6.7 Cardiac Meds & Interventions like Stents and Bypass

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 This chapter includes stenting, angioplasty and coronary bypass surgery. Just scroll down

7. Heart Drugs and Interventions You Need to Know, Update 20 Aug. 2021

Blood Clotting : Aspirin, Anticoagulants, Thrombolysis Three processes involve in blood clotting and the clot's dissolution: 1) Blood platelet aggregation targeted to roughness in blood vessel wall; 2) Blood clot formation due to pro-clot chemical released during platelet aggregation; and 3) Dissolving the clot (Thrombolysis) by an enzyme that is stimulated by the clotting. So, the three classes of drugs: 1) Anti platelet-aggregation drug, e.g., aspirin, clopidogrel and its types; 2) anticoagulant like injected heparin, low molecular weight heparin and oral anti vitamin K drugs like coumadin a.k.a. Warfarin; and 3) Thrombolysins to dissolve blood clot.

Aspirin anti-aggregation platelet action is successful at doses as low as 30 mg per 24-hour. (The standard aspirin for headache is 325 mg pill.) Up until 2014, I took a quartered aspirin (81 mg) every day but upped it to 325 mg daily because of increased risk factor. If I have a bothersome ache, I take my daily aspirin to also help my ache.
   Another anti platelet drug is clopidogrel (Plavix). Clopidogrel's antiplatelet aggregation is additive to aspirin's so the two are being given together in high risk Coronary Artery Disease. For the usual primary prevention (a person without apparent CAD) low dose aspirin only may be used because the combination with clopidogrel, though it is a little more effective at prevention, may cause bleeding in brain and, given the low risk of CAD, the extra clopidogrel is not worth taking.

  

Anticoagulant heparin is to prevent further extension of blood clot and also against formation of clot in leg vein (Deep Vein Thrombosis), which may break off and travel to pulmonary artery in lung. Heparin is also used as adjunct with thrombolysis and balloon angioplasty/stent intervention. Recently, low-molecular weight heparin, e.g., enoxyparin, aka Lovenox, has proved useful for Deep Vein Thrombosis compared to the older heparin. Heparin is used during stenting in symptomatic CAD and only if no bleeding risk. It is more potent than aspirin to cause bleeding.

   Coumadin (Warfarin) is an oral anti-vitamin K anticoagulant that substitutes for injection anticoagulants like the heparins and is more popular because it is a pill. But it takes 24 hours to start to work and requires at least weekly blood test (a self testing kit available). It is the best and most convenient anticoagulant in atrial fibrillation and Deep Vein Thrombosis and for secondary prevention of symptomatic CAD. Note that Coumadin is the anticoagulant of choice out of hospital when high risk factor for thrombosis exists (atrial fibrillation, heart valve surgery). Always needs doc's supervision because the INR blood tests are needed to monitor dose.

Recently a number of new oral anti-clotting factor pills (eg, dibigatran, rivaroxaban) have become available but still small experience.

Thrombolysin: Overview of thrombolysis in 
Acute Myocardial Infarction shows injection of enzyme to dissolve clot in artery. Two types of injection compete – 1) intravenous into vein in arm and 2) direct delivery into obstructed coronary (or cerebral in stroke) artery via femoral artery-aorta/coronary artery catheter. The vein injection is simpler, less expensive and can be done fast by paramedic. This is important because minutes count. Good results can only be expected if thrombolysis is attempted within 3 hours of onset of first symptom – soonest best and the data for the second 3 hours show borderline success and after 12 hours, no success.

Thrombolysis via vein has higher hemorrhagic complication rate – a small incidence of hemorrhagic brain stroke seen after injection. High BP is contraindication to arm-vein thrombolysis. Artery catheter directly delivers thrombolysin to point of blockage, and very little gets into general circulation, but it has its own local complications like damage to heart wall and arteries. It is impractical as widespread procedure because of the time and expertise needed.

   When thrombolysis is delivered up front directly to the blocked artery, the competition is between it and balloon angioplasty/stent. Both the thrombolysis and the angioplasty with stent are done via catheter in coronary artery. (Heparin is used also.) In injection thrombolysis, the competitive trials show equal short-term result but higher stroke rate via arm vein.
   Thrombolysis does not improve the narrowing of artery as balloon angioplasty does. Long term results favor angioplasty/stent.

   Balloon angioplasty/stent has proved more useful and practical than front-loading thrombolysis but intravenous thrombolysis is useful when angioplasty/stent cannot be done immediately. These are decisions made by your cardiologist but you want to be sure that when you get unstable angina or MI you are taken to a cardiology service that can rapidly do both thrombolysis or angioplasty/stent. The only way to assure this is to check out places ahead, while you are healthy and then have a plan to get rapid transport (ideally within 60 minutes door to door from onset of angina pain to thrombolysis or angioplasty/stent).

Beta Blocker in 2021 is part of AMI treatment. (It is also very good treatment for low-grade hypertension and to keep a healthy, slow resting heartbeat rate, and as a preventive for atrial fibrilation and other arythmias) The beta-blocker reduces mortality and speeds recovery by slowing heart and reducing oxygen demand.

Nitroglycerin or Nitrates are famous as relievers of angina pain by tiny pill under tongue. They work by dilating the coronary arteries. But with severe CAD the arteries become too rigid to dilate and nitro pill will not prevent MI.
 Its main side effect is it drops BP so if you are taking nitro, sit or lie down if possible, and be prepared against fainting. As part of dropping BP it may speed heart, which is not good. Also it causes headache. Despite these, nitro under tongue or cream or ointment on chest is used on demand much by angina sufferer. In IV form it is used in ICU to drop very high blood pressure especially in CAD patient.

Angiotensin Converting Enzyme Inhibitor (ACE-I, or ACE-Inhibitor) is addition to cardiovascular, pro-longevity drugs. Angiotensin is a vascular reactive substance produced in the body. It has many functions and its metabolism intersects with a number of hormones and other neurotransmitters that are important in regulation of blood pressure, heartbeat rate and heart contraction power; and also in remodeling of heart and blood vessels, in renal function and in respiration. But it is enough to know that angiotensin is released in cells and liberated to plasma as angiotensin I, a form that has no vascular reactivity. Angiotensin I is normally acted upon by the angiotensin converting enzyme (ACE) which converts it to Angiotensin II, the form that has all the action. The ACE inhibitors all go under the name of drugs that end in “-pril”. (Captopril & Enalapril are the two most famous) The ACE-I are good additives to treatment of hypertension, heart failure, CAD and M.I. In fact, the ACE-I seem to be good for whatever ails the heart. (Furry pet owners are even giving the pill to prolong the lives of their beloved pets.) I have been taking one, Perindopril, in low dose 2 mg a day every morning for several years now and I expect to take it for life as part of my cardiovascular preventive healthy longevity program. The ACE-I meds have proven safe but occasionally cause a bothersome cough – due to release of an inflammatory agent. It is a temporary minor problem but when I do develop a cough I stop my ACE-I for the few days it takes for the cough to go away.

Angiotensin Receptor Blockers (ARB) have similar effects as ACE-I but the mechanism is a receptor block rather than an enzyme inhibition. They are more recent to use (most end in “artan” as “Losartan”); but seem as effective as ACE-I. Used where ACE-I has intolerable side effect.

Diuretics stimulate increased urination and are important in heart failure and also against high Blood Pressure.  They work by dehydrating the circulatory system and getting rid of NaCl salt from the system but too much of a good thing can become harmful if dose is too high, if wrong type diuretic, or if fluid intake low. Side effect of usual diuretic is low potassium (K⁺) causing muscle weakness. Diuretics usually end in "-ide" like chlorthiazide or "-one (say -own" like chlorthalidone. Diuretics are the anti-hypertensive used first line like beta-blockers and ACE-I and may be first choice when the other drugs cause problems.

Calcium Channel Blockers (CCB) are a group of medications that cause a relative block (slows passage) of Ca²⁺ ions from outside-of-cell's fluid to inside the cell, and cause slowing and weakening of the heartbeat. A CCB is used in place of beta blocker to slow heart without causing beta blocker side effect of increasing resistance to breathing. However it has its own problem of sparking heart arrhythmia, or dropping the BP too low, or causing heart failure. Never take nitrates with a CCB. (In 2004, the CCB replaced digitalis medication as leading cause of overdose death from heart medicine.) Beta blocker is safer for slowing heart. But CCB can be useful in arrhythmia and also as additive treatment of high BP.

Digitalis, used for centuries, strengthens heartbeat in heart failure and slows ventricular heartbeat in atrial fibrillation (AF). Today as Digoxin, it is still a main player in treatment of heart failure and regulation of AF but it has risk of complication and needs expert monitoring by cardiologist.

The adrenaline type neurohormones – norepinephrine, dobutamine - are used much in ICU (Intensive Care Unit) to up a dangerously low blood pressure – in heart attacks, brain strokes, and trauma blood loss, but in the last case with blood transfusion or fluid loading. Epinephrine (adrenaline) is used to reverse cardiac arrest or convert ventricular fibrillation to normal rhythm. It is standard in all CPR. Their blockers are the famous Beta-blockers that slow the heart and lower BP. They also slightly weaken heart muscle contraction but this effect usually ignored except in heart failure.

Percutaneous Transluminal Coronary Angioplasty (PTCA; a.k.a. Balloon Angioplasty a.k.a. PCI, or percutaneous coronary intervention) with stenting is a continuation of coronary angiography for the purpose of reopening and widening a narrowed or blocked segment of coronary artery and also of keeping the newly reopened, widened artery open. It has evolved greatly. It starts with intro by femoral artery puncture in thigh (alternative is use of arm artery) using a guiding hollow catheter that is advanced to entrance of main coronary artery. The catheter will serve as conduit in which interventional device(s) can be advanced and intermittent puff of x-ray contrast medium can be given to locate the device relative to the artery to be widened or opened.

Next a small (0.010-018 inch diameter) guide wire is pushed into the narrowed or blocked artery to just at the point of narrowing or blockage. The guide wire serves as a rail over which a therapeutic device is positioned. Then a balloon dilatation of the newly unblocked or narrowed artery segment is done. It is done by positioning an un-inflated tiny metal tip balloon in the narrowed segment and sharply inflated several times to widen the segment. A problem can be a collapse of the widening after a short time resulting in worse blockage. To remedy this, a stent (rigid hollow inner tube support) started to be used in 1994. In its most popular version, a slotted firm plastic tube is placed in the just widened narrow segment immediately in the time after balloon dilatation and the stent itself widens the narrowed segment and serves as firm support to prevent collapse of dilated wall while still allowing blood to flow forward. The latest coronary artery stents are made with special chemicals to prevent further atherosclerotic changes (DES, drug-eluting stent), or inflammation or blood clot. This has worked well and today all PTCA procedures leave drug-eluting stents.

   Another problem is breaking off material of a plaque and its passing further into the artery and blocking there. Also a problem is to open a completely blocked segment of artery. For that purpose an ‘atherectomy’ device that literally drills its way through the blocked artery has been developed and may be used and suction is applied to remove the cut-up plaque.

   In 2021 in medical centers with experienced team and latest equipment, PTCA is standard intervention for Acute Myocardial Infarction or unstable angina (worsening or newly occurring angina) and results are good. Almost all unstable angina patients are initially treated by PTCA with stenting. Exceptions are 1) when the main left coronary artery is >75% blocked (No angio because of  its high-risk of sudden death if the PTCA fails); 2) multiple smaller coronary artery obstructions that cannot be reached by PTCA.

Coronary Artery Bypass Grafting (CABG) Surgery is the most direct, effective method of repairing coronary narrowing and near-obstruction. It cannot restore damaged, scarred heart muscle but it can prevent it if done before the myocardial infarct has formed and can limit the infarct and slow down or eliminate heart failure. As with all things of value it has cost; today, 40+ years after first CABG in 1967, operative death has stabilized at 2 to 5%, and in well prepared case with best surgical team, <1%. The range of coronary heart disease for the surgery is wider than before and no longer limited by older age or poorer medical condition, although these factors increase mortality. But the easy availability of PTCA has taken the emergency edge off CABG and allowed better selection of cases under better pre-operative condition and therefore safer surgery as shown by the better results.

   CABG may be choice for severe multiple large vessel coronary disease, and in patient with major main coronary artery narrowing.

   Operation is normally performed on Cardio-Pulmonary Bypass heart-lung machine under hypothermia with stopped heart. Experimental procedure is being tried on beating hearts without heart-lung, with special instrument. Depending on findings at coronary angiography 1 to 5 bypasses may be done. Trend is to do maximal bypasses if narrowing justifies. The internal mammary artery of front chest wall is the best graft but limitation of its length in 4- or 5-vessel bypass usually requires at least 2 segments of saphenous vein (vein cut from anterior thigh). Anticoagulation during and post-op and anti-platelet medication long term is important. One should have a CABG done only at a top coronary surgical center! Find out which are the top centers before you need to use that knowledge.
   My Warning: Always keep in mind that the CABG surgery with Cardio-Pulmonary Bypass involves a major trauma to chest wall with many potentially serious side effects the worst of which are brain damage from pieces of blood clot released from the heart due to the Bypass and also the prolonged low blood pressure. Today PTCA with stent may be just as effective and less risky than CABG surgery, and CABG should be reserved for selected case, with independent second opinion and not rushed into in a panic. Getting PTCA does not prevent later CABG surgery so one is not competing with the other in an either/or choice, 
   When deciding on CABG surgery Go Slow! Go Slow! Go Slow! is my slogan.
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