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HIGH BLOOD PRESSURE

November 10, 2004

High blood pressure, or hypertension, is a major contributing factor to the development of strokes, heart attacks, kidney disease, and circulation disorders. Elevated cholesterol levels can also result in an increase in heart attacks and strokes. Heart disease and stroke remain the first and third leading causes of death in the United States. More than 33 million Americans are estimated to have high blood pressure; this includes more than 14 million persons between the ages of 45 and 64.[1]...

High blood pressure, or hypertension, is a major contributing factor to the development of strokes, heart attacks, kidney disease, and circulation disorders. Elevated cholesterol levels can also result in an increase in heart attacks and strokes. Heart disease and stroke remain the first and third leading causes of death in the United States. More than 33 million Americans are estimated to have high blood pressure; this includes more than 14 million persons between the ages of 45 and 64.[1] Many people with increased blood pressure also have other risk factors such as elevated cholesterol, diabetes, and smoking. But many do not. Conversely, many people with higher cholesterol levels also have high blood pressure, smoke, or are diabetic, but many have only elevated cholesterol levels. In addition, the risk of cardiovascular disease—such as heart attacks and strokes—increases with age. Thus, it is extremely important to look at the global risk of cardiovascular disease rather than focusing on just the blood pressure or just the cholesterol level.[2]

High Blood Pressure in Pregnancy

Antihypertensive drugs may directly or indirectly harm the fetus. If the maternal placental circulation is reduced by lowering the mother’s blood pressure too much, there is the danger of immediate harm to the fetus by depriving it of an adequate supply of blood and thus of essential nourishment.

The Merck Manual[3],[4] recommends that women with preexisting mild hypertension (140/90 to 150/100 millimeters of mercury) discontinue antihypertensive drugs as soon as pregnancy is confirmed and monitor their blood pressure regularly. For patients with preexisting moderate hypertension (150/100 to 180/110 millimeters of mercury), methyldopa (ALDOMET) is the drug of choice. Women with severe hypertension (greater than or equal to 180/110 millimeters of mercury) represent a much more complicated medical condition in which less desirable drugs may be appropriate.

Leg Swelling (Edema) in Pregnancy

The routine use of  diuretics in pregnancy is inappropriate and exposes the mother and fetus to unnecessary hazards. Edema occurs in a majority of pregnant women and is not harmful to either the mother or fetus. It can often be relieved by lying down or elevating the legs.

Diuretics, a group of drugs used to treat hypertension and edema, can cause harm by reducing the mother’s circulating blood volume. This reduces the amount of oxygen and nutrition available to the fetus. Diuretics can also cause low levels of sodium and potassium as well as yellow skin (jaundice) and bleeding in the newborn and have, in addition, the potential for some of the  adverse effects seen in the adult. Diuretics do not prevent the development of nor are they useful in the treatment of preeclampsia (toxemia of pregnancy). Thiazide diuretics can also cross the placenta and thus have the added potential for direct adverse effects.

Regardless of your age, reducing your blood pressure using diet and exercise, or diuretics if drug treatment is necessary, reduces your risk of heart attack and stroke.

When your blood pressure is taken, you are given two numbers, which represent the systolic pressure and the diastolic pressure—140/90 (mm Hg—millimeters of mercury, under pressure), for example. Systolic pressure, the upper number (140), reflects the pressure in the arteries as the heart contracts, pumps blood, and the blood vessels fill with blood. As the arteries harden with age (arteriosclerosis), the systolic pressure increases. Diastolic pressure, the lower number (90), reflects the pressure in the arteries as the heart relaxes and fills with blood. This is associated with a run-off of blood from the blood vessels.

A person’s blood pressure can be higher when measured at the doctor’s office than when measured at home; feeling nervous probably contributes to the higher reading. Ask your doctor about the various methods available for home monitoring of blood pressure, so you can see if yours is lower at home. If so, it is possible that you actually do not have high blood pressure and do not have to be treated.

Either your systolic or your diastolic pressure can be elevated. Elevations of either one or both of these pressures may significantly increase your chance of having a stroke or heart attack, much more so in the presence of other risk factors as discussed above.

Nondrug Treatment of High Blood Pressure

A healthy lifestyle is critical for the prevention of high blood pressure and is an essential part of the management of those with hypertension. Major lifestyle modifications shown to lower high blood pressure include weight reduction in those who are overweight or obese.[5],[6] In addition, sodium reduction and a diet rich in vegetables, fruits, and low-fat dairy products lowers blood pressure in both those with and without hypertension.[7],[8] For example, a 1,600 milligram sodium restriction has effects similar to treatment with a single blood-pressure-lowering drug.[9] Exercise[10] and moderate alcohol intake are also beneficial in maintaining a healthy blood pressure.[11]

A study of nutritional therapy showed that over one-third of people who previously needed drug treatment for high blood pressure were able to adequately control their blood pressure with nutritional therapy alone.[12] In addition, these methods are safer than using medication, since they have no adverse effects. Trying them will often make other beneficial contributions to your health.

  1. Lose weight: Nearly two-thirds of adults in the United States are overweight, and 30.5 percent are obese, according to data from a 1999–2000 National Institutes of Health survey. Many people in this category who lose weight can reduce their blood pressure by 15%.
  2. Reduce your salt intake: Changing your diet by not using your salt shaker and reducing your intake of processed and salty foods is a good first step.
  3. Restrict alcohol: Cutting alcohol intake to, at most, one drink a day also can reduce blood pressure.
  4. Exercise: Mild aerobic exercise such as walking 15 or 20 minutes a day at a comfortable pace will have a beneficial effect on heart and blood pressure.
  5. Decrease your fat intake: Decreasing the amount of animal fat in your diet has a beneficial effect on blood pressure. Furthermore, a high-fat diet is a risk factor for heart disease independent of high blood pressure. Decreasing the amount of fat in your diet will therefore help reduce your overall risk of developing heart disease.
  6. Increase the fiber in your diet: Diets with a high fiber content can lower blood pressure.[13] One study showed a drop of 10 mm Hg in systolic pressure and 5 mm Hg of diastolic pressure in people who took fiber supplements for two months, without any other dietary changes.[14] Fiber can be increased by eating more fruits, vegetables, and whole grains.

In a clinical trial performed on people 60 to 80 years old with well-controlled blood pressures, who had been taking a high-blood-pressure-lowering drug for years, found that keeping salt intake to 1,800 milligrams per day or less and losing a moderate amount of weight (on the order of 10 pounds) were responsible for further significant decreases in blood pressure while continuing drug treatment. At the end of the study more than 30% of the patients had lowered their blood pressure enough through salt reduction and weight loss to no longer require blood-pressure-lowering drugs. Salt reduction was equally effective in overweight and nonoverweight participants and was as effective as weight reduction in preventing recurrence of high blood pressure, need for a blood-pressure-lowering drug, or a cardiovascular event such as a stroke, heart attack, or chest pain (angina). Salt reduction combined with weight loss was more effective than either alone for control of high blood pressure, with or without the use of a blood-pressure-lowering drug.[15]

Decades of extensive research now make it possible to speak in terms of preventing high blood pressure rather than treating it with drugs, which is defensive, mainly reactive, time-consuming, associated with adverse drug effects, costly, only partially successful, endless, and is not a cure. In the editorial that accompanied the study the author said: “Hence, there is now evidence for a ‘fare for all seasons,’ to be consumed from post weaning through older age, to prevent adverse BP [blood pressure] levels, other major risk factors, and cardiovascular and other chronic diseases. This fare is delectably high in fruits and vegetables; high in legumes and whole grains; high in fat-free and low-fat dairy products, poultry, fish, shellfish, and meats; high in all essential nutrients; reduced in salt; reduced in total fat, saturated fat, and cholesterol; with no more than 2 drinks per day for those who choose to ingest alcohol; and controlled in calories to prevent or correct obesity.”[16]

When Is Drug Treatment Necessary?

Several factors should be taken into account when considering whether your high blood pressure should be treated. One is the benefits of the treatment for your blood pressure, which vary significantly depending on how high it is, your age, and whether you have other risk factors such as high cholesterol or are a smoker or a diabetic, and whether you have had a heart attack, heart failure, a stroke, or have kidney damage. The other consideration is the risks or the adverse effects of the treatment, which will vary depending on what is being considered.

Several studies have shown that the treatment of an elevated diastolic pressure does decrease your chance of having a stroke or heart attack. However, if only your systolic pressure is elevated, which often occurs in older adults, it is controversial as to what benefits are gained by treatment. Doctors generally agree that systolic blood pressure readings above a certain level—such as 160—are dangerous enough so that they require treatment. Treatment of systolic blood pressure below these levels is more controversial.

The following examples are applicable to people who do not have cardiovascular diseases such as a heart attack, angina, heart failure, or a stroke and who are between the ages of 30 and 74. The results are from an online cardiovascular risk calculator that can be found at www.widebaydgp.org.au/Resources/5yrRiskCalc.xls . [17]

Example A:  John is a 50-year-old man with a blood pressure of 160/90. With the upper limit of normal being 140/90, he has what is referred to as isolated systolic hypertension because of his systolic pressure of 160. However, John has a normal total cholesterol of 193 and a normal HDL (the “good” cholesterol) of 50. HDL is referred to as “good” cholesterol because it protects against coronary artery disease. He does not have diabetes, is not a smoker, has never had angina, a heart attack or heart failure, and does not have kidney damage. John turns out to have a 5-year risk of having a cardiovascular event (heart attack, stroke, etc.) of 6.2%, well under the 5-year risk of over 10% that might merit drug treatment.[2] It would be a good idea for John—or most people, for that matter—to adopt the nondrug approaches to lowering his blood pressure discussed above, but since his global risk is as low as it is, drug treatment is not indicated even if his blood pressure stays the same.

Example B:  Mary is a 60-year-old woman, also with a blood pressure of 160/90. Like John, Mary has a normal total cholesterol of 193 and a normal HDL (the “good” cholesterol) of 50. She also does not have diabetes, is not a smoker, and has never had angina, a heart attack, heart failure, or kidney damage. Using the same risk calculator, Mary’s 5-year risk of having a cardiovascular event is 6.8%, about the same as John’s even though she is 10 years older. Again, there is no reason for her to have drug treatment for her isolated systolic hypertension because her global risk is low.

There is little doubt that many Marys and Johns are being treated with drugs for high blood pressure even though their risk of strokes and heart attacks is as low as it is. This is because most doctors focus on just one risk factor—in this case blood pressure—instead of examining the total picture.

Example C:  Larry is a 50-year-old man who also has a blood pressure of 160/90, but he is a diabetic and although his total cholesterol is also 193, his HDL is only 40 (less of the “good cholesterol”). Though his blood pressure is the same as that of John and Mary, his 5-year cardiovascular risk is 17.6%, more than twice as high as theirs. He should start a program of exercise and diet to see if his blood pressure can be lowered that way, and then, if it still remains elevated, a drug to treat the hypertension such as a thiazide diuretic should be tried.

Are many people being given antihypertensive drugs unnecessarily? One study found that 41% of patients 50 and older who were carefully taken off their high blood pressure medications did not need them, having normal blood pressure 11 months after the drug was stopped.[18]

Which Drug to Use?

Regardless of your age, much of the time high blood pressure can be controlled with just one drug. The National Institutes of Health’s National Heart, Lung and Blood Institute recommends beginning treatment with a mild water pill (diuretic) at a low dose. The safest and best studied of the diuretics is hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE). The starting dose should be low: 12.5 to 25 milligrams per day or even every other day. Confirming the advice we have been giving since 1988 is a large definitive study (named ALLHAT) involving more than 33,000 patients aged 55 or older that found “compelling evidence that thiazide diuretics (such as hydrochlorothiazide or chlorthalidone) should be the initial drug of choice for patients with hypertension.” Thus, the widespread prescribing practice—spurred on by massive advertising—of starting people with newly diagnosed hypertension with calcium channel blockers (such as Norvasc, Cardizem, or Procardia), ACE inhibitors (such as Zestril, Accupril, or Vasotec), or other drugs that are not thiazides lacks any scientific rationale.

For older adults, in general, the rule for treating high blood pressure, as with so many other drug treatments, is “start low and go slow.” According to experts in prescribing for older adults, for mild hypertension (or heart failure) start with half the standard starting dose and increase gradually.

If a second drug is needed ACE inhibitors are effective drugs to use as a second agent. It is rarely necessary to take more than two drugs to treat high blood pressure. If you are taking more than two, a reassessment is indicated.

Common Adverse Effects of High Blood Pressure Drugs

The decision to use drugs to treat high blood pressure should be based on a consideration of both the benefits and the risks of the treatment. Therefore it is very important that you report any adverse effects of the drugs to your doctor, so that your situation can be reassessed. These are some of the possible adverse effects of the various antihypertensive drugs.[19]

  • Depression—especially with beta-blockers, reserpine, methyldopa, and clonidine. (See drugs that can cause depression.)
  • Sedation and fatigue—especially with beta-blockers, reserpine, methyldopa, and clonidine.
  • Impotence and sexual dysfunction—especially with beta-blockers, methyldopa, and many other heart drugs. (See drugs that can cause sexual dysfunction.)
  • Dizziness (from a drop in blood pressure after standing up, which can result in accidental falls and broken bones)—seen with all high blood pressure drugs to some degree, and especially with guanethidine, prazosin, and methyldopa. Older adults are more prone to this adverse effect because the internal blood pressure regulation system works more slowly as we age. (See drugs that can cause dizziness on standing.)
  • Loss of appetite and nausea—especially with hydrochlorothiazide, digoxin, and potassium supplements. (See drugs that can cause loss of appetite, nausea, or vomiting.)

These and other adverse effects can occur with any medication for high blood pressure. Those listed occur most often. If you experience any effects, or just feel worse in general, tell your doctor. It is often better to tolerate a slightly higher blood pressure with no adverse effects from medication than to have a lower blood pressure along with serious effects from medication that will adversely affect your life.

For example, let’s consider the steps in devising a treatment for a 75-year-old woman whose baseline blood pressure is 200/90 mm Hg:

  1. She is first treated with 12.5 milligrams of hydrochlorothiazide. This results in a blood pressure of 170/90, and she feels quite well.
  2. Her doctor attempts to lower her blood pressure further by adding another drug, propranolol, to her treatment. This results in a blood pressure of 160/90, but she “feels awful” and complains of fatigue and confusion.
  3. Her doctor might consider discontinuing the propranolol and using another drug. A better idea might be to accept a blood pressure of 170/90 using hydrochlorothiazide alone or to lower it further with nondrug therapy.

Stopping Drug Treatment

Historically, patients have been taught that hypertension means treatment for life, although countless thousands of patients have abandoned their treatment without their doctors’ knowledge or consent. For some patients, this may be a dangerous idea, but for many others the treatment may no longer be needed. Two large studies in Australia and Britain have shown that one-third to one-half of patients with mild hypertension for whom treatment was stopped had normal blood pressures a year or more later.[20]

An editorial in the British Medical Journal stated, “Treatment of hypertension is part of preventive medicine and like all preventive strategies, its progress should be regularly reviewed by whoever initiates it. Many problems could be avoided by not starting antihypertensive treatment until after prolonged observation....Patients should no longer be told that treatment is necessarily for life: the possibility of reducing or stopping treatment should be mentioned at the outset.”[20]

This view is shared by American experts in hypertension who have stated that “once blood pressure has been normal for a year or more, a cautious decrease in antihypertensive dosage and renewed attention to nonpharmacologic treatment may be worth trying.”[21]

Drugs Used to Treat High Blood Pressure

Diuretics

Eighteen different diuretics are available in the U.S., falling into three general categories: (1) the thiazide type, the best-known member of which is  hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE); (2) loop diuretics, which include furosemide (LASIX) (the “loop” pertains to the part of the kidney in which the drug works) and are more potent than the thiazide type for removing sodium and fluid, but are not first-choice drugs for the treatment of high blood pressure; and (3) potassium-sparing diuretics, which, as the name implies, cut down on the loss of potassium in the minority of patients whose blood levels of potassium decrease when taking thiazides or loop diuretics.

The latest revision of the National Institutes of Health’s guidelines on high blood pressure, the Seventh Report of the Joint National Committee, or JNC VII, again recommends that thiazide diuretics should be used in the drug treatment for most patients with uncomplicated high blood pressure, either alone or in combination with other drugs.[22]

The thiazide-type diuretics improve survival in patients with high blood pressure. They also have been shown to reduce incidence of stroke and cardiovascular events in elderly people with a type of high blood pressure known as isolated systolic hypertension. The most widely used thiazide diuretics are hydrochlorothiazide and chlorthalidone (HYGROTON).

We have long recommended, as does JNC VII, that the starting dose of hydrochlorothiazide should be 12.5 milligrams per day. For years the lowest strength available was a 25 milligram tablet that had to be broken in half to achieve the 12.5 milligram dose. There is now a 12.5 milligram capsule of hydrochlorothiazide available with the brand name Microzide.

There is growing evidence that thiazide diuretics, such as hydrochlorothiazide, significantly decrease the rate of bone mineral loss in both men and women because they reduce the amount of calcium lost in the urine. Research now suggests that thiazide diuretics may protect against hip fracture.

The loop diuretics can be used to treat high blood pressure in patients with kidney insufficiency. In those without kidney insufficiency, they may be less effective than the thiazides for the treatment of high blood pressure.

The potassium-sparing diuretics can cause dangerously elevated blood levels of potassium, particularly in patients with kidney impairment and in those taking ACE inhibitors, angiotensin receptor blockers (ARBs), or using potassium supplements.

 

Diuretics
Generic Drug Name (BRAND NAME)
Thiazide Type
bendroflumethiazide (NATURETIN)
chlorothiazide (DIURIL)
hydrochlorothiazide (ESIDREX, MICROZIDE)
hydroflumethiazide (SALURON, DIUCARDIN)
chlorthalidone (HYGROTON)
indapamide (LOZOL)
methyclothiazide (ENDURON)
metolazone (ZAROXOLYN, MYKROX)
polythiazide (RENESE)
trichlormethiazide (NAQUA)
Loop Type
bumetanide (BUMEX)
ethacrynic acid (EDECRIN)
furosemide (LASIX)
torsemide (DEMADEX)
Potassium-Sparing
amiloride (MIDAMOR)
eplerenone (INSPIRA)
spironolactone (ALDACTONE)
triamterene (DYRENIUM)

Beta-blockers

Currently, there are 13 beta-blockers on the U.S. market. In addition to high blood pressure, some of the beta-blockers are also used to treat chest pain (angina), heart attacks, irregular heart rhythms, glaucoma, and migraine headaches.

Beta-blockers should not be taken if you have asthma, emphysema, chronic bronchitis, bronchospasm, allergies, or heart block. If you have heart failure, beta-blockers can cause dramatic improvement but must be taken under careful supervision. A baseline electrocardiogram (ECG, EKG) should be taken before a beta-blocker is first prescribed to be sure that you do not have heart block. Do not smoke while taking a beta-blocker (you shouldn’t be smoking anyway). If you smoke, you might as well stop taking the beta-blocker. Not only will smoking aggravate some of the respiratory adverse effects, but it greatly reduces the level of drug in your body.

Beta-blockers can cause a spasm in the air passages of the lungs (bronchospasm) and bring on asthmatic wheezing even when beta-blocker eye drops are used to treat glaucoma. Therefore, beta-blockers should not be used if you have asthma, bronchospasm, chronic bronchitis, or emphysema. If you are experiencing breathing difficulty while taking a beta-blocker, call your doctor immediately.

The following table lists the beta-blockers currently available on the U.S. market.

 

Beta-blockers
Generic Drug Name (BRAND NAME)

acebutolol (SECTRAL)
atenolol (TENORMIN)
betaxolol (KERLONE)
bisoprolol (ZEBETA)
carteolol (CARTROL)
carvedilol (COREG)
labetalol (NORMODYNE, TRANDATE)
metoprolol (LOPRESSOR, TOPROL XL)
nadolol (CORGARD)
penbutolol (LEVATOL)
pindolol (VISKEN)
propranolol (INDERAL)
timolol (BLOCADREN)

Alpha-blockers

This family of drugs includes doxazosin (CARDURA), prazosin (MINIPRESS), and terazosin (HYTRIN). The alpha-blockers are also used to treat benign prostatic hyperplasia, or an enlarged prostate gland.

The National Institutes of Health (NIH) no longer recommends the routine use of alpha-blockers for the treatment of high blood pressure.[22]

In March 2000, the NIH announced that it had stopped one part of a large high blood pressure study because the alpha-blocker doxazosin proved to be less effective than the old thiazide diuretic chlorthalidone (HYGROTON) in reducing some forms of cardiovascular disease. The study, called the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), found users of doxazosin had 25% more cardiovascular events and were twice as likely to be hospitalized for congestive heart failure as users of chlorthalidone.[23]

Angiotensin Converting Enzyme (ACE) Inhibitors

There are now 10 angiotensin converting enzyme (ACE) inhibitors on the U.S. market. The ACE inhibitors work to lower blood pressure by preventing the production of angiotensin II, a potent, naturally occurring hormone that raises blood pressure.

The two most-studied ACE inhibitors, captopril (CAPOTEN) and enalapril (VASOTEC), are available at lower cost as generics.

All ACE inhibitors reduce blood pressure and various ACE inhibitors reduce mortality in patients with coronary artery disease. They prolong the survival of patients with heart failure after a heart attack, and preserve kidney function in those with diabetes. The ACE inhibitors may also preserve kidney function in nondiabetic patients with a kidney disorder.[24] The table below lists the available ACE inhibitors and their FDA-approved uses.

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. You should always tell your doctor if you are pregnant or thinking of becoming pregnant before you use an ACE inhibitor.

A common adverse effect, after taking ACE inhibitors for a few weeks, is a dry, hacking cough, especially in women. Check with your doctor about a four-day withdrawal from your ACE inhibitor to determine if this is the cause of your cough. This trial withdrawal can prevent unnecessary and sometimes costly tests and treatments to determine other causes of cough.

 

FDA-approved uses for ACE inhibitors
Generic Drug Name (BRAND NAME) High Blood Pressure Heart Failure Left Ventrical Dysfunction after Heart Attack Asymptomatic Left Ventricular Dysfunction Acute Heart Attack Risk Reduction of Heart Attack, Stroke, Cardiovascular Death
benazepril (LOTENSIN) yes          
captopril (CAPOTEN) yes yes yes      
enalapril (VASOTEC) yes yes   yes    
fosinopril (MONOPRIL) yes yes        
lisinopril (PRINIVIL, ZESTRIL) yes yes     yes  
moexipril (UNIVASC) yes          
perindopril (ACEON) yes          
quinapril (ACCUPRIL) yes yes        
ramipril (ALTACE) yes yes       yes
trandolapril (MAVIK) yes yes yes      

 

Angiotensin Receptor Blockers (ARBs)

Seven ARBs are now on the market in the United States. These drugs work by blocking the effect of angiotensin II, a potent, naturally occurring hormone that raises blood pressure. In contrast, the previously mentioned ACE inhibitors prevent the production of angiotensin II in the body.

The best therapeutic role for the ARBs appears to be in patients in whom ACE inhibitors are indicated but who are unable to tolerate them.

The development of the dry, hacking cough often seen with the use of ACE inhibitors does not appear to be as frequent with the angiotensin receptor antagonists. This family of drugs carries the same warning as ACE inhibitors about use in pregnancy.

The table below lists the available ARBs and their FDA-approved uses.

 

FDA-approved uses for angiotensin receptor blockers
Generic Drug Name (Brand) High Blood Pressure Reduce the Risk of Stroke Prevent Kidney Damage in Diabetics with High Blood Pressure Heart Failure in Those That Can’t Take ACE Inhibitors
candesartan (ATACAND) yes      
eprosartan (TEVETEN) yes      
irbesartan (AVAPRO) yes      
losartan (COZAAR) yes yes yes  
olmesartan (BENICAR) yes      
telmisartan (MICARDIS) yes      
valsartan (DIOVAN) yes     yes

Calcium Channel Blockers

There are currently eight calcium channel blockers on the market in the United States. Despite recommendations of the National Institutes of Health’s National Heart, Lung and Blood Institute dating back to 1993 that diuretics should be used first in the treatment of mild to moderate high blood pressure, the calcium channel blockers remained the largest-selling family of high-blood-pressure-lowering drugs in the United States during the 1990s.[25] In 2002, the calcium channel blocker amlodipine (NORVASC) was the fourth most frequently dispensed drug in the United States, with over 30 million prescriptions being dispensed.

The calcium channel blocker mibefradil (POSICOR) was withdrawn from the market because of harmful drug interactions.

In 1995, Public Citizen’s Health Research Group filed a petition with the Food and Drug Administration to add warnings to the labeling of all calcium channel blockers about the increased risk of heart attack and death. Our petition was based on three well-conducted observational research studies.[26],[27],[28]

Observational studies are frequently criticized by doctors who do not understand this type of research. Most of what we know about adverse drug reactions and what we are likely to learn in the future about them comes from observational research. This type of research was used to show the link between cigarette smoking and lung cancer.

Our petition helped to bring about important labeling changes in February 1996 on one of the calcium channel blockers, the short-acting form of nifedipine. The labeling for this form of nifedipine now warns doctors that this product should not be used for the treatment of high blood pressure because of sudden, life-threatening decreases in blood pressure that can occur.

The calcium channel blockers currently marketed in the United States are listed in the following table.

Calcium channel blockers
amlodipine (NORVASC)
diltiazem (CARDIZEM, CARDIZEM CD)
felodipine (PLENDIL)
isradipine (DYNACIRC)
nicardipine (CARDENE)
nifedipine (PROCARDIA XL)
nisoldipine (SULAR)
verapamil (COVERA HS)