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IMI PROTECT (Work Package 2): Calcium Channel Blocker Treatments and Cancer Risk

18 Years
79 Years
Open (Enrolling)

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Trial Information

IMI PROTECT (Work Package 2): Calcium Channel Blocker Treatments and Cancer Risk

Conducting studies on the possible association between CCBs and cancer using a
pharmaco-epidemiological approach based on data collected in existing databases and cancer
registries is challenging. The challenge lies in working within the limitations of the
available data (in terms of quality and completeness) and simultaneously maximizing the
value of the available data through thoughtful study design and statistical analysis.

CCBs represent a chemically and pharmacologically diverse group of agents that are widely
used for the treatment of hypertension and angina. It has been proposed that CCBs may
interfere with apoptosis, leading to an increased potential for abnormal cell proliferation
and tumor growth. The underlying biological mechanism for this effect is thought to be
linked to the role of transmembrane Ca2+. This hypothesis has been critically reviewed and
results have shown that the action of CCBs on apoptosis are complex with both increases and
decreases in intracellular Ca2+ linked to this form of programmed cell death (2). CCBs have
also been shown to inhibit apoptosis in certain non-transformed cell lines but promote
apoptosis in other non-transformed and transformed cell lines. The results from non-human
genotoxicity studies have shown no link between CCB use and tumor development

Epidemiologic studies have also provided inconsistent results. While only a few follow-up
analyses reported an increased risk for all cancer or breast cancer, further observational
studies have so far provided no evidence to support the hypothesis that long-term use of
CCBs might be carcinogenic. As a whole, these studies have been limited by lack of
statistical power and/or inadequate methods for defining the exposure window of
antihypertensive treatment in relation to the index date (cancer outcome), making the
establishment of a causal relationship between CCBs use and risk of cancer problematical.
Studies often assumed a relatively short period of CCB use (usually between 2 months and 1
year) before entering the study as users. In other cases, information on the use of CCBs was
only available at study entry or during follow-up. Overall, most studies were limited by
follow-up periods that could be considered too brief to measure a carcinogenic effect. The
vast majority of studies collected information from electronic medical or administrative

The current study aims to learn from the experience, strengths and limitations of previous
research to present a best-practice approach to addressing the hypothesis in question.
Combined with the objectives of the PROTECT program, we hope that this study will help to
provide a framework for guiding methodological choices in future research and contribute to
increasing the usefulness and reliability of pharmacoepidemiological studies for
benefit-risk assessment and decision making.

Inclusion Criteria:

- First time users or non-users of a CCB from January 1, 1996 to December 31, 2009

- Patients aged 18 to 79 years

Exclusion Criteria:

- Patients with any cancer recorded in the GPRD or the Danish database prior to cohort

- Patients aged less than 18 years or more than 79 years

Type of Study:


Study Design:

Time Perspective: Retrospective

Outcome Measure:

Change in incidence of primary cancer (all forms) cases, defined by Read codes in GPRD/THIN and ICD-10 codes in the Danish data

Outcome Time Frame:

During Jan 1, 1996 to Dec 31, 2009 , cancer outcomes will be assessed as those occurring six months - 1 year, 1-4 years and more than 5 years following initiation of CCB therapy

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: No Health Authority

Study ID:




Start Date:

November 2011

Completion Date:

August 2014

Related Keywords:

  • Hypertension
  • Calcium channel blockers
  • cancer
  • Hypertension