01-10-01

Does primary literature support the use of nifedipine for acute reductions on blood pressure?

In 1985, the Food and Drug Administration Cardiorenal Advisory Committee reviewed data regarding the safety and efficacy of sublingual nifedipine for hypertensive emergencies. The committee unanimously concluded that information was insufficient for the use of these agents in hypertensive emergencies. Therefore, the committee recommended the dismissal of this practice because there was no evidence to show that it was safe or efficacious.

In 1995, the National Heart, Lung, and Blood Institute released a statement regarding short-acting preparations of nifedipine. The statement warned doctors that a short-acting formulation of nifedipine should be "used with great caution (if at all), especially at higher doses, in the treatment of hypertension, angina, and myocardial infarction." The statement was based on the recommendations of the Ad Hoc Committee on Calcium Channel Blockers. The committee had convened to determined if the use of nifedipine was associated with an increased dose-dependent risk of death from myocardial infarction.2

In an article by Grossman et al., the objective was to determine the overall safety and efficacy of nifedipine for hypertensive emergencies. The authors noted that there was widespread use of nifedipine for hypertensive emergencies although there is not a labeled indication by the FDA. There were several reports of adverse effects, with documented cases of cerebrovascular ischemia, stroke, severe hypotension, acute myocardial infarction, conduction disturbances, fetal distress, and death. This data supports the conclusion that short-acting nifedipine preparations should not be used routinely in hypertensive emergencies and pseudoemergencies due to the seriousness of adverse effects and the complete lack of outcome data.1

In 1997, the JNC-VI guidelines for management of hypertension noted the common use of short-acting nifedipine preparations for acute reductions in blood pressure. However, JNC-VI guidelines listed nifedipine as an unacceptable choice for acute reductions in blood pressure due to reports of adverse effects and the inability to control the rate or degree of reduction on blood pressure when using these agents. 3

In an article by O'Meara et al., the authors retrospectively reviewed the records of patients with Stage 3 or 4 hypertension (SBP >180mm Hg or DBP > 110 mm Hg) who received immediate-release nifedipine from January 1994 through June 1994. The objectives were to determine the frequency of rapid, precipitous falls in blood pressure and to identify any serious adverse outcomes. The population consisted of 57 males and 46 females. Precipitous falls in blood pressure, defined as a change in SBP >50 mm Hg or a change in DBP >30 mm Hg, were observed in 44 patients. Serious adverse events that required intervention occurred in five patients. Because rapid reductions in blood pressure are rarely recommended, it was concluded that alternate pharmacological agents and therapies should be considered for patients with Stage 3 or 4 hypertension.4

The role of short-acting nifedipine in hypertensive urgencies was examined in a report by Sunderji et al. The report noted twelve cases of serious adverse events that had been reported with short-acting nifedipine preparations. Nine of the cases resulted in cardiac events (electrocardiographic changes in 4 patients, myocardial infarction in 4 patients, and complete heart block in 1 patient). Therefore, the use of short-acting sublingual or oral nifedipine for the treatment of hypertensive urgencies was not recommended.5

The review article, "The Diagnosis and Management of Hypertensive Crises" noted the widespread use of short-acting nifedipine for hypertensive emergencies, severe hypertension associated with chronic failure, perioperative hypertension, and pregnancy induced hypertension. The article recognized that sudden reductions in blood pressure with administration of nifedipine have resulted in myocardial ischemic events with fatal outcomes. The authors concluded that short-acting preparations of nifedipine should not be used for blood pressure control in patients with hypertensive crises.6

According to the package insert information approved by the FDA, there is a warning regarding the use of short-acting nifedipine for acute reductions in blood pressure. The package insert mentions well-documented cases of profound hypotension, myocardial
infarction, and death when short-acting preparations were used in this manner.7

Reference:
1. Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on nifedipine capsules in hypertensive emergencies and pseudoemergencies? JAMA. 1996; 276: 1328-1333.
2. Nifedipine: danger of short-acting formulations. Who Drug Information. 1995; 9:220-221
3. Joint National Committee on the Detection, Evaluation, and Treatment of Blood Pressure. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Archives of Internal Medicine. 1997; 157: 2413-2446
4. O'Meara JG, Wilson DJ. Sublingual and Oral Nifedipine for the Treatment of Severe Hypertension: Blood Pressure Reduction and Clinical Outcomes. Hypertension. 1997; 30:488
5. Sunderji R, Shalansky KF, Beauchesne MF, Frug A. Is There a Role for Nifedipine in Hypertensive Urgencies? Canadian Journal of Hospital Pharmacy. 1999; 52: 167-170
6. Varon J, Marik PE. The Diagnosis and Management of Hypertensive Crises. CHEST. 2000; 118: 214-227
7. Sifton DW. Physician's Desk Reference. 2000.