Page 222 - Basic _ Clinical Pharmacology ( PDFDrive )

208 SECTION III Cardiovascular-Renal Drugs

is urgent stenting. However, prevention of ACS and treatment of
chronic angina can be accomplished in many patients with medical
therapy.
Because the most common cause of angina is atherosclerotic 175
disease of the coronaries, therapy must address the underlying
causes of CAD as well as the immediate symptoms of angina. In HR × BP ÷ 100
addition to reducing the need for antianginal therapy, such pri- 125 Control
120 mg/d
mary management has been shown to reduce major cardiac events 240 mg/d
such as myocardial infarction. 360 mg/d
First-line therapy of CAD depends on modification of risk
factors such as hypertension (see Chapter 11), hyperlipidemia 75 0 100 200 300 400
(see Chapter 35), obesity, smoking, and clinical depression. In Treadmill time (s)
addition, antiplatelet drugs (see Chapter 34) are very important.
Specific pharmacologic therapy to prevent myocardial infarction FIGURE 12–5 Effects of diltiazem on the double product (heart
and death consists of antiplatelet agents (aspirin, ADP receptor rate × systolic blood pressure) in a group of 20 patients with angina
blockers, Chapter 34) and lipid-lowering agents, especially statins of effort. In a double-blind study using a standard protocol, patients
(Chapter 35). Aggressive therapy with statins has been shown to were tested on a treadmill during treatment with placebo and three
doses of the drug. Heart rate (HR) and systolic blood pressure (BP)
reduce the incidence and severity of ischemia in patients during were recorded at 180 seconds of exercise (midpoints of lines) and at
exercise testing and the incidence of cardiac events (including infarc- the time of onset of anginal symptoms (rightmost points). Note that
tion and death) in clinical trials. ACE inhibitors also reduce the risk the drug treatment decreased the double product at the midpoint
of adverse cardiac events in patients at high risk for CAD, although during exercise and prolonged the time to appearance of symptoms.
they have not been consistently shown to exert antianginal effects. In (Data from Lindenberg BS et al: Efficacy and safety of incremental doses of diltiazem
patients with unstable angina and non-ST-segment elevation myo- for the treatment of angina. J Am Coll Cardiol 1983;2:1129.)
cardial infarction, aggressive therapy consisting of coronary stenting,
antilipid drugs, heparin, and antiplatelet agents is recommended. drug groups. Ranolazine or ivabradine (off-label), combined with β
The treatment of established angina and other manifestations blockers, may be effective in some patients refractory to traditional
of myocardial ischemia includes the corrective measures previously drugs. Most experts recommend coronary angiography and revas-
described as well as treatment to prevent or relieve symptoms. cularization (if not contraindicated) in patients with stable chronic
Treatment of symptoms is based on reduction of myocardial oxy- angina refractory to three-drug medical treatment. In the future,
gen demand and increase of coronary blood flow to the potentially agents such as allopurinol or perhexiline may be useful in patients
ischemic myocardium to restore the balance between myocardial who are not candidates for revascularization.
oxygen supply and demand.
Vasospastic Angina
Angina of Effort Nitrates and the calcium channel blockers, but not β blockers,
Many studies have demonstrated that nitrates, calcium channel are effective drugs for relieving and preventing ischemic episodes
blockers, and β blockers increase time to onset of angina and in patients with variant angina. In approximately 70% of patients
ST depression during treadmill tests in patients with angina of treated with nitrates plus calcium channel blockers, angina attacks
effort (Figure 12–5). Although exercise tolerance increases, there are completely abolished; in another 20%, marked reduction of
is usually no change in the angina threshold, ie, the rate-pressure frequency of anginal episodes is observed. Prevention of coronary
product at which symptoms occur. artery spasm (with or without fixed atherosclerotic coronary artery
For maintenance therapy of chronic stable angina, β blockers, lesions) is the principal mechanism for this beneficial response. All
calcium channel-blocking agents, or long-acting nitrates may be presently available calcium channel blockers appear to be equally
chosen; the drug of choice depends on the individual patient’s effective, and the choice of a particular drug should depend on
response. In hypertensive patients, monotherapy with either slow- the patient. Surgical revascularization and angioplasty are not
release or long-acting calcium channel blockers or β blockers may indicated in patients with variant angina.
be adequate. In normotensive patients, long-acting nitrates may be Unstable Angina & Acute Coronary
suitable. The combination of a β blocker with a calcium channel
blocker (eg, propranolol with nifedipine) or two different calcium Syndromes
channel blockers (eg, nifedipine and verapamil) has been shown to In patients with unstable angina with recurrent ischemic episodes
be more effective than individual drugs used alone. If a dihydro- at rest, recurrent platelet-rich nonocclusive thrombus formation
pyridine is used, a longer-acting agent should be chosen (amlodip- is the principal mechanism. Aggressive antiplatelet therapy with a
ine or felodipine). If response to a single drug is inadequate, a drug combination of aspirin and clopidogrel is indicated. Intravenous
from a different class should be added to maximize the beneficial heparin or subcutaneous low-molecular-weight heparin is also
reduction of cardiac work while minimizing undesirable effects indicated in most patients. If percutaneous coronary intervention
(Table 12–7). Some patients may require therapy with all three with stenting is required (and most patients with ACS are treated