Reducing Patient Risk for ACS

New Orleans—Cardiovascular disease (CVD) is the most common cause of death in the United States. Acute coronary syndrome (ACS), a common complication of CVD, encompasses clinical disorders ranging from ST-elevation myocardial infarction (STEMI) to non−ST-elevation myocardial infarction (NSTEMI) and unstable angina.

James A. de Lamos, MD, FACC, and Jeffrey L. Anderson, MD, discussed the use of oral antiplatelet therapies and guideline recommendations for ACS during a symposium at the CRS meeting.

Antiplatelet Therapies
Antiplatelet therapies are routinely used in the treatment of ACS. Dr. de Lamos, professor of medicine, University of Texas Southwestern Medical Center, reviewed the similarities and differences in the pharmacologic profiles of these drugs.

Aspirin is a nonsteroidal anti-inflammatory agent that irreversibly inhibits platelet function. Dr. de Lamos highlighted a meta-analysis published in British Medical Journal in 2002 that reviewed antiplatelet therapies, including aspirin in high-risk patients with acute or previous vascular disease or some other predisposing condition. The researchers concluded that aspirin or other oral antiplatelet drugs are protective in most patients who are at increased risk of occlusive vascular events, including those with an acute myocardial infarction (MI) or ischemic stroke, unstable or stable angina, previous MI, stroke or cerebral ischemia, peripheral arterial disease, or atrial fibrillation. Furthermore, low-dose aspirin (75 mg-150 mg daily) is an effective antiplatelet regimen for long-term use, but in acute settings, an initial loading dose of at least 150 mg aspirin may be required.

Dr. de Lamos, who said that aspirin 81 mg is the preferred dose after the initial dose administered in the emergency department or catheterization laboratory, reviewed the American College of Cardiology (ACC)/American Heart Association (AHA) primary prevention guidelines for aspirin use (Table 1).

Clopidogrel, prasugrel, and ticagrelor are P2Y₁₂ inhibitors that can be used in patients unable to tolerate aspirin or can be used in combination with aspirin (Table 2). Dr. de Lamos highlighted the results of  clinical trials with these therapies. The primary end point for the trials was a composite of death from cardiovascular causes, nonfatal MI, or stroke. In order to further illustrate various ACS treatments, Dr. de Lamos reviewed 3 trials.

CURE Trial
In the CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events] trial, 12,562 NSTEMI patients were randomized to receive aspirin therapy in addition to either placebo or clopidogrel (300 mg loading dose, followed by 75 mg once daily) for 3 to 12 months after index. The findings, reported by Yusuf et al in New England Journal of Medicine in 2001, showed that clopidogrel provided a 20% relative risk reduction in the composite outcome of cardiovascular death, MI, or stroke. Overall, there were 719 (11.4%) first events in the placebo group and 582 (9.3%) in the clopidogrel group, according to Dr. de Lamos. An increase in the rate of major bleeding events was observed with the clopidogrel group versus the placebo group (3.7% vs 2.7%, respectively), but with a nonsignificant increase in episodes of life-threatening bleeding (2.2% vs 1.8%, respectively).

TRITON-TIMI 38 Trial
TRITON-TIMI [Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction] 38 trial compared prasugrel (60 mg loading dose, followed by 10 mg daily dose) and clopidogrel (300 mg loading dose, followed by 75 mg once daily) for 6 to 15 months in patients with moderate to high-risk ACS with scheduled percutaneous coronary intervention (PCI). The results were reported by Wiviott et al in New England Journal of Medicine in 2007.

The findings showed that composite primary end point occurred in 11.2% of clopidogrel-treated
patients and 9.3% of prasugrel-treated patients, mostly driven by a significant risk reduction for MI (from 9.2%-7.1%), said Dr. de Lamos. Major bleeding was observed in 2.4% of patients receiving prasugrel and 1.8% of patients receiving clopidogrel. The rate of life-threatening bleeding was greater in the prasugrel group than the clopidogrel group (1.4% vs 0.9%, respectively), including nonfatal bleeding (1.1% vs 0.9%, respectively) and fatal bleeding (0.4% vs 0.1%, respectively).

PLATO Trial
The final trial Dr. de Lamos reviewed was the PLATO [Platelet Inhibition and Patient Outcomes] trial, reported by Wallentin et al in New England Journal of Medicine in 2009. Patients with either moderate to high-risk non−ST-elevation ACS (planned for either conservative or invasive management) or STEMI planned for primary PCI were randomized to receive either clopidogrel (300 mg loading dose, 75 mg daily thereafter) or ticagrelor (180 mg loading dose, 90 mg twice daily thereafter). Treatment was continued for 12 months. The results demonstrated that the primary end point occurred in 9.8% of patients receiving ticagrelor compared to 11.7% of patients receiving clopidogrel. No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively).

He noted that ticagrelor carries a black box warning that maintenance doses of aspirin >100 mg reduce the effectiveness of the drug and should be avoided.

Guideline Recommendations
In addition to applying clinically proven treatment regimens, primary care providers (PCPs) should outline a plan of care for secondary prevention of CVD, which includes the management of cardiovascular risk factors with lifestyle changes and drug therapy as indicated. Dr. Anderson, professor of internal medicine, University of Utah School of Medicine, concluded the symposium with a discussion of prevention guidelines.

The 2013 ACC/AHA guideline for the management of STEMI outlines a post-hospitalization plan of care for this patient population (J Am Coll Cardiol. 2013;61(4):e-78-e140). Recommendations include:

     • A clear, detailed, and evidence-based plan of care that promotes medication adherence, timely
       follow-up with the healthcare team, appropriate dietary and physical activities, and compliance   
       with interventions for secondary prevention
     • Encouragement and advice to stop smoking and to avoid secondhand smoke      

The ACC/AHA recently released 4 guidelines that focused on the assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of cholesterol and body weight in adults. Dr. Anderson highlighted key recommendations from the Guideline on Lifestyle Management to Reduce Cardiovascular Risk (J Am Coll Cardiol. 2014;63(25 Pt B):2960-2984):
     • Clinicians should emphasize the intake of vegetables, fruits, and whole grains into patient diet
     • Clinicians should emphasize the inclusion of low-fat dairy, poultry, fish, legumes, nontropical
       vegetable oil, and nuts into patient diet
     • Clinicians should recommend limiting patient intake of sweets, sugar-sweetened beverages, and
       red meats
     • For low-density lipoprotein lowering, decrease percentage of calories from saturated and
       unsaturated fats
     • For blood pressure lowering, reduce sodium intake by ≥1000 mg/day and target sodium intake to
       ≤2400 mg/day
     • Patients should perform 40 minutes of moderate to vigorous physical activity 3 to 4 times a week

Since obesity is a part of the cardiometabolic syndrome spectrum, Dr. Anderson said that PCPs can refer to the Guideline for the Management of Overweight and Obesity in Adults (J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023). If a patient is overweight (body mass index [BMI] 25 kg/m²-29.9 kg/m²) or obese (BMI ≥30 kg/m2), Dr. Anderson said that clinicians should recommend that patients set a target goal of 5% to 10% weight loss over 6 months by restricting calorie intake and/or increasing physical activity. Clinicians should consider adding pharmacotherapy if BMI is ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities.

Finally, bariatric surgery may be an option if BMI is ≥40 kg/m² or ≥35 kg/m² with obesity-related comorbidities.

He concluded that an association between hospital guideline adherence and in-hospital mortality in
patients with ACS does improve outcomes in this patient population. A study by Petersen et al published in Journal of American Medical Association in 2006 conducted an observational analysis of hospital care in 350 academic and nonacademic US centers with 64,775 patients enrolled in the CRUSADE [Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines] trial. The primary outcome measure was use of 9 ACC/AHA class 1 guideline-recommended treatments and the correlation among hospitals’ use of individual care processes as well as overall composite adherence rates.

Overall, the results showed that the 9 ACC/AHA guideline-recommended treatments were adhered to in 74% of eligible instances.—Eileen Koutnik-Fotopoulos