Coronary Artery Disease: Drug Therapy

Therapeutic targets

Therapy recommendations

Note: In patients with a high pretest probability (>85%), stenosing CAD should be assumed to be the cause of symptoms without further diagnosis and treatment planning should be started. Recommendations from the NVL “Chronic CHD” (unless further noted, only recommendations with recommendation grade A were included):

  • All patients with CHD should be treated with a statin (HMG-CoA reductase inhibitor) (first-line agent) to reduce morbidity (disease incidence related to a specific population) and mortality (death rate), regardless of baseline blood lipid (blood fat) levels. (Target value: LDL-C < 70 mg/dL (1.8 mmol/L); see below hypercholesterolemia/medical therapy).
  • All patients with stable CHD should receive 75-100 (-150) mg acetylsalicylic acid (ASA) per day; in case of ASA allergy, intolerance, or contraindications, ASA should be replaced by 75 mg clopidogrel daily
  • Patients with CHD and heart failure (cardiac insufficiency) should be treated with a beta-blocker for life (reduction in mortality assured for bisoprolol, carvediol, metoprolol succinate)
  • Patients with CHD and hypertension (high blood pressure) should be treated with antihypertensives (diuretics/dewatering drugs, beta-receptor blockers (beta-blockers), ACE inhibitors, long-acting calcium antagonists, angiotensin1 blockers (synonyms: sartans, AT1-receptor blockers)) whose efficacy in reducing cardiovascular events is established
    • Beta-blockers (first-line agents).
    • ACE inhibitors in patients with CHD and impaired systolic left ventricular function; if not tolerated, AT1 receptor blockers.
  • In patients with CHD and concomitant presence of left ventricular dysfunction (decreased ejection fraction), hypertension, or chronic kidney disease, ACE inhibitors and sartans (if ACE inhibitor intolerant) are recommended.Caution. Therapy with ACE inhibitors and sartan without the presence of the above comorbidities (concomitant diseases) does not reduce cardiovascular events (cardiovascular death, myocardial infarction / heart attack, apoplexy / stroke).
  • Patients with CHD and diabetes mellitus belong to a high-risk group that requires particularly strict risk management (see below Diabetes mellitus/Drug therapy).
  • Symptomatic therapy and prophylaxis of angina pectoris:
    • Beta-blockers (first-line agents); if beta-receptor blockers are intolerant or if antianginal effects are inadequate: ivabradine (if-ion channel blocker) alternatively ranolazine (piperazine derivative).
    • Long-acting calcium channel blockers (subordinate to beta blockers).
    • Fast-acting nitrate to cup (“suppress”) seizures (patients with stable angina).
  • After aortocoronary bypass surgery and need for anticoagulation (inhibition of blood clotting) should be continued postoperatively anticoagulation alone.
  • In acute coronary syndrome and aortocoronary bypass surgery, if anticoagulation is necessary, oral anticoagulation (OAK) should be continued postoperatively without platelet aggregation inhibition.
  • Hormone therapy should not be used for primary and secondary prevention of CHD.
  • Chelation therapy and phytotherapy should not be used for the treatment of CHD.
  • See also under “Other Therapy.”

Active substances (main indication)

Lipid-lowering agents: HMG-CoA reductase inhibitors (3-hydroxy-3-methylglutaryl coenzymeA reductase inhibitors; statins).

  • First-line agent for CHD by improving prognosis [NVL, as statins have been shown to reduce cardiovascular morbidity and mortality in persons with CHD]→ target values: LDL < 100 mg/dl (< 2.6 mmol/l), HDL > 40 mg/dl (> 1.9 mmol/l), triglycerides < 200 mg/dl (< 2.3 mmol/l)
  • Immediate administration in myocardial infarction (heart attack) is expected to improve prognosis by plaque stabilization

Antiplatelet drugs (TAH): acetylsalicylic acid (ASA), clopidogrel.

  • Acetylsalicylic acid is the first-line antiplatelet agent [All patients with stable CHD should receive 100 mg ASA; exception: stable CHD + atrial fibrillation (VHF) → limit oral anticoagulation and forgo antiplatelet agents].
  • Clopidogrel is used when ASA is not tolerated or contraindications to ASA are present
  • After elective coronary stent implantation (insertion of vascular stents into coronary arteries; bare metal stents, BMS), dual antiplatelet therapy (DAPT) is performed with ASA and clopidogrel. The duration of dual antiplatelet therapy is based on the patient’s bleeding risk.After coronary stent implantation and indication for oral anticoagulation, dual therapy of oral anticoagulation and an antiplatelet agent is recommended. If the ischemic risk is high, acetylsalicylic acid (ASA) may also be considered in triple therapy. Otherwise, triple therapy should be avoided or used only in the short term. Note: More severe bleeding under triple therapy.
  • In acute coronary syndrome and aortocoronary bypass surgery, oral anticoagulation without antiplatelet therapy should be continued postoperatively if anticoagulation is needed [NVL].Stent implantation in acute coronary syndrome: the combination of the more potent ADP-dependent antiplatelet agents prasugrel and ticagrelor with ASA should be preferred over the combination of ASA plus clopidogrel.

Beta-blockers – in heart failure (cardiac insufficiency) or post-myocardial infarction (myocardial infarction) condition; stable angina.

  • Patients after myocardial infarction should be treated with a beta blocker [NVL, due toreduction in mortality (death rate), documented for acebutuol, metoprolol succinate, propranolol, timolol]
  • Patients with CHD and heart failure should be treated with a beta-blocker for life (reduction in mortality assured for bisoprolol, carvedilol, metoprolol succinate).
  • Beta-receptor blockers should be used to reduce angina symptoms (“chest tightness”) and/or thereby improve exercise tolerance. They are first-line drugs because of the concomitant improvement in prognosis [NVL].
  • Beta-blockers and stable CHD: An international cohort study was able to show that in patients with stable CHD and more distant myocardial infarction (myocardial infarction) or without myocardial infarction, beta-blockers have the status of symptomatic therapy, as do calcium antagonists; a reduction in mortality (death rate) was not detectable in either case.
  • In stable CHD and intolerance/contraindications (contraindications) for beta blockers → long-acting calcium channel blockers, nitrates and nitrate analogues, ivabradine (see note below) or ranolazine.
  • If antianginal effect is insufficient → long-acting calcium channel blockers, nitrates and nitrate analogues, ivabradine, or ranolazine in combination.

ACE inhibitors – in arterial hypertension, heart failure, diabetes mellitus.

  • All patients with CHD and impaired systolic left ventricular function should be treated with an ACE inhibitor because of the documented reduction in morbidity (disease incidence related to a specific population) and mortality (death rate).
  • All patients with CHD and impaired systolic left ventricular function who cannot tolerate an ACE inhibitor should receive AT1 receptor antagonists (= angiotension II receptor antagonists).

Angiotension II receptor antagonists (AT-II-RB; ARB; angiotensin II receptor subtype 1 antagonists; AT1 receptor antagonists, AT1 antagonists; angiotensin receptor blockers, “sartans“).

  • First-line agent when AI versus ACE inhibitor[NVL: All patients with CHD and impaired systolic left ventricular function who cannot tolerate an ACE inhibitor should receive AT1 receptor antagonists (= angiotension II receptor antagonists)]
  • Dihydropyridine calcium channel blockers are contraindicated as monotherapy in the period up to 4 weeks after myocardial infarction and in unstable angina.
  • Caveat. ACE inhibitors and angiotensin II receptor antagonists should not be combined, because here increased renal dysfunction occurred

Calcium channel blockers – for stable angina pectoris.

  • Non-dihydropyridines are indicated for contraindications to beta blockers
  • Symptomatic therapy only, as not prognosis-improving; antiischemic, in beta-blocker intolerance.
  • Not in unstable angina, not until 4 weeks after myocardial infarction.

Nitrates – for angina pectoris

  • Only symptomatic therapy of CHD, as not prognosis-improving.
  • Patients with stable angina pectoris should have a fast-acting nitrate to cup attacks [NVL].

Sinus node inhibitor (for stable angina with sinus rhythm and AI against beta blockers).

  • SIGNIFY trial: ivabradine fails to halt progression (progression) of coronary artery disease in patients without heart failure. In patients with angina, the therapy harms

Further notes

  • Statin therapy:
    • Patients with NYHA II-IV heart failure should not be treated with statins.
    • LDL lowering to levels below 70 mg/dl did not further decrease cardiac events in patients with chronic ischemic heart disease in secondary prevention (population-based observational study of more than 31,600 CHD patients aged 30 to 84 years by an Israeli health organization).
    • Caution. Therapy monitoring is required: approximately 20% are non-responders, i.e., LDL levels cannot be lowered more than 15%:In a study with trials lasting one and a half to 2 years, LDL levels in responders decreased from an average of 131 to 73 mg/dl, whereas in hyporesponders they actually increased slightly from 96 to 101 mg/dl. This was also noticeable in plaque volume: while the proportion of vascular volume remained largely constant in responders, it had increased significantly in hyporesponders (+ 1.19 percentage points). Similarly, plaque regression (reduction of plaque volume fraction by ≥ 5%) occurred significantly less frequently in hyporesponders, 26% versus 38%, but progression occurred significantly more frequently (30% versus 14%).Non-responders and hyporesponders, respectively, were slightly younger than responders, more often male, and slightly more obese. They were less likely to have hypertension and less likely to receive beta-blockers. Mean statin doses were significantly lower in hyporesponders, which may partly explain the lack of treatment success.
    • In patients who still had elevated inflammatory parameters (high-sensitivity CRP > 2 mg/l) after high-dose statin therapy, therapy with an interleukin-1beta antibody canakinumab (dose of 150 mg every 3 months) resulted in a significant relative risk reduction for the combined endpoint of cardiovascular death, myocardial infarction, stroke.

Ranolazine (for stable angina)

Ranolazine (in stable angina) – An antiischemic mechanism of action of ranozalin appears to be improvement of coronary flow reserve (CFR). In type 2 diabetics and stable angina, ranolazine exerts its antianginal effects to a bes. degree; at the same time, HbA1c was reduced by 0.72 percentage points.

Coronary artery disease and diabetes therapy

Hypoglycemia (low blood glucose) can trigger ketcholamine-induced arrthythmias (cardiac arrhythmias); thus, prevention of hypoglycemia is a particular concern in CHD. Intensive HbA1c lowering increases this risk, especially in older diabetics and patients with previous coronary events! Caution is therefore advised in these patients when using sulfonylureas and glinides.A suitable drug in this patient group – especially in overweight patients – is metformin. Dipepdiyl peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues also provide hypoglycemia-free lowering.

Coronary artery disease and heart failure (heart failure)

  • CHD patients with concomitant heart failure should receive beta-blockers, ACE inhibitors, and, in the case of ACE inhibitor intolerance, AT1 receptor antagonists.
  • Note: Statins (cholesterol synthesis enzyme inhibitors) cause a 25-50% decrease in plasma coenzyme Q10 levels. In the absence of coenzyme Q10, the energy supply for the heart muscle is massively disturbed despite optimal substrate levels.
  • Patients with heart failure NYHA II-IV should not be treated with statins.
  • Clinical studies have repeatedly shown a clear association between decreased coenzyme Q10 levels and heart failure!(see below “Heart failure/Therapy with micronutrients” in relation to coenzyme Q10 substitution and heart failure).

Coronary artery disease and hyperhomocysteinemia

Folic acid supplementation can lead to significant improvement in endothelial dysfunction (dysfunction of the endothelium/inner layer of the vessels), as shown by flow-mediated dilation (widening) of the brachial artery in CHD patients.

Coronary artery disease and atrial fibrillation (AF)

In patients with stable CHD, that is, no clinical event such as acute coronary syndrome or stent implantation in the past 12 months, restriction to oral anticoagulation (OAC; inhibition of blood clotting) may be the sole antithrombotic therapy in the case of AF. After acute coronary syndrome or after percutaneous coronary intervention (PCI; see the term of the same name) with stent implantation, dual antiplatelet therapy (“dual antiplatelet therapy” by using two active principles to inhibit platelet aggregation, usually ASA (irreversible COX inhibitor) and clopidogrel (irreversible ADP receptor antagonist)) is indicated to prevent stent thrombosis. After coronary stent implantation and indication for oral anticoagulation, dual therapy of oral anticoagulation and an antiplatelet agent is recommended. If the ischemic risk is high, acetylsalicylic acid (ASA) may also be considered in triple therapy. Otherwise, triple therapy should be avoided or used only in the short term.

Coronary artery disease and supplements (dietary supplements; vital substances)

Appropriate dietary supplements should contain the following vital substances:

Note: The listed vital substances are not a substitute for drug therapy. Food supplements are intended to supplement the general diet in the particular life situation.