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.



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