Question 1

Which of the following secondary prevention therapies are recommended for patients who survive the acute phase of STEMI?

     (A)    ACE inhibitors

      (B)     Anti-platelet therapy 

      (C)     Beta-blockers

      (D)    Lipid management (statins, etc.)  

      (E)     Smoking cessation, weight management, and

        blood pressure control

      (F)     B, C, and D

      (G)     All of the above      

 Explanation:

Secondary prevention therapies, unless contraindicated, are an essential part of the management of all patients with STEMI. The 2004 ACC/AHA guidelines recommend (Class I) that a daily dose of aspirin 75 to 162 mg orally should be given indefinitely to patients recovering from STEMI (substitute clopidogrel or ticlopidine if ASA allergy).[1] In addition, an ACEI should be prescribed at discharge for all patients without contraindications after STEMI (Class I).

Unless there are contraindications, the 2004 ACC/AHA guidelines also recommend that all patients after STEMI should receive prophylactic beta-blocker therapy and continue it indefinitely. (Class I for all except those at low risk; Class IIa for low risk).[1] Lipid management is recommended (Class I) with the goal of achieving target LDL-C level substantially less than 100 mg/dL. If LDL-C is not less than 100 mg/dl, patients should be prescribed drug therapy on hospital discharge, with preference given to statins.

According to the guidelines, patients recovering from STEMI who have a history of cigarette smoking should be strongly encouraged to stop smoking and to avoid secondhand smoke (Class I).[1] Counseling should be provided to the patient and family, along with pharmacological therapy and formal smoking-cessation programs as appropriate. Weight management and BP control should be instituted. Blood pressure should be treated with drug therapy to a target level of less than 140/90 mm Hg and to less than 130/80 mm Hg for patients with diabetes or chronic kidney disease (Class I). Lifestyle modification (weight control, dietary changes, physical activity, and sodium restriction) should be initiated in all patients with blood pressure greater than or equal to 120/80 mm Hg (Class I). Before hospital discharge, all STEMI patients should be educated about and actively involved in planning for adherence to the lifestyle changes and drug therapies that are important for the secondary prevention of cardiovascular disease.

Question 2

Which of the following beta-blockers have demonstrated a survival benefit in post-MI patients?

     (A)    Metoprolol 

      (B)     Atenolol 

      (C)     Carvedilol 

      (D)    Propranolol  

      (E)     Timolol  

      (F)     All of the above  

 Explanation:

Several beta-blockers have been studied to determine their short-term and long-term impact on survival and reinfarction. The beta-blockers that have clearly demonstrated an increase in survival and reduction in nonfatal reinfarction include the following: metoprolol[2,3]; atenolol[4]; carvedilol in patients with LV dysfunction[5]; propranolol[6,7]; and timolol.[8,9]

In addition, several metanalyses have combined all randomized trials of beta-blockers and analyzed the benefit separately in short- and long-term trials.[10-12]

Of the beta-blockers for which more than one clinical trial was available for analysis, Freemantle found the following beta-blockers achieved a statistically significant reduction in the odds of death: propranolol (0.71; 95%CI, 0.59 to 0.85), timolol (0.59; 95%CI, 0.46 to 0.77), and metoprolol (0.80; 95%CI, 0.66 to 0.96).[12] In a 1985 meta-analysis by Yusuf, ancillary properties of the beta-blockers such as sympathomimetic activity (ISA) and cardio- selectivity were evaluated for the impact on long-term survival. Beta-blockers with and without cardio-selectivity demonstrated statistically significant decreases in death, but beta-blockers with ISA did not. The pooled odds ratio for beta-blockers with ISA was 0.90 (95% CI, 0.77 to 1.05). [10]

In a subset of patients with AMI complicated by left-ventricular systolic dysfunction, the CAPRICORN trial demonstrated that carvedilol was associated with a significant survival benefit in patients treated long term.[5] There was a 23% relative reduction in all-cause mortality with carvedilol compared to placebo (Hazard Ratio, 0.77; 95%CI, 0.60 to 0.98; P=.03).

Question 3

When should patients with STEMI receive beta-blocker therapy?

     (A)    Only in the hospital 

      (B)     In the hospital and continued indefinitely  

      (C)     For only 10 to 14 days after the event  

      (D)    Only after hospital discharge  

      (E)     In the hospital and up to 3 days after

    discharge  

Explanation:

The benefits of beta-blocker therapy post-MI have been demonstrated both when initiated early and when initiated later in the clinical course.[1,10-12] The benefits pertain to patients with or without reperfusion therapy (thrombolytics or primary PCI).

Treatment should begin within a few days of the event, if not initiated acutely, and continue indefinitely.[1]

A meta-analysis of 31 trials evaluating long-term treatment (6 to 48 months), found the Odds Ratio (OR) of death was 0.77 (95%CI, 0.69 to 0.85).[12] Freemantle’s statistical model suggested an annual reduction of 1.2 deaths in 100 patients treated with beta-blockers after MI. The number needed to treat for 2 years to avoid a death was 42, which compares favorably with other treatments for patients with acute or past MI. There was also an annual reduction in reinfarction of 0.9 events in every 100.

Question4

Which of the following statements about post-STEMI beta-blocker therapy in the setting of thrombolysis is/are true?

     (A)    Use is contraindicated

      (B)     Benefit is reduced  

      (C)     Recommended in 2004 ACC/AHA guidelines

      (D)    Not required if reperfusion is successful  

      (E)     B and D    

Explanation:

.Most evidence for the survival benefit of beta-blockers post-MI was developed before the thrombolytic era so some physicians have questioned whether beta-blockers are still beneficial with current reperfusion therapies.[2-4,6,8,9,10,12] However, the benefits of beta-blocker therapy for secondary prevention have been demonstrated with or without reperfusion. In a recent randomized trial of carvedilol in post-MI patients with reduced ejection fraction, nearly half of the patients receive

d reperfusion therapy, and still there was a significant survival benefit from the beta-blocker.[5] Indeed, the 2004 ACC/AHA guidelines for management of patients with STEMI indicate that oral beta-blocker therapy should be administered promptly to those patients without a contraindication, regardless of concomitant fibrinolytic therapy or performance of primary PCI.[1]

Question 5

Which of the following comorbidities is/are associated with a lower rate of beta-blocker use as secondary prevention of MI?

     (A)    Heart failure

      (B)     Peripheral vascular disease

      (C)     Diabetes

      (D)    COPD

      (E)     A and D 

      (F)     All of the above         

Explanation:

Provider misconceptions about the contraindications of beta-blockers potentially contribute to lower usage of these agents in secondary prevention of myocardial infarction. A systematic literature review indicated a lower rate of beta-blocker treatment in secondary prevention of myocardial infarction in patients with diabetes, heart failure, COPD, asthma, and peripheral vascular disease.[20]

However, there is increasing evidence supporting the judicious use of beta-blockers post-MI in patients with many comorbid conditions that clinicians once considered as contraindications to beta-blocker therapy.[21] In recent years, a series of randomized, controlled clinical studies have demonstrated significant benefits of beta-blocker therapy on mortality and morbidity in patients with post-MI LVD and heart failure.[5,22-25] In fact, patients at greatest risk following their AMI, those with decreased LVEF, derive greater benefit from beta-blockers than patients with preserved LV function.

Beta-blocker therapy after AMI has shown survival benefits in patients with mild COPD.[26] According to the 2004 ACC/AHA guidelines, although relative contraindications may once have been thought to preclude the use of beta-blockers in some STEMI patients, evidence now suggests that the benefits of beta-blockers in reducing reinfarctions and mortality may actually outweigh the risks, even in patients with insulin-dependent diabetes mellitus, COPD, severe peripheral vascular disease, and moderate LV failure. However, the use of beta-blockers in patients with these co-morbid conditions should be monitored.[27]

Question6

Which of the following adverse events have been associated with beta-blocker therapy?

     (A)    Fatigue

      (B)     Depression  

      (C)     Sexual dysfunction  

      (D)    A and C  

      (E)     All of the above  

Explanation:

Although fatigue, depression, and sexual dysfunction have all been reported with beta-blocker use, the conventional wisdom that beta-blocker therapy is associated with substantial risks of these side effects is not supported by data from clinical trials.[16] A recent quantitative review of randomized trials that tested beta-blockers in patients with MI, heart failure, and hypertension (n ≈35000) found that beta-blockers were not associated with a statistically significant absolute annual increase in risk of reported depressive symptoms (6 per 1000 patients; 95% CI, -7 to 19). However, beta-blockers were associated with a small, statistically significant annual increase in risk of reported fatigue (18 per 1000 patients; 95% CI, 5-30). This would be equivalent to one additional report of fatigue for every 57 patients treated per year with beta-blockers. Most of the risk was associated with early-generation beta-blockers such as propranolol and timolol (P=0.04 vs late-generation beta-blockers such as metoprolol and atenolol). Also, a small, statistically significant annual increase in risk of reported sexual dysfunction was observed (5 per 1000 patients; 95% CI, 2-8); this would be equivalent to one additional report for every 199 patients treated per year.[16]

In a different study of adverse effects of beta-blockers in patients with heart failure, there was no significant absolute risk of fatigue (estimate 3 per 1000; 95% CI -2 to 9). In these patients with heart failure, however, beta-blocker therapy was associated with statistically significant absolute annual increases in risks of hypotension (11 per 1000; 95% CI 0-22), dizziness (57 per 1000; 95% CI, 11-104), and Brady cardia (38 per 1000; 95% CI 21-54). This was counterbalanced by reductions in mortality (34 per 1000; 95% CI 22-58), HF hospitalizations (40 per 1000; 95% CI 22-58), and reduction in worsening HF (52 per 1000; 95% CI, 10-94). [28]

Therefore, the development of any of these symptoms following AMI on beta-blocker therapy should not immediately be blamed on the beta-blocker. Careful review of the patient،¦s medical condition and other medications is warranted before changes in beta-blocker therapy are considered.

Question 7

Which of the following are absolute contraindications to beta-blocker therapy in STEMI patients?

     (A)    High-grade heart block  

      (B)     PR interval >0.24 second  

      (C)     Demonstrated intolerance 

      (D)    Profound bradycardia or hypotension  

      (E)      A, C, and D

      (F)      All of the above  

Explanation:

The 2004 ACC/AHA guidelines recommend that all patients after STEMI except those with contraindications should receive beta-blocker therapy.[1] According to the guidelines, the following are considered relative contraindications to beta-blocker therapy in the acute phase: heart rate <60 bpm, systolic arterial pressure <100 mm Hg, moderate or severe LV failure, signs of peripheral hypoperfusion, shock, PR interval >0.24 second, second- or third-degree AV block, or reactive airway disease.[27] However, following the acute phase post- MI, beta-blockers are sufficiently important in STEMI that they should be withheld only in patients with absolute contraindications such as the following: high-grade heart block without pacemaker, demonstrated intolerance, profound hypotension or bradycardia, or severe reactive airway disease.

Question8

Which of the following are appropriate strategies to minimize fatigue and other side effects from beta-blocker therapy in this patient?

     (A)        Lower metoprolol dose

      (B)        Switch from short- to long-acting metoprolol 

      (C)        Switch to propranolol 

      (D)        Temporarily discontinue beta-blocker treatment  

      (E)        A and B

      (F)        A and C    

Explanation:

When initiating beta-blockers, slow upward titration to the minimum effective dose is a good strategy to minimize side effects, especially in patients with heart failure. [29] If full dose beta-blocker has been started and side effects occur, titrating slightly downward is certainly a better option than discontinuing the drug completely. In light of theoretical concepts suggesting reduced adverse effects associated with lower and less frequent peak concentrations, switching from short- to long-acting metoprolol is also a possible option. Switching to propranolol is probably not a good option since a quantitative review of randomized trials testing beta-blockers in patients with MI, heart failure, and hypertension (n≈35000) found a greater risk of fatigue with early-generation beta-blockers, such as propranolol and timolol, compared to later-generation beta-blockers, such as metoprolol or atenolol, P=.04).[16] However, switching a patient with suspected side effects to a different late-generation beta-blocker is another option. Discontinuation of the beta-blocker should only be considered after other options have been exhausted and the identified adverse effect is considered to outweigh the potential benefits of therapy.