Amlodipine heart failure

The doxazosin arm was terminated early when a significantly higher risk of heart failure compared with chlorthalidone was observed." The other arms were continued as scheduled, and no significant differences in the primary end point were seen between chlorthalidone and either lisinopril or amlodipine. However, chlorthalidone had statistically fewer secondary end points than amlodipine (heart failure) and lisinopril (combined cardiovascular disease, heart failure, and stroke). The study conclusions were that chlorthalidone was superior in preventing one or more major forms of cardiovascular disease and was less expensive than amlodipine and lisinopril. 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

Packer M, O Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure, Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 1996 335 1 107-1 I 14. 

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance arterial dilators reduce systemic arteriolar resistance and decrease afterload. Nitrates (see p. 175) are commonly employed venous dilators for patients with congestive heart failure. If the patient is intolerant of ACE inhibitors, the combination of hydralazine and isosorbide dinitrate is most commonly used. Amlodipine and felodipine (see p. 188) have less negative inotropic effect than other calcium channel blockers, and seem to decrease sympathetic nervous activity. 

Amlodipine is a long-acting dihydropyridine calcium channel blocker. It has an adverse effects profile similar to those of other dihydropyridines, but at a lower frequency (1). Along with felodipine (2), but unlike other calcium channel blockers, it may also be safer in severe chronic heart failure when there is concurrent angina or hypertension (3). 

Vasodilatory calcium channel blockers have been reported to improve exercise tolerance in some preliminary studies. A multicenter, randomized, placebo-con-trolled trial was therefore performed in 437 patients with mild to moderate heart failure to assess the effects of amlodipine 10 mg/day in addition to standard therapy (5). Over 12 weeks amlodipine did not improve exercise time and did not increase the incidence of adverse events. 

Udelson JE, DeAbate CA, Berk M, Neuberg G, Packer M, Vijay NK, Gorwitt J, Smith WB, Kukin ML, LeJemtel T, Levine TB, Konstam MA. Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction. Am Heart J 2000 139(3) 503-10. 

Similarly, verapamil should be used with caution in patients with heart failure, and both diltiazem and nifedipine can cause problems in patients with poor cardiac reserve. However, the PRAISE study (18) suggested that amlodipine may be used safely, even in the presence of severe heart failure optimally treated with diuretics. 

O Connor CM, Carson PE, Miller AB, Pressler ML, Belkin RN, Neuberg GW, Frid DJ, Cropp AB, Anderson S, Wertheimer JH, DeMets DL. Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial Prospective Randomized Amlodipine Survival Evaluation. Am J Cardiol 1998 82(7) 881-7. 

In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), over 40 000 participants aged 55 years or older with hypertension and at least one other risk factor for coronary heart disease were randomized to chlortalidone, amlodipine, doxazosin, or lisinopril (1,2). Doxazosin was discontinued prematurely because chlortalidone was clearly superior in preventing cardiovascular events, particularly heart failure (2). Otherwise, mean follow-up was 4.9 years. There were no differences between chlortalidone, amlodipine, and lisinopril in the primary combined outcome or allcause mortality. Compared with chlortalidone, heart failure was more common with amlodipine and lisinopril, and chlortalidone was better than lisinopril at preventing stroke. 

Felodipine is a dihydropyridine derivative with diuretic properties (1). Its diuretic properties are not unique but are shared by other dihydropyridines. Its vasodilator-related adverse effects include flushing, headache, and tachycardia (2,3). Reduced arterial oxygen saturation has been seen in patients given intravenous felodipine for pulmonary hypertension (4,5). Along with amlodipine, but unlike other calcium channel blockers, felodipine may be safer in severe chronic heart failure accompanied by angina or hypertension. 

The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was the deciding evidence that the JNC7 used to justify thiazide diuretics as first-line therapy." It was designed to test the hypothesis that newer antihypertensive agents (an a-blocker, ACE inhibitor, and dihydropyridine CCB) would be superior to thiazide diuretic therapy. The primary objective was to compare the combined end point of fatal coronary heart disease and nonfatal myocardial infarction. Other hypertension-related complications (e.g., heart failure and stroke) were evaluated as secondary end points. This was the largest hypertension trial ever conducted and included 42,418 patients aged 55 years and older with hypertension and one additional cardiovascular risk factor. This prospective, double-blind trial randomized patients to chlorthalidone (a thiazide diuretic), amlodipine (dihydropyridine CCB), doxazosin (a-blocker), or lisinopril (ACE inhibitor) for a mean follow-up of 4.9 years. 

Adverse effects and contraindications of calcium channel blockers are described in Table 16. Verapamil, diltiazem, and first-generation dihydropyridines also should be avoided in patients with acute decompensated heart failure or LV dysfunction because they can worsen heart failure and potentially increase mortality secondary to their negative inotropic effects. In patients with heart failure requiring treatment with a calcium channel blocker, amlodipine is the preferred agent. ... 

Mozaffarian D. Anemia predicts mortality in severe heart failure The prospechve randomized amlodipine survival evaluahon (PRAISE). J Am Coll Cardiol 2003 41 1933-1939. 

A 38-year-old man was found in his bed deeply comatose and it was suspected that he had taken amlodipine 630 mg, zopiclone 300 mg, and uncertain amounts of citalopram and paracetamol at least 4 hours earlier. He was given activated charcoal, intravenous boluses of glucagon and calcium, and dopamine by infusion, followed by noradrenaline by infusion. Because of persistent hypotension and heart failure he was given levosimendan and the dobutamine was withdrawn. After 90 minutes his cardiac function had improved. The dose of levosimendan was increased and continued for 24 hours, when his lactic acidosis resolved. 

Some patients have characteristics that dictate compelling indications for certain drugs or combinations. Patients with hypertension and ischemic heart disease, diabetic nephropathy, or cardiac failure may benefit from combinations of drug classes that target both diseases. As hypertension is more common as patients get older, there are often multiple co-morbidities that influence the treatment options. In elderly men hypertension may co-exist with prostate disease, the latter being associated with a variety of lower urinary tract symptoms related to an overactive bladder and/or bladder outlet obstruction. Calcium channel blockers may have beneficial effects on the overactive bladder by reducing detrusor muscle tone, and this has been investigated in a trial of amlodipine plus terazosin compared with terazosin alone in men with mild to moderate hypertension and lower urinary tract symptoms [5 ]. Combination treatment was associated with notable improvement in overactive bladder symptoms and better control of hypertension. 

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