Evaluation of Therapeutic Efficacy

M. MOHSEN IBRAHIM, MD
Prof. of Cardiology- Cairo University
President of the Egyptian Hypertension Society

·         Amelioration of myocardial ischemia

·         Improvement of quality of life

·         Decrease in cardiovascular morbidity

·         Prolonging survival

Therapeutic Efficacy

Therapeutic efficacy of both pharmacologic and interventional approaches has increased significantly in the past decade. The use of angiotensin- converting- enzyme inhibitors (ACE-I), anticoagulants (coumadin), newer antiplatelets (clopidogrel and glycoprotein IIb/ IIIa receptor antagonists), antithrombotics (low molecular weight heparin), aggressive blood lipid lowering with statins and wide use of aspirin have altered the landscape of the medical therapy of CAD. On the other hand, the introduction of newer antithrombotic regimens with PCI (e.g. Gp IIb/ IIIa inhibitors) and newer devices that reduce the rate of restenosis (e.g. intracoronary stents) have improved the efficacy of interventional therapy.

In patients with CAD the therapeutic efficacy of medical or interventional approaches is evaluated according to its ability to achieve the following:

·         Amelioration of myocardial ischemia.

·         Improvement of quality of life.

·         Decrease in cardiovascular morbidity.

·         Prolonging survival.

·         Myocardial Ischemia

Suppression of myocardial ischemia is an important goal of therapeutic policy. This goal can be defined both subjectively and objectively:

1. Relief of angina:

1.       Reduction in number of nitroglycerin tablets used by the patient.

2.       Improvement in exercise capacity and effort tolerance.

3.       Percentage of patients who have improvement or have complete relief of anginal pain.

2. Objective evidence of relief of myocardial ischemia

1.        Stress ECG:

Successful therapy will increase the exercise duration and exercise time to ischemia.

The following parameters are assessed during treadmill exercise ECG when evaluating effects of therapy:

a.       Exercise capacity: duration of exercise and measurement of metabolic equivalents (METs). One MET is defined as 3.5ml oxygen uptake/kg/minute, which is the oxygen uptake in a sitting position. Less than 5 METs indicate poor exercise capacity. For each MET increase in exercise capacity there is 12% improvement in survival.

b.       Exercise induced angina: onset of angina (after how many minutes of exercise) and its severity (non-limiting or limiting exercise continuation).

c.       ST-segment depression: extent and time to ST-segment depression.

d.       Duke scoring system: combines the previous three parameters in order to improve the diagnostic value of exercise testing.

Duke Treadmill Score (DTS): (exercise time in minutes) – (5 X ST-segment deviation in mm) – (4 X anginal index) -  (0: no angina; 1:non-limiting angina, 2: exercise limiting angina). Low risk means DTS greater than 5, moderate risk means DTS between 5 and minus 10, while high risk DTS is less than minus 10. 

2.       Nuclear myocardial perfusion imaging (MPI)

-          SPECT thallium-201 or technetium-based perfusion imaging.

-          Quantification of the perfusion defect during peak exercise [treadmill, bicycle, or pharmacologic intervention (adenosine or dipyridamole)] and 4-hours later.

-          Patients with moderately or severely abnormal scan have a higher rate of both cardiac death and myocardial infarction.

-          MPI can be used to determine which patients with stable angina are more likely to have a survival benefit from revascularization as opposed to medical therapy. At two years, mortality was significantly lower with medical therapy in patients with ischemia of <  10 percent of total myocardium while it was significantly lower with revascularization in patients with ischemia >10 percent of total myocardium.

3.       Hotler ECG- Montoring

Effect of therapy on attenuating prolonged ST-depression on ambulatory Holter monitoring.

·         Improvement in Quality of Life

-          Assessed usually through standardized questionnaire.

-          Provisional idea obtained by asking patient about job performance, job satisfaction, leisure time activity, care of family and children, marital relations.

·         Decrease in Cardiovascular Morbidity

Effects of therapy on the following morbidity events:

-          Development or reoccurrence of myocardial infarction.

-          Development of recurrent or refractory angina.

-          Rehospitalization for unstable angina or NSTEMI.

-          Need for PCI.

-          Need For CABG.

-          Stroke.

·         Prolonging Survival

-          Decrease in mortality is possibly the most important goal of any therapeutic intervention in patients with CAD.

-          Effects of intervention on both total mortality (death from any cause) and cardiac mortality (death due to cardiac causes) are evaluated.