Discussion On Whether Diltiazem Can Be Used To Treat Variant Angina

Rationale: Angina is pain caused by vasoconstriction of the coronary arteries that supply the myocardiocytes During an episode of angina, transient myocardial ischemia occurs due to increased myocardial oxygen consumption, which can lead to arrhythmias or heart attacks. Prinzmetal’s variant angina is a type of angina that is distinguished by repeating events of angina that occurs at night between midnight and early morning. Normal angina contrasts variant angina because it is typically initiated by physical exertion. Typical treatment for normal angina is diltiazem which is a calcium antagonist drug. 2 It works by blocking calcium release needed for myocardiocyte contraction and potentially vasodilates large coronary arteries. Furthermore, diltiazem inhibits the vasoconstriction of coronary arteries and potentially vasodilates the coronary arteries which prevents variant angina attacks. Although it is not FDA approved for variant angina, it is being considered for treatment.

Discussion: Typical treatment for variant angina is nitroglycerin as which stimulates myocardiocyte relaxation and reduces cardiac oxygen supply. Likewise, diltiazem also works to decrease myocardiocyte contraction to treat variant angina. Yasue H, et al. , conducted a clinical trial using 26 patients had variant angina and responded to ischemic events based on electrocardiogram values. The patients had to satisfy several exclusion criteria which included anginal attacks that occurred at rest, responded promptly to nitroglycerin, showed ischemic results in the electrocardiogram during an attack, had normal lab values of creatine phosphokinase, serum oxaloacetic transaminase, lactic dehydrogenase and had no severe complications.

The patients in this clinical trial were then divided into two groups. Group 1 had variant angina where the ST segment was elevated in the electrocardiogram during the angina attack. Meanwhile, group 2 had variant angina where the ST segment was depressed in the electrocardiogram during the angina attack. Patient were monitored for angina attacks from midnight to early morning and then the electrocardiogram reported the results of the attacks. Patients were given propranolol, diltiazem, dipyridamole, and atropine sulfate for 5 days to establish a control. After 5 days, each drug was then administered individually for 2-9 consecutive days and then the researchers measured the amount of transient ischemic changes in the electrocardiogram, which was relieved promptly with nitroglycerin.

The studies then measured the effectiveness of each medication by whether the attack was suppressed. Complete suppression of the attack indicated that the drug was effective. Reduction in attack frequency by less than one-third meant that the drug was moderately effective. Furthermore, a reduction of less than one-half meant that the drug was mildly effective. Lastly, if the attack frequency did not meet any of these criteria, then the drug was deemed ineffective. The researchers determined that diltiazem was completely effective for all 26 patients in completely suppressing the angina attacks.

There are some limitations for the study as the patients had to meet several exclusion criteria which were already listed. These exclusion factors are problematic as they do not show the efficacy of diltiazem in real world situations which means that further clinical trials need to be conducted to see the efficacy in real-world patients. Another factor that limited external validity was that all medications were stopped 5 days prior to the study except nitroglycerin and digestives. In the real world, patients would typically be on many other medications and these medications might impact the effect of diltiazem. Furthermore, the study was done Japan which may have some implications for external validity as the Japanese people have different lifestyles and diets compared to Americans.

Some strengths of the trial included that diltiazem was compared to multiple other medications which further illustrated its superiority in effectiveness. Furthermore, they excluded other severe complications such as CHF and COPD, which decreases the effects of confounding variables. Another strength is that they established a control by giving patients multiple medications to see what an effective treatment outcome looked like. This set the bar to what the researchers compared the individual treatments to.

Population: Patients with variant angina with ages ranging from 45-71 which had to meet 5 exclusion criteria which are listed above in the discussion.

Dosing studied: The doses of drugs discovered propranolol 80-100mg, diltiazem 120-180mg, dipyridamole 100mg, atropine sulfate 100mg and 1. 2mg.

Risk/Benefit (risk of adverse effects): As illustrated by this study, diltiazem has been shown as a treatment for variant angina. However, its side effects include headache, erythematous rash, and dry mouth. Diltiazem has many drug interactions including CCB, beta blockers and cardiac glycosides which are medications typically used in patients with cardiovascular issues.

Conclusion

Diltiazem was found to be superior in suppressing variant angina compared to the other medications in the trial by preventing vasoconstriction of coronary arteries and potentially vasodilating coronary arteries as well. However due to the study’s lack of external validity further clinical trials need to be conducted to determine the real-world effectiveness of diltiazem in variant angina.