Clinical trial experience around the globe: Focus on calcium-channel blockers

Abstract

Summary:Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events.

The Inhibitory Effects of Ca2+ Channel Blocker Nifedipine on Rat Kv2.1 Potassium Channels

“…The dihydropyridines nifedipine, a Ca 2+ channel antagonist, is widely used as a medicine for a variety of cardiovascular diseases, such as hypertension [ 20 , 21 ] and angina pectoris [ 22 ]. Previous studies indicated that nifedipine also inhibited macroscopic currents through heterologously expressed human Kv1.5 [ 23 ] and rat Kv4.3 channels [ 24 ].…”

INCREASED VASCULAR SELECTIVITY AND PROLONGED PHARMACOLOGICAL EFFICACY OF THE L‐TYPE Ca2+ CHANNEL ANTAGONIST LERCANIDIPINE IN HUMAN CARDIOVASCULAR TISSUE

“…Various clinical trials have demonstrated the efficacy and safety of calcium channel blockers in the treatment of hypertension 1–4 . The so‐called ‘first‐generation’ calcium channel blockers, like nifedipine, are characterized by a poor vascular selectivity that leads to inotropic impairment, especially in situations of an already decreased cardiac function, or in situations where a combination with a beta‐blocker is desirable for the treatment of the patient 5–8 .…”

“…Various clinical trials have demonstrated the efficacy and safety of calcium channel blockers in the treatment of hypertension. [1][2][3][4] The so-called 'first-generation' calcium channel blockers, like nifedipine, are characterized by a poor vascular selectivity that leads to inotropic impairment, especially in situations of an already decreased cardiac function, or in situations where a combination with a beta-blocker is desirable for the treatment of the patient. [5][6][7][8] Furthermore, the fast onset and short duration of the pharmacological effects of the first-generation calcium channel blockers results in a compensatory activation of the sympathetic nervous system, 9 which may unfavourably influence the outcome of the patients.…”

Pharmacologic Agents in the Management of Hypertension—Nisoldipine Coat‐Core

“…Calcium antagonists are widely used for the treatment of hypertension alone or in combination with other classes of therapy. They are also quite heterogeneous; in addition to their blood pressure (BP)–lowering effects, some calcium antagonists may lower heart rate, improve symptoms of ischemic heart disease, induce regression of left ventricular hypertrophy, and mediate the regression of atherosclerosis 1–3 . Calcium antagonists are more effective in lowering blood pressure in African Americans than agents that block the renin‐angiotensin‐aldosterone system 4,5 …”

“…Among the calcium antagonist class, the drugs in the dihydropyridine subclass (amlodipine, felodipine, isradipine, nifedipine, and nisoldipine) are effective antihypertensive agents, are metabolically neutral, and their use has been shown to improve cardiac and cerebrovascular outcome in clinical trials 3 . In the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) 6 and the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT), 7 a calcium channel blocker‐based treatment regimen proved to be as effective as other regimens in reducing coronary heart disease morbitity and mortality.…”