What does the research show about calcium channel blockers?

Calcium channel blockers

Trials found calcium channel blockers lowered blood pressure and stroke, with more heart failure than diuretics or ACE inhibitors. Amlodipine lowered angina hospitalizations. Ankle swelling is the most frequent side effect, 10.7% against 3.2% on controls. Diltiazem and verapamil slow the heart rate and raise blood levels of some statins.

Add to Bio HackChecked 2026-11-13

Status: Prescription drugs in the US. Amlodipine is FDA-approved for high blood pressure and coronary artery disease, including angina. Extended-release diltiazem is approved for high blood pressure and angina, and extended-release verapamil for high blood pressure. Approved uses differ by drug and formulation. The class has two subgroups: dihydropyridines (amlodipine, nifedipine) and non-dihydropyridines (diltiazem, verapamil).
Also called: amlodipine, Norvasc, Katerzia, nifedipine, Procardia XL, Adalat CC, felodipine, diltiazem, Cardizem, Cartia XT, Tiazac, verapamil, Calan, Verelan, dihydropyridine, non-dihydropyridine, calcium antagonist, CCB
Taken for: high blood pressure, angina and chest pain, stroke prevention, heart rate control in atrial fibrillation, Raynaud's attacks, cluster headache prevention, delaying preterm labor

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help7

ModerateShown to lower blood pressure by about 9/5.5 mm Hg at standard dose, similar to the other main classes of blood pressure drug.
ModerateShown to lower stroke from 3.4% to 1.9% and total cardiovascular events from 8.0% to 5.7% against placebo, with no significant change in deaths.
ModerateShown to lower hospital stays for angina and artery procedures in coronary disease, with no change in deaths. The trials tested amlodipine and nifedipine.
ModerateShown to lower Raynaud's attacks by about 3 to 6 a week against placebo, with a small drop in attack severity.
LimitedOne small crossover trial found diltiazem and verapamil lowered 24-hour heart rate in permanent atrial fibrillation, from 96 beats a minute to 75 and 81.
LimitedOne small trial found verapamil lowered attack frequency in episodic cluster headache against placebo over 14 days.
LimitedSmall trials found calcium channel blockers, mainly nifedipine, lowered birth within 48 hours in preterm labor against placebo or no treatment.

Reported risks14

ModerateShown to raise ankle and leg swelling, 10.7% against 3.2% on controls, more often on dihydropyridines and at higher doses.Very common
ModerateShown to raise flushing and palpitations with dose on amlodipine, with palpitations in 4.5% at 10 mg against 0.6% on placebo.Common
ModerateShown to slow the heart on diltiazem, with a slow heart rate in 3.3% against 1.3% on placebo. The same is reported for verapamil.Common
ModerateShown to cause constipation on verapamil, reported by 7.3% of people in its trials. The label gives no placebo rate.Common
ModerateShown to bring more heart failure than diuretics or ACE inhibitors in blood pressure trials. Verapamil and diltiazem labels warn of worsening in a weakened heart.Common
LimitedOne study found significant gum overgrowth in 6.3% of people on nifedipine, more than in controls. Amlodipine and diltiazem did not differ from controls.Common
LimitedLinked to more hospital stays for acute kidney injury in older adults given clarithromycin while on a calcium channel blocker, 0.44% against 0.22% with azithromycin.Uncommon
LimitedMixed results: one case-control study linked 10 or more years of use to breast cancer, and a pooled analysis and a larger cohort found no link.Uncommon
ModerateShown to raise deaths in people with coronary disease at nifedipine doses of 80 mg a day in 16 older trials. A later long-acting nifedipine trial found no rise.How often is not known
LimitedSmall studies found diltiazem, verapamil and amlodipine raise blood levels of simvastatin, about 5-fold with diltiazem. Labels warn of a higher risk of muscle injury.How often is not known
LimitedThe label warns that verapamil or diltiazem with a beta-blocker can add to slowing of the heart, and that verapamil raises digoxin levels 50 to 75%.How often is not known
LimitedThe label warns that amlodipine may raise blood levels of cyclosporine and tacrolimus, and that blood pressure may fall further with sildenafil.How often is not known
LimitedOne small study found grapefruit juice raised felodipine blood levels to 284% of those with water, with lower diastolic pressure and a higher heart rate.How often is not known
LimitedThe label states that data on amlodipine in pregnancy are too limited to estimate a risk of birth defects or miscarriage.How often is not known

What people take it for, and what was found

Shown to help7

Moderate

Lowering blood pressure

Shown to lower blood pressure by about 9/5.5 mm Hg at standard dose, similar to the other main classes of blood pressure drug.

The numbers and sources

Effect: Across 354 placebo-controlled trials, calcium channel blockers lowered blood pressure by about the same amount as thiazides, beta-blockers, ACE inhibitors and ARBs, on average 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1/4.4 mm Hg at half dose. Symptoms attributed to calcium channel blockers rose with dose [1]. In older adults with isolated systolic hypertension, treatment starting with the dihydropyridine nitrendipine lowered blood pressure by 10.1/4.5 mm Hg more than placebo at 2 years [2].
Population: About 40,000 treated and 16,000 placebo participants in 354 trials of five drug classes [1]; 4,695 adults over 60 with systolic pressure of 160 to 219 mm Hg [2].
Sources: [1], [2]
Caveats: The pooled analysis reports the class as a whole and does not separate the two subgroups [1]. The trial is of a dihydropyridine, with enalapril and hydrochlorothiazide added as needed [2].

Moderate

Stroke and heart events against placebo

Shown to lower stroke from 3.4% to 1.9% and total cardiovascular events from 8.0% to 5.7% against placebo, with no significant change in deaths.

The numbers and sources

Effect: A Cochrane review found first-line calcium channel blockers lowered stroke (3.4% with control against 1.9%, RR 0.58, 95% CI 0.41 to 0.84) and total cardiovascular events (8.0% against 5.7%, RR 0.71, 95% CI 0.57 to 0.87). Coronary heart disease (RR 0.77, 95% CI 0.55 to 1.09) and mortality (RR 0.86, 95% CI 0.68 to 1.09) did not differ significantly [3]. In the Syst-Eur trial of nitrendipine-based treatment, stroke fell from 13.7 to 7.9 events per 1,000 patient-years (42% reduction) and all cardiovascular endpoints fell 31%, with no significant change in all-cause mortality [2].
Population: Adults with moderate to severe primary hypertension, mean age 56, within a review of 24 trials and 58,040 people across drug classes [3]; 4,695 adults over 60 with isolated systolic hypertension, median 2 years [2].
Sources: [3], [2]
Caveats: The Cochrane authors rated this evidence low quality [3]. The trial evidence is for a dihydropyridine [2].

Moderate

Angina and coronary artery disease

Shown to lower hospital stays for angina and artery procedures in coronary disease, with no change in deaths. The trials tested amlodipine and nifedipine.

The numbers and sources

Effect: In CAMELOT, a first cardiovascular event occurred in 16.6% on amlodipine and 23.1% on placebo over a mean 19 months (HR 0.691, 95% CI 0.540 to 0.884), mostly through fewer hospitalizations for angina and fewer revascularization procedures [8]. In ACTION, long-acting nifedipine did not change the main composite of death, heart attack, refractory angina, heart failure, stroke and peripheral revascularization (4.60 against 4.75 per 100 patient-years, HR 0.97, 95% CI 0.88 to 1.07) or deaths (HR 1.07, 95% CI 0.91 to 1.25). Death or any cardiovascular event or procedure was less frequent (9.32 against 10.50 per 100 patient-years, HR 0.89), mainly from less coronary angiography and intervention [9].
Population: 1,318 people with coronary artery disease on angiography assigned to amlodipine 5 to 10 mg or placebo [8]; 7,665 people with treated stable angina, mean 4.9 years [9].
Sources: [8], [9]
Caveats: Both drugs are dihydropyridines. The diltiazem label also lists angina as an approved use, and its trial data were not sourced for this block [10].

Limited

Heart rate control in atrial fibrillation

One small crossover trial found diltiazem and verapamil lowered 24-hour heart rate in permanent atrial fibrillation, from 96 beats a minute to 75 and 81.

The numbers and sources

Effect: Mean 24-hour heart rate was 96 beats a minute untreated, 75 on diltiazem 360 mg a day, 81 on verapamil 240 mg a day, 82 on metoprolol 100 mg a day and 84 on carvedilol 25 mg a day. All four drugs lowered heart rate against baseline [11].
Population: 60 adults with permanent atrial fibrillation, mean age 71, given each drug for 3 weeks in random order [11].
Sources: [11]
Caveats: One small investigator-blind trial of 3-week periods. The evidence is for the non-dihydropyridines only.

Moderate

Raynaud's attacks

Shown to lower Raynaud's attacks by about 3 to 6 a week against placebo, with a small drop in attack severity.

The numbers and sources

Effect: In 23 trials, calcium channel blockers lowered attacks by about 6 a week (WMD -6.13, 95% CI -6.60 to -5.67) from 13.7 a week on placebo, with very high heterogeneity (I² 98%). With one outlying trial removed, the reduction was 2.93 a week (95% CI -3.44 to -2.43). Attack severity fell by 0.62 cm on a 10 cm scale in 16 trials, and attack duration did not differ significantly [12].
Population: 528 people with primary or secondary Raynaud's phenomenon in 23 trials, within a review of 38 trials and 982 participants averaging 7.4 weeks [12].
Sources: [12]
Caveats: Moderate quality evidence, downgraded for inconsistency. Most trials were small crossover studies. The abstract does not break results out by drug subgroup [12].

Limited

Cluster headache prevention

One small trial found verapamil lowered attack frequency in episodic cluster headache against placebo over 14 days.

The numbers and sources

Effect: Over 14 days, the verapamil group had a significant reduction in attack frequency and in use of medication to stop attacks, against placebo [13].
Population: 30 people with episodic cluster headache, 15 on verapamil 120 mg three times a day and 15 on placebo [13].
Sources: [13]
Caveats: One small trial, and the abstract gives no effect size. The evidence is for verapamil, a non-dihydropyridine. Not an FDA-approved use.

LimitedStudied in pregnancy

Delaying preterm birth

Small trials found calcium channel blockers, mainly nifedipine, lowered birth within 48 hours in preterm labor against placebo or no treatment.

The numbers and sources

Effect: In 2 small trials against placebo or no treatment, birth within 48 hours of entry was less frequent (RR 0.30, 95% CI 0.21 to 0.43). The two trials disagreed on birth before 37 weeks. Against other drugs used to delay labor, there was no significant reduction in birth within 48 hours or in perinatal mortality, and there were fewer maternal adverse effects than with betamimetics (RR 0.36, 95% CI 0.24 to 0.53) [14].
Population: 3,550 women in 38 trials, 35 of which used nifedipine [14].
Sources: [14]
Caveats: Only one trial was placebo controlled and blinded. The evidence is for nifedipine, a dihydropyridine. Not an FDA-approved use.

Mixed results1

Moderate

Compared with other blood pressure drugs

Mixed results: fewer strokes than beta-blockers or ACE inhibitors, more heart failure than diuretics or ACE inhibitors, and no difference in deaths from any cause.

The numbers and sources

Effect: In 23 trials of first-line treatment, all-cause mortality did not differ between calcium channel blockers and any other class. Against diuretics, heart failure was more frequent (RR 1.37, 95% CI 1.25 to 1.51). Against beta-blockers, major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92) and stroke (RR 0.77, 95% CI 0.67 to 0.88) were less frequent. Against ACE inhibitors, stroke was less frequent (RR 0.90, 95% CI 0.81 to 0.99) and heart failure more frequent (RR 1.16, 95% CI 1.06 to 1.28) [4]. In ALLHAT, amlodipine did not differ from chlorthalidone on fatal coronary disease or nonfatal heart attack (RR 0.98, 95% CI 0.90 to 1.07) and had a higher 6-year rate of heart failure (10.2% against 7.7%) [5]. An amlodipine-based regimen brought fewer strokes than an atenolol-based one (HR 0.77, 95% CI 0.66 to 0.89) [6]. Benazepril plus amlodipine brought fewer cardiovascular events than benazepril plus hydrochlorothiazide (9.6% against 11.8%, HR 0.80) [7].
Population: 153,849 people with hypertension in 23 trials, 18 of dihydropyridines and 4 of non-dihydropyridines [4]; 33,357 adults aged 55 or older in ALLHAT, mean 4.9 years [5]; 19,257 adults with hypertension and three other risk factors [6]; 11,506 high-risk adults with hypertension [7].
Sources: [4], [5], [6], [7]
Caveats: Most of the evidence is for dihydropyridines, and the three named trials all used amlodipine. Certainty was rated low to moderate across comparisons [4].

Doses studied

The amlodipine label reports placebo-controlled trials of 2.5, 5 and 10 mg once daily, and CAMELOT used 5 to 10 mg [8]. ALLHAT used amlodipine 2.5 to 10 mg a day [5]. ACTION used nifedipine in a long-acting form at 60 mg once daily [9], and Syst-Eur used nitrendipine 10 to 40 mg a day [2].

The diltiazem label reports placebo-controlled trials of the extended-release capsule at up to 360 mg a day and a dose-response study of 60 to 480 mg once daily [10]. The atrial fibrillation trial used diltiazem 360 mg and verapamil 240 mg a day [11], and the cluster headache trial used verapamil 120 mg three times a day [13].

Risks

Reported risks12

ModerateVery common

Ankle and leg swelling

Shown to raise ankle and leg swelling, 10.7% against 3.2% on controls, more often on dihydropyridines and at higher doses.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: Across 106 trials in hypertension, peripheral edema occurred in 10.7% on calcium channel blockers and 3.2% on control or placebo, and 2.1% against 0.5% stopped treatment over it. It was more frequent on dihydropyridines (12.3%) than non-dihydropyridines (3.1%), and at high doses (16.1%) than low doses (5.7%), and reached 24% after 6 months [15]. In placebo-controlled trials of amlodipine, edema occurred in 1.8%, 3.0% and 10.8% at 2.5, 5 and 10 mg, against 0.6% on placebo [8]. On extended-release diltiazem, edema occurred in 2.6% against 1.3% on placebo [10].
Population: 99,469 people in 106 trials, mean age 56 [15]; 839 people on amlodipine and 520 on placebo [8]; 607 people on diltiazem and 301 on placebo [10].
Sources: [15], [8], [10]
Caveats: Trials of at least 100 people on a calcium channel blocker and at least 4 weeks [15].

ModerateCommon

Dizziness, flushing and palpitations

Shown to raise flushing and palpitations with dose on amlodipine, with palpitations in 4.5% at 10 mg against 0.6% on placebo.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In placebo-controlled trials of amlodipine at 2.5, 5 and 10 mg, dizziness occurred in 1.1%, 3.4% and 3.4% against 1.5% on placebo, flushing in 0.7%, 1.4% and 2.6% against 0.0%, and palpitations in 0.7%, 1.4% and 4.5% against 0.6%. Fatigue occurred in 4.5% against 2.8%. The label states that symptomatic low blood pressure is possible, and that worsening angina or a heart attack can develop after starting or raising the dose, particularly in severe obstructive coronary disease [8].
Population: 839 people on amlodipine and 520 on placebo in dose-ranging trials, and 1,730 against 1,250 for fatigue [8].
Sources: [8]
Caveats: The evidence is for amlodipine, a dihydropyridine.

ModerateCommon

Slow heart rate and heart block

Shown to slow the heart on diltiazem, with a slow heart rate in 3.3% against 1.3% on placebo. The same is reported for verapamil.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In placebo-controlled trials of extended-release diltiazem, a slow heart rate occurred in 3.3% against 1.3% on placebo and first-degree heart block in 3.3% against 0.0%. Second- or third-degree heart block occurred in 13 of 3,290 people (0.40%) [10]. In trials of oral verapamil, a heart rate below 50 a minute occurred in 1.4% and heart block of any degree in 1.2%, with no placebo rate given [16].
Population: 607 people on diltiazem and 301 on placebo, and 3,290 people for higher-degree block [10]; 4,954 people on verapamil [16].
Sources: [10], [16]
Caveats: The evidence is for the non-dihydropyridines. People with conduction abnormalities were usually excluded from these trials [10].

ModerateCommon

Constipation

Shown to cause constipation on verapamil, reported by 7.3% of people in its trials. The label gives no placebo rate.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: In clinical trials of oral verapamil, constipation was the most frequent reaction, in 7.3%, followed by dizziness (3.3%), nausea (2.7%) and low blood pressure (2.5%). The label also notes infrequent reports of reversible paralytic ileus [16].
Population: 4,954 people in clinical trials of oral verapamil [16].
Sources: [16]
Caveats: The evidence is for verapamil, a non-dihydropyridine. No placebo rate is given.

ModerateCommon

Heart failure

Shown to bring more heart failure than diuretics or ACE inhibitors in blood pressure trials. Verapamil and diltiazem labels warn of worsening in a weakened heart.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: As first-line blood pressure treatment, calcium channel blockers brought more heart failure than diuretics (RR 1.37, 95% CI 1.25 to 1.51) and ACE inhibitors (RR 1.16, 95% CI 1.06 to 1.28) [4]. In ALLHAT the 6-year rate was 10.2% on amlodipine and 7.7% on chlorthalidone (RR 1.38, 95% CI 1.25 to 1.52) [5]. In clinical trials of verapamil, 1.8% developed heart failure or pulmonary edema [16]. After a heart attack, diltiazem was associated with more cardiac events in people with lung congestion (HR 1.41) and fewer in those without (HR 0.77, 95% CI 0.61 to 0.98) [17]. The diltiazem label reports worsening heart failure in people with impaired ventricular function [10].
Population: 153,849 people in 23 trials [4]; 24,303 people assigned to amlodipine or chlorthalidone [5]; 4,954 people on verapamil [16]; 2,466 people after a heart attack, 490 with lung congestion [17].
Sources: [4], [5], [16], [17], [10]
Caveats: The blood pressure trials compare drugs with each other, not with placebo. The band is taken from the verapamil trials. In severe heart failure, amlodipine did not raise deaths against placebo [18].

LimitedCommon

Gum overgrowth

One study found significant gum overgrowth in 6.3% of people on nifedipine, more than in controls. Amlodipine and diltiazem did not differ from controls.

The numbers and sources

How common: Common: between 1 in 100 and 1 in 10 people.
Effect: Significant gingival overgrowth was seen in 6.3% of people taking nifedipine, more than in the amlodipine, diltiazem or control groups. Its prevalence on amlodipine or diltiazem did not differ significantly from controls [19].
Population: 442 people on nifedipine, 181 on amlodipine, 186 on diltiazem and 102 controls from general practices in northeast England [19].
Sources: [19]
Caveats: One cross-sectional community study. The abstract does not give the rate in controls.

LimitedUncommon

With clarithromycin

Linked to more hospital stays for acute kidney injury in older adults given clarithromycin while on a calcium channel blocker, 0.44% against 0.22% with azithromycin.

The numbers and sources

How common: Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect: Within 30 days of a new prescription, hospitalization with acute kidney injury occurred in 0.44% of those given clarithromycin and 0.22% of those given azithromycin. The risk was highest with nifedipine (OR 5.33, 95% CI 3.39 to 8.38). Hospitalization with low blood pressure (0.12% against 0.07%, OR 1.60) and death from any cause (1.02% against 0.59%, OR 1.74, 95% CI 1.57 to 1.93) were also more frequent [21].
Population: Ontario adults with a mean age of 76 on amlodipine, felodipine, nifedipine, diltiazem or verapamil, 96,226 given clarithromycin and 94,083 given azithromycin [21].
Sources: [21]
Caveats: Observational, in older adults. More than half were on amlodipine.

ModerateHow often is not known

Nifedipine and deaths in coronary disease

Shown to raise deaths in people with coronary disease at nifedipine doses of 80 mg a day in 16 older trials. A later long-acting nifedipine trial found no rise.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 16 randomized secondary-prevention trials of nifedipine in people with coronary heart disease, total mortality was higher on nifedipine (RR 1.16, 95% CI 1.01 to 1.33). The risk rose with dose: 1.06 at 30 to 50 mg a day, 1.18 at 60 mg and 2.83 (95% CI 1.35 to 5.93) at 80 mg [20]. In a later trial of long-acting nifedipine in stable angina, deaths did not differ from placebo (HR 1.07, 95% CI 0.91 to 1.25) [9].
Population: People with coronary heart disease in 16 secondary-prevention trials [20]; 7,665 people with stable angina [9].
Sources: [20], [9]
Caveats: The pooled trials were published before 1995, and the abstract does not name the formulations or give absolute death rates [20].

LimitedHow often is not known

With simvastatin and other statins

Small studies found diltiazem, verapamil and amlodipine raise blood levels of simvastatin, about 5-fold with diltiazem. Labels warn of a higher risk of muscle injury.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 10 healthy volunteers, diltiazem raised simvastatin exposure 5-fold, and in another 10 it raised lovastatin exposure 3 to 4-fold and left pravastatin unchanged. The diltiazem label states that the risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased [10]. The verapamil label reports simvastatin exposure 2.5 times that of simvastatin alone and sets dose limits of 10 mg for simvastatin and 40 mg for lovastatin [16]. The amlodipine label states that it increases simvastatin exposure and sets a limit of 20 mg of simvastatin a day [8].
Population: Healthy volunteers in small crossover studies described in the labels [10][16][8].
Sources: [10], [16], [8]
Caveats: The studies measured blood levels, not muscle injury. No rate of muscle injury is given.

LimitedHow often is not known

With beta-blockers or digoxin

The label warns that verapamil or diltiazem with a beta-blocker can add to slowing of the heart, and that verapamil raises digoxin levels 50 to 75%.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The verapamil label states that use with beta-blockers may have additive negative effects on heart rate, conduction and contractility, and that excessive slowing of the heart and heart block have been reported. It states that long-term verapamil can raise serum digoxin by 50 to 75% in the first week, which can result in digitalis toxicity [16]. The diltiazem label describes additive effects on conduction with beta-blockers or digitalis, and a rise of about 20% in digoxin levels in one study of 24 healthy men [10].
Population: People taking verapamil or diltiazem with a beta-blocker or digoxin, as described in the labels, and 24 healthy men in one digoxin study [16][10].
Sources: [16], [10]
Caveats: The labels give no rate. The warning is for the non-dihydropyridines.

LimitedHow often is not known

With cyclosporine, tacrolimus or sildenafil

The label warns that amlodipine may raise blood levels of cyclosporine and tacrolimus, and that blood pressure may fall further with sildenafil.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The amlodipine label states that it may increase systemic exposure to cyclosporine or tacrolimus, and calls for monitoring for low blood pressure when sildenafil is taken with it. It also states that moderate and strong CYP3A inhibitors increase exposure to amlodipine [8].
Population: People taking amlodipine with these drugs, as described in the label [8].
Sources: [8]
Caveats: The label gives no rate.

LimitedStudied in menHow often is not known

With grapefruit juice

One small study found grapefruit juice raised felodipine blood levels to 284% of those with water, with lower diastolic pressure and a higher heart rate.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: In 6 men, felodipine bioavailability with grapefruit juice averaged 284% of that with water (range 164 to 469%), diastolic blood pressure was lower, heart rate was higher, and vasodilation side effects were more frequent. Orange juice had no such effect. In 6 healthy men, nifedipine bioavailability with grapefruit juice was 134% of that with water [22].
Population: 6 men with borderline hypertension given felodipine and 6 healthy men given nifedipine [22].
Sources: [22]
Caveats: Two groups of 6 men given single doses. The evidence is for felodipine and nifedipine, both dihydropyridines.

Mixed results2

LimitedStudied in womenUncommon

Breast cancer

Mixed results: one case-control study linked 10 or more years of use to breast cancer, and a pooled analysis and a larger cohort found no link.

The numbers and sources

How common: Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect: In a case-control study, current use for 10 or more years was associated with ductal (OR 2.4, 95% CI 1.2 to 4.9) and lobular (OR 2.6, 95% CI 1.3 to 5.3) breast cancer, with no clear difference between subgroups of the class [23]. A meta-analysis of 11 observational studies found no significant association (OR 1.11, 95% CI 0.93 to 1.33) [24]. In a cohort of 273,152 women, breast cancer occurred at 2.9 per 1,000 a year, and use of calcium channel blockers was not associated with it against other blood pressure drugs (HR 0.97, 95% CI 0.91 to 1.03), with no trend by duration [25].
Population: 1,907 women aged 55 to 74 with breast cancer and 856 controls [23]; 11 observational studies [24]; 273,152 women newly treated with blood pressure drugs [25].
Sources: [23], [24], [25]
Caveats: All observational. The rate shown is for the whole cohort, whichever drug was used [25].

LimitedStudied in pregnancyHow often is not known

Use in pregnancy

The label states that data on amlodipine in pregnancy are too limited to estimate a risk of birth defects or miscarriage.

The numbers and sources

How common: How often is not known: the sources give no rate.
Effect: The amlodipine label states that the limited post-marketing data on use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage [8]. In trials of nifedipine to delay preterm labor, one placebo-controlled trial of 89 women found more maternal adverse effects on the drug (RR 49.89, 95% CI 3.13 to 795.02), and across trials there were fewer maternal adverse effects than with betamimetics (RR 0.36, 95% CI 0.24 to 0.53) [14].
Population: Post-marketing reports described in the label [8]; women in preterm labor in 38 trials [14].
Sources: [8], [14]
Caveats: No rate of birth defects is available from either source.

Claims tested and not found

That amlodipine worsens survival in severe heart failure. In 1,153 people with ejection fraction below 30%, 33% died on amlodipine and 38% on placebo, a 16% lower risk with an interval from 31% lower to 2% higher [18].
That calcium channel blockers raise the risk of cancer overall. In a network meta-analysis of 70 randomized trials, cancer occurred in 2.11% on calcium channel blockers and 2.02% on placebo (OR 1.05, 95% CI 0.96 to 1.13) [26].
That long-acting nifedipine raises deaths in stable angina. In 7,665 people followed a mean 4.9 years, deaths did not differ from placebo (1.64 against 1.53 per 100 patient-years, HR 1.07, 95% CI 0.91 to 1.25) [9].
That diltiazem lowers deaths after a heart attack. In 2,466 people followed a mean 25 months, 167 died on diltiazem and 166 on placebo [17].
That amlodipine slows plaque buildup in coronary arteries. In an ultrasound substudy of 274 people, change in atheroma volume did not differ significantly between amlodipine and placebo [8].

Sources

Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003. https://doi.org/10.1136/bmj.326.7404.1427
Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Lancet. 1997. https://doi.org/10.1016/S0140-6736(97)05381-6
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