevents further ischemic events, and in patients who receive PCI will also prevent stent thrombosis. In clinical practice, the medication choice is decided in consultation with a cardiologist since antiplatelet therapy can complicate coronary artery bypass grafting. Clopidogrel has classically been the second agent of choice and is still recommended for patients receiving fibrinolysis, too. However, studies show that PCI patients show improved outcomes with prasugrel or ticagrelor without increased bleeding risks (11,12).

Statins Should Be Included, Too: Statin therapy is recommended as soon as possible for all patients admitted to the hospital with acute coronary syndrome irrespective of the patient’s baseline low-density lipoprotein cholesterol (LDL-C) level. The choice of medication largely depends on the patient’s initial LDL-C level (13). In patients who have not taken a statin before, the first-line medication options are usually atorvastatin and rosuvastatin. In patients already taking lipid-lowering therapy, then ezetimibe is added.

  1. Prevention of Ischemic Cardiovascular Disease

Patients with established cardiovascular disease are at a higher risk for myocardial infarction, stroke, and death. The primary care clinician needs to encourage lifestyle and medical changes to reduce cardiovascular events’ risk (14). Lifestyle modifications that show clear benefits include increased physical activity, weight reduction, and smoking cessation. Dietary modifications should focus on a higher intake of vegetables, fruits, nuts, whole grains, lean animal proteins, and fish. People should minimize their intake of trans fats, red meat, refined carbohydrates, and sweetened beverages.

It is also important to control chronic medical conditions such as dyslipidemia, hypertension, and diabetes mellitus. The goal is to achieve an LDL-C level below 50 mg/dL. The goal level for blood pressure is 120/80 mmHg. The target for hemoglobin A1c levels should be individualized, but a level less than 7% is an excellent place to start (15).

Other Adjunctive Therapies:

  • Patients with established cardiovascular disease should take daily aspirin. Clopidogrel is a reasonable alternative for patients who cannot take aspirin.
  • Patients who have had PCI with stenting also need to remain on DAPT, and ticagrelor is recommended based on the THEMIS study (16). However, recent studies suggest that patients 70 years and older benefit from clopidogrel instead. They have fewer episodes of bleeding with an equivalent number of ischemic events (17).
  • Patients who have had a myocardial infarction or those with underlying heart failure have decreased mortality if maintained on an oral beta-blocker (18). However, new evidence suggests that this long-term benefit decreases after approximately three years (19).
  • Finally, new evidence suggests that colchicine’s anti-inflammatory properties reduce the risk of cardiovascular events in patients with chronic coronary disease (20).

Adjunctive treatments that are still being evaluated or have not proven useful include antioxidant vitamins, folic acid, postmenopausal hormone therapy, chelation therapy, cholesteryl-ester transfer protein inhibitors, and methotrexate.

The management of cardiovascular disease is one of the most critical endeavors bestowed upon primary care clinicians, and the aspects of care are multifaceted and complex. Earn credits and learn more about how you can improve care for patients through Pri-Med’s free online Cardiology CME/CE.

 

Resources

1. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study. J Am Coll Cardiol 2020;76:2982-3021.

2. Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, Arefalk G, Frick M, Alfredsson J, Nilsson L, Ravn-Fischer A, Omerovic E, Kellerth T, Sparv D, Ekelund U, Linder R, Ekström M, Lauermann J, Haaga U, Pernow J, Östlund O, Herlitz J, Svensson L; DETO2X–SWEDEHEART Investigators. Oxygen Therapy in Suspected Acute Myocardial Infarction. N Engl J Med. 2017 Sep 28;377(13):1240-1249.

3. Karlberg KE, Saldeen T, Wallin R, Henriksson P, Nyquist O, Sylvén C. Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double-blind placebo-controlled study. J Intern Med. 1998 Jan;243(1):25-31.

4. Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, Peacock WF, Pollack CV Jr, Gibler WB, Peterson ED; CRUSADE Investigators. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J. 2005 Jun;149(6):1043-9.

5. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ; ACC/AHA Task Force Members; Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 23;130(25):2354-94.

6. Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol. 2006 Oct 3;48(7):1319-25. doi: 10.1016/j.jacc.2006.06.050. Epub 2006 Sep 12. PMID: 17010789.

7. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003 Jan 4;361(9351):13-20.

8. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet. 1994 Feb 5;343(8893):311-22. Erratum in: Lancet 1994 Mar 19;343(8899):742. PMID: 7905143.

9. Gersh BJ, Stone GW, White HD, Holmes DR Jr. Pharmacological facilitation of primary percutaneous coronary intervention for acute myocardial infarction: is the slope of the curve the shape of the future? JAMA. 2005 Feb 23;293(8):979-86.

10. Eikelboom JW, Quinlan DJ, Mehta SR, Turpie AG, Menown IB, Yusuf S. Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the randomized trials. Circulation. 2005 Dec 20;112(25):3855-67.

11. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57.

12. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15.

13. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504.

14. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 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. Circulation. 2019 Sep 10;140(11):e596-e646.

15. Hennekens CH, Lopez-Sendon J. Overview of the prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk. Post TW, ed. UpToDate. UpToDate Inc. Accessed February 10, 2021. https://www.uptodate.com/contents/overview-of-the-prevention-of-cardiovascular-disease-events-in-those-with-established-disease-secondary-prevention-or-at-very-high-risk.

16. Steg PG, Bhatt DL, Simon T, Fox K, Mehta SR, Harrington RA, Held C, Andersson M, Himmelmann A, Ridderstråle W, Leonsson-Zachrisson M, Liu Y, Opolski G, Zateyshchikov D, Ge J, Nicolau JC, Corbalán R, Cornel JH, Widimský P, Leiter LA; THEMIS Steering Committee and Investigators. Ticagrelor in Patients with Stable Coronary Disease and Diabetes. N Engl J Med. 2019 Oct 3;381(14):1309-1320.

17. Gimbel M, Qaderdan K, Willemsen L, Hermanides R, Bergmeijer T, de Vrey E, Heestermans T, Tjon Joe Gin M, Waalewijn R, Hofma S, den Hartog F, Jukema W, von Birgelen C, Voskuil M, Kelder J, Deneer V, Ten Berg J. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020 Apr 25;395(10233):1374-1381.

18. AHA; ACC; National Heart, Lung, and Blood Institute, Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pearson T, Pfeffer MA, Taubert KA. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006 May 16;47(10):2130-9.

19. Kim J, Kang D, Park H, Kang M, Park TK, Lee JM, Yang JH, Song YB, Choi JH, Choi SH, Gwon HC, Guallar E, Cho J, Hahn JY. Long-term β-blocker therapy and clinical outcomes after acute myocardial infarction in patients without heart failure: nationwide cohort study. Eur Heart J. 2020 Oct 1;41(37):3521-3529.

20. Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847.