FIGURE 12–5 Effects of diltiazem on the double product (heart rate × systolic blood pressure) in a group of 20 patients with angina of effort. In a double-blind study using a standard protocol, patients were tested on a treadmill during treatment with placebo and three doses of the drug. Heart rate (HR) and systolic blood pressure (BP) were recorded at 180 seconds of exercise (midpoints of lines) and at the time of onset of anginal symptoms (rightmost points). Note that the drug treatment decreased the double product at the midpoint during exercise and prolonged the time to appearance of symptoms. (Data from Lindenberg BS et al: Efficacy and safety of incremental doses of diltiazem for the treatment of angina. J Am Coll Cardiol 1983;2:1129.) drug groups. Ranolazine or ivabradine (off-label), combined with β blockers, may be effective in some patients refractory to traditional drugs. Most experts recommend coronary angiography and revascularization (if not contraindicated) in patients with stable chronic angina refractory to three-drug medical treatment. In the future, agents such as allopurinol or perhexiline may be useful in patients who are not candidates for revascularization.
Nitrates and the calcium channel blockers, but not β blockers, are effective drugs for relieving and preventing ischemic episodes in patients with variant angina. In approximately 70% of patients treated with nitrates plus calcium channel blockers, angina attacks are completely abolished; in another 20%, marked reduction of frequency of anginal episodes is observed. Prevention of coronary artery spasm (with or without fixed atherosclerotic coronary artery lesions) is the principal mechanism for this beneficial response. All presently available calcium channel blockers appear to be equally effective, and the choice of a particular drug should depend on the patient. Surgical revascularization and angioplasty are not indicated in patients with variant angina.
In patients with unstable angina with recurrent ischemic episodes at rest, recurrent platelet-rich nonocclusive thrombus formation is the principal mechanism. Aggressive antiplatelet therapy with a combination of aspirin and clopidogrel is indicated. Intravenous heparin or subcutaneous low-molecular-weight heparin is also indicated in most patients. If percutaneous coronary intervention with stenting is required (and most patients with ACS are treated
TABLE 12–7 Effects of nitrates alone and with a blockers or calcium channel blockers in angina pectoris.
Beta Blockers or Calcium Combined Nitrates with Beta Blockers Nitrates Alone Channel Blockers or Calcium Channel Blockers 1Baroreceptor reflex.
Note: Undesirable effects are shown in italics.
with stenting), glycoprotein IIb/IIIa inhibitors such as abciximab should be added. In addition, therapy with nitroglycerin and β blockers should be considered; calcium channel blockers should be added in refractory cases for relief of myocardial ischemia. Primary lipid-lowering and ACE-inhibitor therapy should also be initiated.
Atherosclerosis can result in ischemia of peripheral muscles just as coronary artery disease causes cardiac ischemia. Pain (claudication) occurs in skeletal muscles, especially in the legs, during exercise and disappears with rest. Although claudication is not immediately life-threatening, peripheral artery disease (PAD) is associated with increased mortality, can severely limit exercise tolerance, and may be associated with chronic ischemic ulcers, susceptibility to infection, and the need for amputation.