Calcium-channel blockade and incidence of cancer in aged populations

Pahor, Marco; Guralnik, Jack M.; Ferrucci, Luigi; Corti, Maria Chiara; Salive, Marcel E.; Cerhan, James R.; Wallace, Robert B.; Havlik, Richard J.

doi:10.1016/s0140-6736(96)04277-8

Cited by 318 publications

(207 citation statements)

References 33 publications

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“…14 Other findings in the same cohort suggested that treatment with calcium-channel blockers would be associated with a general increased risk of cancer. 12,13 These observational reports 4,[12][13][14][15] left a large margin of uncertainty. With regard to myocardial infarction confounding by indication could not be excluded.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to myocardial infarction confounding by indication could not be excluded. One report 13 associating the use of calcium-channel blockers with cancer was based on 47 exposed cases spread over a wide variety of cancer sites and only provided information on exposure to calcium-channel blockers at baseline. In the same cohort patients taking calcium-channel blockers were more likely to be on treatment with warfarin (6.0% vs 2.6%; P Ͻ 0.001) or aspirin (37.3% vs 29.7%; P Ͻ 0.001), 13 which may have confounded the issue of gastro-intestinal bleeding.…”

Section: Discussionmentioning

confidence: 99%

“…One report 13 associating the use of calcium-channel blockers with cancer was based on 47 exposed cases spread over a wide variety of cancer sites and only provided information on exposure to calcium-channel blockers at baseline. In the same cohort patients taking calcium-channel blockers were more likely to be on treatment with warfarin (6.0% vs 2.6%; P Ͻ 0.001) or aspirin (37.3% vs 29.7%; P Ͻ 0.001), 13 which may have confounded the issue of gastro-intestinal bleeding. 14 A nested case-control analysis based on the information taken from the General Practice Research Database in the United Kingdom collected full information on exposure time, but did not find an increased cancer risk in users of calcium-channel blockers or angiotensin-converting enzyme inhibitors relative to the patients on beta-blockers.…”

Section: Discussionmentioning

confidence: 99%

“…Several arguments fuel the debate. The median follow-up of 2 years in the Syst-Eur trial 3 may have been too short to reveal the suspected adverse effects of dihydropyridines, such as cancer, 12,13 gastrointestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] Syst-Eur 2 will answer these reservations.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 In spite of the positive results in placebo-controlled outcome trials, 3,10,11 the controversy on the use of calcium-channel blockers as first-line antihypertensive agents continues. One of the arguments used is that the median follow-up of the Syst-Eur patients was only 2 years and that therefore they may not have been exposed to nitrendipine 2 for a period sufficiently long to elicit adverse effects, such as cancer, 12,13 gastro-intestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] In keeping with the expert recommendation 8 that wellconducted observational studies may answer issues of drug safety, the Syst-Eur patients will remain in open follow-up to confirm the safety and, ultimately the cost-effectiveness, of antihypertensive therapy based on a dihydropyridine calcium-channel blocker.…”

Section: Rationale and Objective Of Syst-eurmentioning

confidence: 99%

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Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Gąsowski¹,

Staessen²,

Celis³

et al. 1999

J Hum Hypertens

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on behalf of the Systolic Hypertension in Europe InvestigatorsThe Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (у60 years) patients with isolated systolic hypertension (systolic BP у160 mm Hg and diastolic BP Ͻ95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At Keywords: calcium-channel blockade; elderly; dihydropyridine; isolated systolic hypertension IntroductionIn 1989 the European Working Party on High Blood Pressure in the Elderly started the placebo-controlled double-blind Systolic Hypertension in Europe trial (Syst-Eur). 1 Active treatment was initiated with the dihydropyridine calcium-channel blocker nitrendipine 2 with the possible addition of enalapril, hydrochlorothiazide or both drugs. The Syst-Eur trial stopped on 14 February 1997 according to predefined rules, 3 because the second of four planned interim analyses had shown a significant benefit for stroke, the primary end-point. 1 At the Syst-Eur investigators meeting in March 1997, the decision was taken to keep the Syst-Eur patients in followup. This article summarizes the rationale and protocol of this study, named Systolic Hypertension in Correspondence: Dr Jan A Staessen, Klinisch Laboratorium Hypertensie, Inwendige Geneeskunde-Cardiologie, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium Received 14 October 1998; accepted 21 October 1998 the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Cl: 0.8 to 2.6 mm Hg; P Ͻ 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P Ͻ 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and activetreatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, wi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Rationale and Objective Of Syst-eurmentioning

confidence: 99%

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Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Gąsowski¹,

Staessen²,

Celis³

et al. 1999

J Hum Hypertens

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Angiotensin-Converting Enzyme Inhibitors, Calcium Channel Blockers, and Breast Cancer

Meier¹,

Derby²,

Jick³

et al. 2000

Arch Intern Med

113

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Epidemiologic Review of the Calcium Channel Blocker Drugs

Kizer¹,

Kimmel²

2001

Arch Intern Med

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In the setting of soaring popularity, postmarketing studies of calcium channel blockers came to suggest an increase in a variety of major adverse end points. The evidence, however, was largely observational, and large-scale trials capable of addressing the concerns were wanting. Clinical trials now support the safety and efficacy of the long-acting dihydropyridines for patients with both uncomplicated and diabetic hypertension, although conventional therapies and, in the latter case, angiotensin-converting enzyme inhibitors have superior proof of benefit. By contrast, short-acting dihydropyridines should be avoided. In the acute coronary syndromes, beta-blockers remain the treatment of choice; the evidence for nondihydropyridines remains inconclusive. Stable angina calls for beta-blockers as first-line therapy and nondihydropyridines as second-line therapy, whereas in ventricular dysfunction, safety data for nondihydropyridines are lacking. Initial reports of cancer, bleeding, and suicide have been contradicted by subsequent data, making the associations uncertain or unlikely. Remaining questions await completion of ongoing trials to better define the indications for these agents.

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Calcium-channel blockade and incidence of cancer in aged populations

Cited by 318 publications

References 33 publications

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Angiotensin-Converting Enzyme Inhibitors, Calcium Channel Blockers, and Breast Cancer

Epidemiologic Review of the Calcium Channel Blocker Drugs

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