Editing Angina (section)

==Treatment==
{{Further|Antianginal}}

Angina pectoris occurs as a result of coronary blood flow insufficiency in the face of increased oxygen demand. The principal goal in the prevention and relief of angina is to limit the oxygen requirement of the heart so it can meet the inadequate oxygen supply derived through the blood supplied from the stenosed or constricted arteries. The main goals of treatment in angina pectoris are relief of symptoms, slowing progression of the disease, and reduction of future events, especially [[myocardial infarction|heart attacks]] and death. Beta blockers (e.g., [[carvedilol]], [[metoprolol]], [[propranolol]]) have a large body of evidence in morbidity and mortality benefits (fewer symptoms, less disability, and longer life) and short-acting [[nitroglycerin (medication)|nitroglycerin]] medications have been used since 1879 for symptomatic relief of angina.<ref>{{cite book|title=Drug discovery: a history|vauthors=Sneader W|year=2005|publisher=Wiley |isbn=978-0-471-89980-8}}{{page needed|date=February 2013}}</ref> There are differing course of treatments for the patient depending on the type of angina the patient has. However, this second can provide a brief overview of the types of medications provided for angina and the purpose by which they are prescribed.

[[Beta blocker]]s, specifically B1 adrenergic blockers without intrinsic sympathomimetic activity, are preferred for angina treatment, out of B1 selective and non-selective as well as B1 ISA agents. B1 blockers are cardioselective blocking agents (such as nevibolol, atenolol, metoprolol, bisoprolol, etc.) which result in blocking cAMP in the heart muscle cells. cAMP, which plays a vital role in phosphorylating the ryanodine receptor and LTCC, will usually increase Ca<sup>+2</sup> levels in the heart muscle cells, blocking contraction. Therefore, B1 blockade decreases the HR and contraction of the heart muscle, making it demand less oxygen. An important thing to note is that the B1 cardioselective blockers are cardioselective and not cardio-specific. This means that if the beta-adrenergic antagonist is prescribed in higher doses, it can lose the selectivity aspect and begin causing hypertension from B2 adrenergic stimulation of smooth muscle cells. This is why in therapy for patients with angina, the vasodilatory organonitrates complement the use of B-blockers when prescribed the use of angina. The preference for Beta-1 cardioselective blockers is for B1 cardioselective blockers without instrinsic sympathetic activity. Beta blockers with intrinsic sympathetic activity will still do the beta blockade of the heart muscle cells and have a decreased ionotrophic and chronotropic effect, but this effect will be to a lesser extent than if the beta blocker did not have the instrinsic sympathetic activity. A common beta-blocker with ISA prescribed for the treatment of angina is Acebutolol.

Non-selective beta-adrenergic antagonists will yield the same action on B1 receptors, however will also act on B2 receptors. These medications, such as Propranolol and Nadolol, act on B1 receptors on smooth muscle cells as well. B1 blockade occurs in the smooth muscle cells. Specifically cAMP is responsible for inhibiting Myosin Light Kinase, the enzyme responsible for acting on Actin-Myosin. The inhibition of B1 will result in decreased levels of cAMP which will lead to increased levels of  Myosin Light Chain Kinase in the smooth muscle cells, the enzyme responsible for acting on Actin-Myosin and leading to contraction of the smooth muscle cell. This increased contraction of the smooth muscle cell from B1 blockade is not desirable since it explains the hypertension that may arise with patients taking that medication.

[[Calcium channel blocker]]s act to decrease the heart's [[workload]], and thus its requirement for oxygen by blocking the calcium channels of the heart muscle cell. With decreased intracellular calcium, the calcium-troponin complex does not form in the heart muscle cell and it does not contract, therefore reducing the need for oxygen.

The other class of medication that can be used to treat angina are the organic nitrates. Organic nitrates are used extensively to treat angina. They improve coronary blood flow of the coronary arteries (arteries which supply blood to the heart muscle) by reversing and preventing vasospasm, which increases the blood flow to the heart, improving perfusion and oxygen delivery to the heart associated with the pain of angina. These drugs also reduce systemic vascular resistance, of both veins and arteries but the veins to a greater extent. The decrease in the resistance of the arteries and veins decreases the myocardial oxygen demand, which also reduces myocardial oxygen demand.  [[nitroglycerin (medication)|Nitroglycerin]] is a potent [[vasodilator]] that decreases myocardial oxygen demand by decreasing the heart's workload. Nitroglycerin should not be given if certain inhibitors such as [[sildenafil]], [[tadalafil]], or [[vardenafil]] have been taken within the previous 12 hours as the combination of the two could cause [[vasodilatory shock|a serious drop in blood pressure.]]

Treatments for angina are [[Angioplasty|balloon angioplasty]], in which the balloon is inserted at the end of a [[catheter]] and inflated to widen the arterial [[lumen (anatomy)|lumen]]. [[Stent]]s to maintain the arterial widening are often used at the same time. [[Coronary bypass surgery]] involves bypassing constricted arteries with venous grafts. This is much more invasive than [[angioplasty]].

Calcium channel blockers (such as [[nifedipine]] (Adalat) and [[amlodipine]]), [[isosorbide mononitrate]] and [[nicorandil]] are vasodilators commonly used in chronic stable angina.{{Citation needed| date=June 2009}} A new therapeutic class, called If inhibitor, has recently been made available: [[Ivabradine]] provides heart rate reduction without affecting contractility<ref name="pmid16451297">{{cite journal | vauthors = Sulfi S, Timmis AD | title = Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina | journal = International Journal of Clinical Practice | volume = 60 | issue = 2 | pages = 222–8 | date = February 2006 | pmid = 16451297 | pmc = 1448693 | doi = 10.1111/j.1742-1241.2006.00817.x }}</ref> leading to major anti-ischemic and antianginal efficacy. [[ACE inhibitor]]s are also vasodilators with both symptomatic and prognostic benefit. [[Statin]]s are the most frequently used lipid/cholesterol modifiers, which probably also stabilize existing atheromatous plaque.<ref name="doi:10.1001/jama.295.13.jpc60002">{{cite journal | vauthors = Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM | title = Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial | journal = JAMA | volume = 295 | issue = 13 | pages = 1556–65 | date = April 2006 | pmid = 16533939 | doi = 10.1001/jama.295.13.jpc60002 | doi-access = free }}</ref> Low-dose [[aspirin]] decreases the risk of heart attack in patients with chronic stable angina, and was part of standard treatment. However, in patients without established cardiovascular disease, the increase in [[hemorrhagic stroke]] and gastrointestinal bleeding offsets any benefits and it is no longer advised unless the risk of myocardial infarction is very high.<ref name="pmid20410163">{{cite journal | vauthors = Barnett H, Burrill P, Iheanacho I | title = Don't use aspirin for primary prevention of cardiovascular disease | journal = BMJ | volume = 340 | pages = c1805 | date = April 2010 | pmid = 20410163 | doi = 10.1136/bmj.c1805 | s2cid = 3137720 }}</ref>

Exercise is also a very good long-term treatment for the angina (but only particular regimens – gentle and sustained exercise rather than intense short bursts),<ref name="pmid8339420">{{cite journal | vauthors = Ades PA, Waldmann ML, Poehlman ET, Gray P, Horton ED, Horton ES, LeWinter MM | title = Exercise conditioning in older coronary patients. Submaximal lactate response and endurance capacity | journal = Circulation | volume = 88 | issue = 2 | pages = 572–7 | date = August 1993 | pmid = 8339420 | doi = 10.1161/01.CIR.88.2.572 | doi-access = free }}</ref> probably working by complex mechanisms such as improving blood pressure and promoting coronary artery collateralisation.

Though sometimes used by patients, evidence does not support the use of [[Traditional Chinese medicine|traditional Chinese herbal products]] (THCP) for angina.<ref>{{cite journal | vauthors = Zhuo Q, Yuan Z, Chen H, Wu T | title = Traditional Chinese herbal products for stable angina | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD004468 | date = May 2010 | volume = 2010 | pmid = 20464731 | pmc = 6718232 | doi = 10.1002/14651858.cd004468.pub2 }}</ref>

Identifying and treating risk factors for further coronary heart disease is a priority in patients with angina. This means testing for [[hypercholesterolemia|elevated cholesterol]] and other fats in the blood, [[diabetes mellitus|diabetes]] and [[hypertension]] (high blood pressure), and encouraging [[smoking cessation]] and [[weight loss|weight optimization]].

The calcium channel blocker [[nifedipine]] prolongs cardiovascular event- and procedure-free survival in patients with coronary artery disease. New overt heart failures were reduced by 29% compared to placebo; however, the mortality rate difference between the two groups was statistically insignificant.<ref name="pmid15351192">{{cite journal | vauthors = Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N, Just H, Fox KA, Pocock SJ, Clayton TC, Motro M, Parker JD, Bourassa MG, Dart AM, Hildebrandt P, Hjalmarson A, Kragten JA, Molhoek GP, Otterstad JE, Seabra-Gomes R, Soler-Soler J, Weber S | title = Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial | journal = Lancet | volume = 364 | issue = 9437 | pages = 849–57 | year = 2004 | pmid = 15351192 | doi = 10.1016/S0140-6736(04)16980-8 | collaboration = Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators | s2cid = 12795811 }}</ref>

===Microvascular angina in women===
Women with myocardial ischemia often have either no or atypical symptoms, such as palpitations, anxiety, weakness, and fatigue. Additionally, many females with angina are found to have cardiac ischemia, yet no evidence of obstructive coronary artery disease on cardiac catheterization. Evidence is accumulating that nearly half of females with myocardial ischemia have coronary microvascular disease, a condition often called microvascular angina (MVA). Small intramyocardial arterioles constrict in MVA causing ischemic pain that is less predictable than with typical epicardial coronary artery disease (CAD).

The pathophysiology is complex and still being elucidated, but there is strong evidence that endothelial dysfunction, decreased endogenous vasodilators, inflammation, changes in adipokines, and platelet activation are contributing factors. The diagnosis of MVA may require catheterization during which there is an assessment of the microcirculatory response to adenosine or acetylcholine and measurement of coronary and fractional flow reserve. New techniques include positron emission tomography (PET) scanning, cardiac magnetic resonance imaging (MRI), and transthoracic Doppler echocardiography.

Managing MVA can be challenging, for example, females with this condition have less coronary microvascular dilation in response to nitrates than do those without MVA. Females with MVA often have traditional risk factors for CAD such as obesity, dyslipidemia, diabetes, and hypertension. Aggressive interventions to reduce modifiable risk factors are an important component of management, especially smoking cessation, exercise, and diabetes management. The combination of non-nitrate vasodilators, such as calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors along with HMG-CoA reductase inhibitors (statins), also is effective in many women, and new drugs, such as Ranolazine and Ivabradine, have shown promise in the treatment of MVA. Other approaches include spinal cord stimulators, adenosine receptor blockade, and psychiatric intervention.<ref name="pmid27236120">{{cite journal | vauthors = Celik T, Ozturk C, Balta S, Demirkol S, Iyisoy A | title = Coronary microvascular dysfunction in patients with cardiac syndrome X: Ongoing debate | journal = International Journal of Cardiology | volume = 218 | issue = | pages = 233–234 | date = September 2016 | pmid = 27236120 | doi = 10.1016/j.ijcard.2016.05.050 }}</ref><ref name="pmid25555283">{{cite journal | vauthors = Cattaneo M, Porretta AP, Gallino A | title = Ranolazine: Drug overview and possible role in primary microvascular angina management | journal = International Journal of Cardiology | volume = 181 | issue = | pages = 376–81 | date = February 2015 | pmid = 25555283 | doi = 10.1016/j.ijcard.2014.12.055 }}</ref><ref name="pmid27245239">{{cite journal | vauthors = Lanza GA, Careri G, Stazi A, Villano A, De Vita A, Aurigemma C, Crea F | title = Clinical Spectrum and Outcome of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome and No Obstructive Coronary Atherosclerosis | journal = Circulation Journal | volume = 80 | issue = 7 | pages = 1600–6 | date = June 2016 | pmid = 27245239 | doi = 10.1253/circj.CJ-16-0145 | doi-access = free }}</ref><ref name="pmid25677893">{{cite journal | vauthors = Marinescu MA, Löffler AI, Ouellette M, Smith L, Kramer CM, Bourque JM | title = Coronary microvascular dysfunction, microvascular angina, and treatment strategies | journal = JACC. Cardiovascular Imaging | volume = 8 | issue = 2 | pages = 210–20 | date = February 2015 | pmid = 25677893 | pmc = 4384521 | doi = 10.1016/j.jcmg.2014.12.008  }}</ref><ref name="pmid27092288">{{cite journal | vauthors = Selthofer-Relatić K, Bošnjak I, Kibel A | title = Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice | journal = Cardiology Research and Practice | volume = 2016 | issue = | pages = 8173816 | date = 2016 | pmid = 27092288 | pmc = 4820617 | doi = 10.1155/2016/8173816 | doi-access = free }}</ref><ref name="pmid25760881">{{cite journal | vauthors = Titterington JS, Hung OY, Wenger NK | title = Microvascular angina: an update on diagnosis and treatment | journal = Future Cardiology | volume = 11 | issue = 2 | pages = 229–42 | date = March 2015 | pmid = 25760881 | doi = 10.2217/fca.14.79 }}</ref>

===Suspected angina===
Hospital admission for people with the following symptoms is recommended, as they may have unstable angina: pain at rest (which may occur at night), pain on minimal exertion, angina that seems to progress rapidly despite increasing medical treatment. All people with suspected angina should be urgently referred to a chest pain evaluation service, for confirmation of the diagnosis and assessment of the severity of coronary heart disease.<ref>{{cite web | work = NHS Clinical Knowledge Summaries | date = 2009 | url = http://www.cks.nhs.uk/angina/management/quick_answers/scenario_suspected_angina | title = Suspected angina | archive-url = https://web.archive.org/web/20101214040716/http://www.cks.nhs.uk/angina/management/quick_answers/scenario_suspected_angina | archive-date=December 14, 2010 | publisher = U.K. National Institute for Health and Clinical Excellence }}</ref>