Use of CCBs in Hypertension
The many available CCBs can be divided pharmacologically into two subgroups: dihydropyridines (e.g., nifedipine, amlodipine) and nondihydropyridines (e.g., verapamil, diltiazem). The latter typically have negative inotropic and chronotropic properties, whereas the former are more vasoselective and can increase heart rate, especially acutely if immediate-release preparations are given. All CCBs inhibit the flux of calcium into smooth muscle cells, resulting in vasodilation. Many CCBs are approved for patients with angina pectoris. Verapamil can cause dose-related constipation, and immediate-release dihydropyridine compounds can cause flushing, tachycardia, and dose-dependent pedal edema; only the latter is seen with long-acting preparations. The BP-lowering of CCBs is generally little affected by dietary sodium or NSAIDs. Although studies in the last millennium suggested that CCBs were associated with a significantly higher risk of cardiovascular events than other antihypertensive drug classes, recent meta-analyses of comparative clinical trials indicate that they are as effective in preventing both stroke and coronary heart disease as diuretics. The risk of heart failure is significantly increased (by about 44%) by CCBs, both dihydropyridine and nondihydropyridines. This may be due to diuretics’ ability to treat CHF symptoms as well as CCBs’ proclivity to cause congestive heart failure (CHF)-mimicking pedal edema. In addition, verapamil and diltiazem are able to reduce left ventricular ejection fraction.
