STATIC - Statin Termination in Cancer

There are many guidelines on when to start drug treatment, but surprisingly few guidelines on how and when to stop drugs. For example, there are currently no clear guidelines on when to stop preventive medications such as statins in patients in palliative cancer care. According to previous studies, these drugs are often deprescribed far too late in the process, often close to death. This can lead to unwanted side effects, such as muscle weakness, increased fatigue, and also contribute to unnecessary drug costs and unnecessary environmental impact. In the STATIC I study the safety and effects of early deprescribing of statins in palliative cancer care is explored. The primary aim of the STATIC study is to study the change in LDL-levels (mmol/L) after statin termination. The secondary outcomes includes change in levels of other steroids (cholesterol, HDL, Q10, 25-hydroxyvitamin D, lanosterol), change in muscle strength, cardiovascular events, fatigue and quality of life after statin deprescribing. STATIC I is a pilot study to optimize the design for the randomized study STATIC II. The study aim at including 40 patients with advanced cancer within specialized palliative care with an expected survival time \>1 month to \<1 year (surprise question 1 year). At start of the study statins are deprescribed and the patients are followed for 12 weeks. Data collection is performed at baseline, 2, 4, 8 and 12 weeks. A control group (n=40) comprising patients with advanced cancer and no ongoing statin treatment, are included from the same specialized palliative care units. The control group is followed for 12 weeks regarding muscle strength and symptom burden. The current studies can provide important and valuable knowledge on the safety and effects of early describing.

STATIC - statin termination in cancer Purpose and Aims To reduce overtreatment of statins in palliative cancer care. To this end, a prospective pilot study in patients with advanced cancer to evaluate effects and safety of deprescribing statins is performed. Hypotheses Statin treatment might do more harm than good in patients with advanced cancer with a limited life expectancy (less than 1 year) and should be discontinued earlier in the disease trajectory than is standard practice today. Background Palliative Care and deprescribing Palliative medicine aims at providing relief from symptoms in incurable diseases and at maintaining functions and a high quality of life (QoL), i.e. "to live every day until you die". In medical treatment in palliative care, side effects should be minimized and should not outweigh possible beneficial effects. Prescription of drugs often follows clear guidelines. However, there are few or no guidelines for when drugs should be discontinued, i.e. deprescribed. At the end of life, many medications can be directly harmful. As an example, the patient's life expectancy may be shorter than the time required for preventive medications to have an effect and the patients will only get side effects without any benefits (1). Such overtreatment can lead to unnecessary adverse effects and contribute to unnecessary costs. In addition, a large burden of tablets is often troublesome for patients. Today, there are very few prospective studies performed on deprescribing. However, there is one randomized trial on deprescribing statins (2). This study showed that early deprescribing of statins (the last year before death) was associated with improved QoL among patients with early statin deprescription and no increased risk of cardiovascular events (2). However, due to a large drop-out rate, the primary aim of this study could not be full-filled, i.e. to study the safety of discontinuation. Moreover, in that study no cholesterol levels were measured. There might be an overmedication of statins in patients in palliative cancer care and probably these drugs often can be deprescribed earlier. In previous retrospective studies, described below, it is shown that statins are often deprescribed very late in the disease trajectory. Statins Statins lower blood cholesterol levels by inhibiting the endogenous synthesis of cholesterol in the liver by inhibiting the enzyme HMG CoA reductase, the rate-regulating enzyme in steroid synthesis. During statin treatment, total-cholesterol and LDL-cholesterol decreases, while HDL (the "good" cholesterol) increases. Statins have been shown to be effective drugs in reducing cardiovascular events and death (3). The most common side effects of statin treatment are muscle weakness, muscle pain and muscle fatigue (4). Cholesterol levels in the blood are affected both by the endogenous synthesis in the liver (that is inhibited by statins) but also by diet. The best way to measure the effect of statins on HMG- trial.show_full_description

Inclusion Criteria intervention arm: * ≥ 18 years, * "No"-answer to the "surprise question" 1 year: Would you be surprised if this patient died in the next year? (this is a common and validated prognostic tool in palliative care) * advanced cancer * ongoing palliative care at the the unit study units * treatment with statins ≥ 3 months for primary or secondary prevention before study inclusion Inclusion Criteria control-group: * Same as above but no statin treamnet Exclusion Criteria:h * Cognitive impairment * Does not understand the Swedish language * Known homozygous or double heterozygous familial hypercholesterolemia * Active cardiovascular disease or sufficient risk of active cardiovascular disease that requires ongoing medication with statins (assessed by a specialist in cardiology) * myositis symptoms * Other contraindications to deprescribe statins.