What are the initial drugs that should be given to prevent the myocardial infarction from worsening?

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality risk in patients with myocardial infarction, especially in those with anterior infarction, heart failure, or tachycardia. The greatest benefit occurs in the highest-risk patients early during convalescence. ACE inhibitors are given > 24 hours after thrombolysis stabilization and, because of continued beneficial effect, may be prescribed long-term.

Angiotensin II receptor blockers (ARBs) may be an effective alternative for patients who cannot tolerate ACE inhibitors (eg, because of cough). Currently, they are not first-line treatment after myocardial infarction. Contraindications include hypotension, kidney failure, bilateral renal artery stenosis, and known allergy.

Statins (HMG-CoA reductase inhibitors) have long been used for prevention of coronary artery disease and ACS, but there is now increasing evidence that they also have short-term benefits, such as stabilizing plaque, reversing endothelial dysfunction, decreasing thrombogenicity, and reducing inflammation. Thus, all patients without contraindications (eg, statin-induced myopathy, liver dysfunction) to therapy should receive a statin at the maximally tolerated dose as early as possible following ACS regardless of their serum lipid levels.

PCSK-9 inhibitors (evolocumab, alirocumab) are used for patients not at target LDL-C levels. They are used alone or in combination with other lipid-lowering therapies (eg, statins, ezetimibe) for the treatment of adults with primary hyperlipidemia (including familial hypercholesterolemia).

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Tolerance to GTN (nitroglycerin) is mainly caused by oxidative inactivation of the reductase activity of ALDH2, which results in decreased GTN bioactivation, diminished levels of nitrite (NO2-) and nitric oxide (NO). This response abrogates the GTN-induced vasodilation phenomenon due to insufficient activation of soluble guanylate cyclase and production of cyclic guanosine monophosphate (cGMP) in the vascular smooth muscle. Besides its reductase activity, the dehydrogenase activity of ALDH2 is also down-regulated by GTN tolerance, leading to accumulation of toxic aldehydes (i.e. 4-hydroxy-2-nonenal; 4-HNE) inside the mitochondria, which further disrupts the mitochondrial respiratory chain and results in reactive oxygen species generation. GTN-mediated ALDH2 inactivation triggers apoptosis in cardiomyocytes as well as abolishes the vasodilator effect of GTN vascular smooth muscle.

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