Chapter 20: Chronic Stable Angina & Myocardial Infarction Therapy

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Welcome to the Deep Dive.

Today we're tackling a really core topic from advanced

pharmacotherapeutics, chronic stable angina, or CSA, and also myocardial infarction, MI.

This is bread and butter stuff for advanced practice, and it's got huge implications, not just clinically but economically too.

Cardiovascular disease costs are staggering,

and angina alone affects millions.

Millions.

It's huge.

So our goal today isn't just listing drugs.

No, definitely not.

We want to break down the why, why these drug classes, why these guidelines.

We're aiming for that clinical reasoning piece.

Okay, great.

Let's start at the beginning then.

Angina, what is it fundamentally?

Fundamentally, it's an imbalance.

The heart muscle needs more oxygen than the blood flow can actually deliver at that moment.

Simple as that, really.

Demand, outstrip, supply.

And right away, we have to make a key distinction, don't we, between stable and unstable?

Absolutely critical.

So stable angina is the kind that's predictable.

You know, it comes on with exertion, maybe stress, and importantly, it gets better with rest or some nitroglycerin.

Okay, predictable pattern.

Got it.

But then you have unstable angina, and this is where things get serious.

It's either new chest pain, pain that's getting worse, more frequent, or, and this is the big red flag pain that happens even when you're resting.

That's the one that screams high risk for MI.

Exactly.

That patient needs immediate attention.

And we also can't forget the

anginal equivalent.

That's a tricky one.

Oh, definitely.

Sometimes the heart's cry for oxygen doesn't manifest as typical chest pain.

It might just be shortness of breath when they exert themselves, maybe profound fatigue.

So you could miss it if you're only looking for that elephant on the chest feeling.

You absolutely could.

It requires sharp assessment skills.

Okay, before we even get to the drugs, we need to talk roots,

causes, risk factors.

Right.

The textbook lays them out clearly.

You've got the non -modifiable ones, things you can't change, like age, family history, gender,

remembering those average ages for first MI,

about 65 for men, 72 for women.

Yeah, can't change those.

But then there are the modifiable ones.

And that's where we focus our non -pharmacologic efforts.

Smoking, high blood pressure, high cholesterol, diabetes.

These are the big ones we can actually tackle.

And let's connect those directly.

How does something like smoking actually hurt the heart in this context?

It's not just long -term damage, is it?

No, it has immediate effects too.

Smoking acutely boosts catecholamines, think adrenaline.

So that pushes up heart rate, blood pressure,

increases the heart's workload right then and there.

Plus it makes platelets stickier, more likely to form clots.

It's bad news all around.

So all these roads, modifiable and non -modifiable, they sort of lead to the same place pathologically.

Pretty much.

Yeah.

The underlying process for almost all chronic stable angina is atherosclerosis, that gradual clogging of the arteries.

And the book describes it in stages, which is helpful.

Yeah, three stages.

First, the fatty streak.

This can actually start way back in childhood.

It's just these lipid -filled cells, macrophages mostly, accumulating on the artery wall.

No real blockage yet.

Okay, stage one.

Innocent enough sounding.

Then, maybe around age 30 or so, it progresses to stage two, the fibrous plaque.

Now you get a raised lesion.

It's got this fibrous cap over core of lipid.

And this starts to physically narrow the lumen, the inside of the artery.

Ah, so that's why stable angina happens with exertion.

The narrowed pipe can't handle the extra flow needed.

Exactly.

The plumbing can't keep up with demand.

And then stage three.

Stage three is the complicated lesion.

This plaque is nastier.

It might have calcium deposits.

There might be bleeding inside the plaque itself.

It's unstable.

And if that cap breaks.

That's the catastrophe.

If the fibrous cap ruptures, the body sees it as an injury.

Platelets rush in, a thrombus, a clot forms right there.

And boom, complete occlusion, myocardial infarction.

That's the sequence.

So our chronic drug therapy is all about managing that supplied man balance with the narrowed pipes we have.

And crucially, trying to prevent that plaque rupture.

Makes sense.

Okay, let's get into the drugs.

Where do we usually start?

The RAAAS system seems like a logical place.

It is.

So agents targeting the renin angiotensin aldosterone system, your ACE inhibitors, your ARBs, your aldosterone antagonists, they're foundational, especially for certain patient groups.

Right.

Not necessarily for stopping acute pain, but for long -term benefit.

Exactly.

The guidelines really push for these in patients with a low ejection fraction, meaning their heart pump is weak, less than 40%.

Also for patients with hypertension, diabetes, or chronic kidney disease alongside their angina.

Okay, mechanism.

How do they work?

ACE inhibitors first.

ACE inhibitors block the enzyme that converts angiotensin for us to angiotensin II.

Pretty straightforward.

And angiotensin II is the bad guy here.

Well, it's powerful.

It's a potent vasoconstrictor, squeezes blood vessels, and it tells the body to hold on to salt and water via aldosterone.

So blocking it.

You get vasodilation, less squeezing, that reduces the pressure the heart has to pump against, that's after load reduction.

And by reducing salt and water retention, you reduce the volume of blood returning to the heart, that's preload reduction.

Less work for the heart overall.

And ARBs.

ARBs achieve basically the same thing, but they work downstream.

They block angiotensin II from binding to its receptors.

Same net effect.

Less vasoconstriction, less fluid retention.

Got it.

Now adverse effects.

What do we need to watch for?

Okay.

Across all three of these RAE keys classes, the big one is potassium.

They can all cause hyperkalemia, high potassium levels.

You must monitor electrolytes.

Super important.

What about ACE inhibitors specifically?

The classic side effect is that annoying, dry, hacking cough.

And there's the rare, but very serious risk of angioedema.

That's swelling of the face, lips, tongue.

That's a medical emergency.

Right.

Definitely need to counsel patients on that.

And contraindications.

Big ones.

ACE inhibitors and ARBs are absolutely contraindicated in pregnancy.

Major fetal harm risk.

Also, ACE inhibitors specifically are contraindicated if someone has bilateral renal artery stenosis narrowing in the arteries to both kidneys.

Okay.

And the aldosterone antagonists.

Like sperinolactone.

Also watch potassium there.

They're contraindicated if potassium is already high.

And with sperinolactone specifically, you need to warn about gynecomastia breast enlargement in men.

Usually reversible, but still, patients need to know.

Good clinical pearls.

Okay.

Let's shift gears to the drugs people often think of first with angina.

Nitrates.

Yeah.

The originals.

Used for both acute attacks and chronic prevention.

Their mechanism is kind of cool because it hits things from two angles.

Okay.

Tell me more.

They cause vasodilation, widespread, peripheral arteries, veins, and importantly, the coronary arteries themselves.

So dilation everywhere.

How does that help?

The big effect, especially for symptom relief, comes from dilating the veins.

That causes blood to pool out in the periphery.

So less blood returns to the heart.

That drastically reduces preload, the volume the heart has to handle.

Ah, so instantly reduces the heart's workload.

Exactly.

And dilating the coronary arteries directly can also help improve oxygen supply a bit.

Okay.

So for an acute attack.

Sublingual nitroglycerin, NTG, is first line.

The little tablet or spray under the tongue works fast, like in one to five minutes.

And the patient instructions here are absolutely critical.

Right.

Savingly critical.

They need to sit down, rest, take one dose.

If the pain isn't gone in five minutes, take a second dose.

And D, call 911 or emergency services.

Immediately after that second dose, if there's no relief,

that timing is vital.

It could be an MI.

Okay.

What about using nitrates long -term for prevention?

We use long -acting forms.

Things like isorabidinitrate, ISDN,

isorabidmonitrate, ISMN, or the NTG patch.

Any quirks with those?

Yes.

A big one with the oral forms, ISDN and ISMN.

Their absorption from the gut can be really unpredictable if taken with food.

So the standard advice is empty stomach one hour before or two hours after meals.

That's a bit inconvenient.

It can be.

But the biggest issue with long -term nitrate use is tolerance.

The body stops responding.

Exactly.

The smooth muscles in the blood vessels just kind of get used to the drug and it stops working as well.

How do we prevent that?

You absolutely must have a daily nitrate -free period, usually 10 to 12 hours.

So typically patients take the patch off overnight, or they schedule their oral doses to allow that break.

Non -negotiable for efficacy.

Got it.

Side effects.

Directly related to the vasodilation.

Headache is very common, especially at first.

Flushing, dizziness.

And because the blood pressure drops, the body might try to compensate by speeding up the heart rate.

That's reflex tachycardia.

Reflex tachycardia.

Hmm.

That sounds like something another drug class might help with.

Precisely.

That leads us perfectly into beta blockers.

They are often the first -line choice for chronic stable angina, particularly exertional angina.

Why first -line?

How do they help?

They tackle the demand side of the equation.

They block beta -1 receptors primarily in the heart.

This slows down the heart rate and reduces the force of contractility.

Less speed, less force means less oxygen demand.

Okay.

Reduces demand.

Anything else?

Yes.

That slower heart rate has another benefit.

It increases the time the heart spends in diastole, the resting phase.

And that's when the coronary arteries actually fill with blood.

So slower rate, more filling time, potentially better oxygen supply too.

Ah, nice.

And you mentioned the reflex tachycardia from nitrates.

Right.

Beta blockers are perfect for countering that.

They put the brakes on the heart rate, preventing that compensatory speeding up that nitrates can cause.

They work really well together in that sense.

Synergy.

Okay.

But selecting a beta blocker isn't always simple, is it?

There's selectivity.

Yeah.

That's a key point.

Some beta blockers are cardio -selective, meaning they primarily target beta -1 receptors in the heart, metoprolol, atenolol, or common examples.

And that matters for patients with lung issues.

Exactly.

If a patient has stable, well -controlled asthma, or COPD, a cardio -selective agent might be safer, as beta -2 blockade in the lungs can cause bronchoconstriction.

Might be safer, but not guaranteed.

Correct.

Even cardio -selective agents can lose their selectivity at higher doses, so you still need to use them cautiously in patients with reactive airway disease.

Okay.

Contraindications are crucial here, too.

When can we absolutely not use a beta blocker?

Big ones.

Decompensated heart failure, meaning the patient is acutely fluid, overloaded, and struggling.

Also pre -existing slow heart rates, burning cardio, or significant heart block.

Makes sense.

What about diabetic patients?

Very important point.

Beta blockers can mask some of the key warning signs of hypoglycemia, low blood sugar, specifically tachycardia and tremor.

Sweating might still occur, but other signals are blunted, so patients need to be extra vigilant with blood sugar monitoring.

Okay, good to know.

And like nitrates, stopping them suddenly is bad news.

Extremely bad news.

Abrupt withdrawal can cause a rebound effect, a withdrawal syndrome.

This can include worsening angina, hypertension, even triggering an MI.

You must taper beta blockers slowly if they need to be stopped.

Wow, lots to consider.

So if beta blockers aren't suitable, or not enough, maybe calcium channel blockers.

Yeah, CCBs are another major class.

Their main action is inhibiting calcium entry into arterial smooth muscle cells.

Resulting in?

Vasodilation.

Primarily in the arteries.

This reduces afterload, the pressure the heart pumps against.

They'd have as much effect on veins compared to nitrates, so less impact on preload.

Okay, arterial dilation.

But there are different types of CCBs, right?

Yes, two main subtypes, and they behave quite differently.

First, you have the dihydropyridines.

Think amlodipine, nophedipine.

What do they do?

They are potent peripheral vasodilators, good at lowering blood pressure.

Because of this vasodilation, they might cause some reflex tachycardia, similar to nitrates.

Importantly, they don't significantly affect the heart's electrical conduction system.

Okay, dihydropyridines, potent vasodilators, no conduction effect.

What's the other type?

The non -dihydropyridines, that's verapamil and diltiasm.

And how are they different?

They do affect conduction.

They slow the heart rate down by slowing the signal through the AV node.

They also have some vasodilator effect, but generally less potent than the dihydropyridines.

Okay, so they slow the heart rate, like beta blockers.

Yes, which leads to a critical warning.

Verapamil, in particular, also has a more pronounced negative endotropic effect.

It reduces the heart's pumping strength.

So combining a non -dihydropyridines CCB with a beta blocker?

Can be very risky.

The additive effects on slowing heart rate and AV conduction can lead to severe bradycardia or even complete heart block.

Non -dihydropyridines are generally contraindicated in patients already having heart block, and you need extreme caution if combining with a beta blocker.

That sounds like one of the biggest potential drug interactions to watch for in this whole chapter.

It absolutely is, high stakes.

What about side effects for CCBs generally?

Because of the vasodilation, peripheral edema swelling in the legs and ankles is common, especially with dihydropyridines.

Also headache, flushing, and verapamil specifically is notorious for causing constipation.

Gingival hyperplasia, overgrowth of the gums, can happen too, though less common.

Alright, let's shift focus slightly towards preventing MIs and managing acute events.

Antiplatelets Crucial, if a patient has established coronary heart disease, antiplatelet therapy is almost always indicated to reduce the risk of clot formation leading to an MI.

And the cornerstone here is?

Aspirin.

Low dose aspirin, usually 75 -162 mg daily for chronic prevention.

Oh, how does it work again?

It irreversibly blocks an enzyme called KeOX1 in platelets, which prevents the formation of thromboxane A2, a substance that makes platelets aggregate or clump together.

Okay, makes platelets less sticky.

What about in an acute MI situation?

The dose and formulation change.

It's 162 -325 mg of chewable, non -enterocoded aspirin, given immediately.

Chewing helps it get absorbed really quickly through the lining of the mouth.

Chewable, higher dose, stat, got it.

But aspirin isn't always used alone, especially after an MI.

Correct.

We often use dual antiplatelet therapy, or DAPT.

This usually involves aspirin plus a P2Y12 inhibitor.

Like clopidogrel or ticar griller.

Exactly.

Those drugs block a different pathway of platelet activation involving ADP, so you're hitting platelet aggregation from two different angles.

And DAPT is typically used for how long?

Usually for up to 12 months after an MI, especially if a stent was placed.

It's also used if a patient has an aspirin allergy or contraindication.

Main downside of antiplatelets?

Bleeding, of course.

Bruising is common.

Aspirin can also cause dyspepsia or stomach upset.

Okay.

Now, in the heat of the moment, an acute MI,

specifically N -STEMI non -ST elevation MI, how do we assess risk quickly?

The T -TEMI risk score is a really useful bedside tool described in the text.

It gives points for various factors age over 65, having several traditional risk factors, prior coronary stenosis of 50 % or more, ST deviation on the EKG, severe angina symptoms recently, elevated cardiac biomarkers, aspirin use in the last week.

Okay.

A checklist, basically.

Yeah.

You add up the points.

Maximum of seven.

A higher score signifies higher risk of adverse events like death or recurrent MI.

And importantly, a higher score generally means the patient is more likely to benefit from an early invasive strategy, like going to the cath lab for angiography and possible intervention.

So it helps guide that urgent decision -making.

What other drugs might be used acutely?

Anti -coagulants are key.

Things like heparin or inoxaparin, a low molecular weight heparin.

They don't break down existing clots, but they prevent new clots from forming or the existing one from getting bigger while other treatments are initiated.

Okay.

Prevent clot growth.

And what about the actual clot busters?

Fibrinolytics.

Right.

Drugs like alteplase.

These actually dissolve existing clots.

But, and this is a huge but, they are generally reserved only for STEMI patients, the ST elevation MIs.

And only when they can't get to a cath lab quickly for PCI, percutaneous coronary intervention?

Exactly.

There's a narrow time window and they carry significant bleeding risks.

They're absolutely contraindicated if someone has active internal bleeding, recent stroke, recent surgery, things like that.

Big risks.

Okay.

So fibrinolytics are a very specific tool for a specific situation.

Let's quickly touch on one more drug before we synthesize the strategy.

Renolazine.

Rennexa.

Yeah.

It's kind of in its own category, usually considered adjunctive therapy.

Meaning you add it on if other things aren't cutting it.

Pretty much.

If a patient is on optimal doses of a beta blocker, maybe a CCB or a nitrate, and they still have angina symptoms, renolazine can be added.

And its mechanism is different.

Yeah.

It's thought to work by blocking the late inward sodium current in heart cells.

This indirectly reduces calcium overload inside the cells during ischemia, which helps the heart relax better and use oxygen more efficiently.

The cool thing is it does this without significantly lowering heart rate or blood pressure.

That's its main advantage.

It provides symptom relief without those hemodynamic effects, which is great if the patient is already borderline hypotensive or bradycardic from their other meds.

Okay.

Good option to have in the toolbox.

So let's put it all together.

Chronic stable angina management strategy.

All right.

Step one, always acute symptom relief.

That's short acting nitroglycerin for basically everyone with angina.

They need it on hand.

Got it.

Then chronic prevention.

Foundation is lifestyle modifications, diet, exercise, smoking cessation, plus usually low dose aspirin for secondary prevention if they have established CHD.

And the first line drug for prevention.

Generally, a beta blocker, assuming there are no contraindications.

They have good evidence for improving outcomes, especially post MI, and they directly address the exertional component of angina.

Okay.

Start with a BB, if that's not enough or contraindicated.

Then you consider adding or substituting.

You might add a calcium channel blocker or a long acting nitrate.

The choice between them depends on the patient's heart rate, blood pressure, LV function, and potential side effects.

So maybe add a dihydropyridine CCB if the heart rate is okay or even a bit low, or add a long acting nitrate.

Right.

Or if the beta blocker isn't tolerated, maybe switch to a CCB or long acting nitrate as model therapy, though BBs are generally preferred first.

And if they're still having symptoms on two drugs, that's when you might consider adding rinolazine as a third agent.

Okay.

And how often do these stable patients need follow -up?

Stable patients?

Maybe every two to six months.

You need to be asking specifically about their angina pattern, frequency, severity, triggers,

asking about medication side effects,

and checking adherence, which is huge.

And don't forget labs.

Definitely not.

Periodic checks of kidney function are vital, especially since some drugs like Atenolol are renally cleared and might need dose adjustments.

Checking electrolytes, particularly potassium with RAS agents, lipids, A1C for diabetics,

the usual comprehensive checks.

Wow.

We've covered a massive amount of ground.

From the nitty gritty of plaque formation.

To the complexities of nitrate tolerance and DAPT.

But the core goals stay the same.

Stop the acute pain, slow down the disease progression, prevent MIs, and help patients live longer, better lives.

And remember, the non -drug stuff lifestyle isn't optional.

It's the bedrock that supports everything else.

Absolutely.

indefinitely.

And patient education is paramount.

They need to know their symptoms, know their meds, and know exactly when to call for help.

So for you, the advanced learner listening to this, what's the big takeaway?

It's really about understanding the nuances, isn't it?

It really is.

It's knowing why you might choose a cardio -selective beta blocker for one patient, and why combining verapamil and medoprolol could be disastrous for another.

It's anticipating side effects, managing interactions.

Knowing the contraindications cold.

Exactly.

It's applying this detailed knowledge to the individual sitting in front of you.

Here's a final thought to chew on, connecting back to those patient adherence challenges.

We tell patients they must take a break from their nitrates every single day.

That 10 -12 hour nitrate -free interval for the drug to keep working.

Crucial for preventing tolerance.

But then for their beta blocker, we tell them they must never stop it abruptly because of the risk of severe rebound angina, or even an MI.

That's a tricky juxtaposition.

It really highlights the complexity, doesn't it?

We're asking patients to navigate these very specific, almost contradictory demands for different medications, all while managing a serious chronic condition.

It underscores how vital clear communication and patient partnership are in making these complex therapies work safely and effectively.

It's the real art behind the science.

That's a great point.

It really emphasizes the practice part of advanced practice pharmacology.

Indeed.

Well, thank you for joining us for this deep dive into chronic stable angina and mi -pharmacotherapeutics.

We hope this helps clarify these critical concepts.

Happy studying!