The inciting event of acute MI is plaque rupture. Numerous factors, which are only partially understood, determine the occurrence of plaque rupture in a susceptible individual. Production of matrix metalloproteinases leads to degradation of the shoulder of a coronary plaque, resulting in exposure of its lipid-rich core to flowing blood (4,5,6). This triggers formation of platelet-rich thrombus. When the degree of thrombus is flow occlusive or platelet microemboli occlude distal flow, ischemia occurs, and myocardial stunning and necrosis follow.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert part of their benefit by decreasing the lipid content of plaques, rendering them less prone to rupture (7,8). Antithrombotic therapy decreases the tendency for occlusive thrombus formation; in particular, antiplatelet therapy decreases platelet aggregation at the site of ruptured plaque. Thus, in concert, statin therapy and antiplatelet therapy decrease the chance of MI occurring.

When occlusive thrombus has developed and caused ischemia for as little as 45 to 60 minutes, myocardium is irreversibly damaged. When this necrosis is transmural, the left ventricle may undergo a process called remodeling. This adaptation occurs at both the cellular level (destruction of connective tissue with slippage of myofilaments) and the whole-organ level (changes in the size and shape of the left ventricle) and results from adaptive (or maladaptive) mechanisms, such as apoptosis and fibroblast and myocyte hypertrophy triggered by increased wall stress from the inciting cellular changes (9). Angiotensin-converting enzyme (ACE) inhibitors greatly decrease this process of adverse remodeling, and it appears that angiotensin receptor blockers (ARBs) share this property. This explains, at least in part, the marked benefits of ACE inhibition or angiotensin receptor blockade among patients who have ventricular dysfunction after MI.

The zone of myocardium surrounding the infarcted area is particularly prone to electrical instability. This often manifests as premature ventricular contractions (PVCs) and predisposes the patient to ventricular arrhythmia. β-Blockers are useful in reducing the electrical irritability of the damaged myocardium. Implantable cardioverter-defibrillators (ICDs) are the best line of defense in treating electrical excitability that causes potentially lethal arrhythmia, particularly in the setting of impaired LV function.

Even if the LV muscle supplied by an occluded artery is dead, revascularization may still favorably effect ventricular remodeling and promote electrical stability. Depending on the duration of ischemia, among other factors, the myocardial cells either die or go into a state of hibernation. In this latter stage, revascularization can restore contractile functionality to what otherwise appears to be dead myocardium. Thus, there are a number of reasons, both established and theoretical, why vessel patency can improve prognosis (Fig. 21.1) (10).

Use of ACE inhibitors after acute MI is supported by a vast amount of evidence (Table 21.1) (67,68,69). The Acute Infarction Ramipril Efficacy study found that ramipril decreased mortality after MI among patients with heart failure (70), and the Survival and Ventricular Enlargement trial demonstrated the significant mortality benefit from administration of captopril after MI among patients with asymptomatic LV dysfunction (71). The Trandolapril Cardiac Evaluation study showed that the benefit of ACE inhibition persisted through 2 years of therapy, suggesting that ACE inhibition should be continued indefinitely (72). In fact, the results of the Heart Outcomes Prevention Evaluation (HOPE) study suggest that ACE inhibitors may be indicated in all patients who have had an MI (73). Further, the EUROPA trial also found a reduction in cardiovascular events in patients with stable coronary artery disease without LV dysfunction who were randomized to the ACE inhibitor perindopril versus placebo (74). However, the PEACE trial did not find a significant benefit of ACE inhibition with trandolapril versus placebo in patients with stable heart disease; this may reflect that the patients enrolled in this trial were lower risk than in the prior two trials (75).

Early initiation of oral ACE inhibitors is recommended for these patients, unless hypotension is present (76,77,78). However, the data do not support the early administration of IV ACE inhibitors (79). The early benefit of ACE inhibition on minimizing LV dilatation is most marked when reperfusion has not occurred, but other beneficial effects of ACE inhibitors likely apply to all patients (80). Despite these favorable data, ACE inhibitors are underprescribed after acute MI (81). Unless systolic blood pressure is lower than 100 mm Hg, ACE inhibition should generally be initiated within 24 hours of acute MI (78).

At present, ARBs appear to be an acceptable alternative to ACE inhibitors, particularly for patients who are unable to tolerate ACE inhibitors because of side effects such as cough. Whether any incremental benefit occurs with the addition of an ARB to the treatment regimen for patients who are on an ACE inhibitor has been evaluated in the Valsartan in Acute Myocardial Infarction Trial, which compared the ARB valsartan, the ACE inhibitor captopril, or the combination in MI patients with heart failure (82). In this population, there was no difference in mortality between the captopril and valsartan groups, and the combination did not provide any greater benefit than either agent alone, but did increase the incidence of drug-related side effects. However, in a more broad population of patients with systolic dysfunction in the Candasartan in Heart failure Assessment of Reduction in Mortality (CHARM)-Added trial, the ARB, candasartan, added to ACE inhibitor was found to be superior to the use of ACE inhibitor alone (83). Importantly, in the CHARM-Alternative Trial, Granger et al. (84) showed that candasartan alone reduced mortality and morbidity by nearly 30% among patients with systolic dysfunction but intolerant of ACE inhibitors, supporting the use of ARBs as an alternative to ACE inhibitors in ACE inhibitor intolerant patients.

The role of β-blockers in patients who have experienced MI is well established (Table 21.2) (85). Beneficial effects result from decreases in heart rate, blood pressure, myocardial oxygen demand, and arrhythmogenesis (86). Newer evidence suggests a favorable influence on LV remodeling as well (87). In aggregate, the data suggest that β-blockade reduces nonfatal MI by approximately 25%, which is paralleled by a 25% reduction in mortality (88,89). Although these data were gathered largely before the fibrinolytic era, TIMI II-B found that even in patients who had received fibrinolysis, compared with later administration of β-blockers, early β-blockade reduced recurrent chest pain and reinfarction (90). Furthermore, early β-blockade has been associated with a lower incidence of
intracranial hemorrhage after fibrinolysis (91). Conversely, in a secondary analysis from the GUSTO-1 trial database, Pfisterer et al. (92) raised concerns about the safety and efficacy of early IV β-blockade. In their analysis, they observed that patients treated with atenolol at any point were generally at lower risk, but that their adjusted 30-day mortality was significantly lower that those not receiving atenolol. However, patients treated with early intravenous then oral atenolol versus oral treatment alone had an increased odds of mortality (1.3; 95% confidence interval, 1.0–1.5; P = .02). Patients treated with IV atenolol had more heart failure, shock, recurrent ischemia, and pacemaker use than those treated with oral atenolol, but there were no significant differences in the rates of stroke, intracranial hemorrhage, and reinfarction. More recently, the COMMIT randomized trial also suggested that very early initiation of β-blockade was deleterious among patients who have a low blood pressure at admission and may be in impending cardiogenic shock (93). In COMMIT, early initiation of metoprolol increased the risk of cardiogenic shock, although it decreased recurrent infarction. Overall, though, there was no reduction in mortality. However, once patients were stabilized, β-blockers appeared to decrease the risk of sudden cardiac death. The lesson from these studies appears to be that in high-risk patients with hypotension or signs of heart failure, it is best not to initiate β-blockade, until the patient has stabilized.

β-Blockers remain underused after MI, sometimes because of unfounded concerns regarding relative contraindications such as diabetes or chronic obstructive pulmonary disease (94,95,96). β-Blockers have a similar relative benefit in the presence and absence of heart failure, although the absolute benefit is magnified in those with heart failure (97). Although numerous studies have confirmed the benefit and safety of β-blockade in the elderly, underuse remains a problem (98,99,100). The optimal dose of β-blockade in elderly patients, is not known, but doses lower than those that were used in several of the early randomized trials may be just as effective (101,102).

The limited available evidence suggests that β-blockade and ACE inhibition are complementary (103,104,105,106,107,108). In patients who experience congestive heart failure after MI, both classes of medication seem to be indicated. At the other end of the spectrum, in patients with normal LV function, perhaps only one of these classes of medication is needed. Without prospective data examining the incremental value of combination therapy, other patient factors, such as history of arrhythmia or diabetes, should also be considered in deciding which of these agents to use.

The Randomized Aldactone Evaluation Study found a 30% reduction in mortality among patients with severe heart failure randomized to spironolactone (109). Subsequently, the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study demonstrated a 15% reduction in mortality among patients with acute MI complicated by heart failure (110). However, without close monitoring, hyperkalemia can be a potentially lethal complication of aldosterone antagonism (111).

Given the abundance of mortality data supporting the use of ACE inhibitors and β-blockers, calcium channel blockers should not be considered first-line therapy in post-MI patients (112). The short-acting calcium channel blockers, especially nifedipine, should not be used for acute or chronic therapy, because these agents do not decrease mortality rates and appear to raise the risk of cardiac events (113,114,115,116,117). Without further supportive evidence, the main role of calcium channel blockers is for control of persistent hypertension in post-MI patients, or as primary therapy in the very rare patient with coronary artery spasm (118). The calcium channel blocker amlodipine does have strong data supporting its role as an antihypertensive and it appears to have a role in decreasing plaque regression and preventing cardiovascular events in patients with coronary artery disease without hypertension (119). Because it does not affect heart rate, it can be safely combined with a β-blocker.

No study has provided compelling evidence that nitroglycerin reduces mortality rates after acute MI. GISSI-3 found no mortality advantage or decrease in the incidence of LV dysfunction from the use of transdermal nitroglycerin (67). The Fourth International Study of Infarct Survival found no mortality benefit from use of an oral mononitrate preparation in any subgroup examined (68). Nevertheless, because of the acute antiischemic effect of these agents, every patient who has experienced an MI should be instructed to carry a bottle of sublingual nitroglycerin at all times and should be instructed in its safe use.

Statins are strongly indicated for use as secondary prevention after acute MI. The Cholesterol and Recurrent Events (CARE) trial demonstrated that pravastatin, compared with placebo, reduced the rate of death or MI in patients with previous MI (120). In addition to beneficial effects on reinfarction, the CARE study showed that statin use decreased the risk of stroke in survivors of acute MI (121,122). Several other trials have validated the role of statins in secondary and even primary prevention (123). Whether there are benefits specific to one statin over another remains to be elucidated. The Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 trial randomized over 4,000 patients with ACS to receive atorvastatin 80 mg/d versus pravastatin 40 mg/d for a mean duration of 24 months and demonstrated a 16% reduction in ischemic events with a more aggressive LDL cholesterol reduction strategy with atorvastatin 80 mg (124

Stay updated, free articles. Join our Telegram channel

Join