The Polypill in the Prevention of Cardiovascular Disease

Abstract

Overwhelming data from clinical trials show that pharmacological interventions with aspirin, statins and blood pressure (BP)-lowering agents considerably reduce the risk of cardiovascular events and total mortality. Therefore, current international treatment guidelines recommend to prescribe statins, BP-lowering agents, and, where benefits outweigh risks, antiplatelet therapy with little constraints to individuals at high risk of cardiovascular disease, such as patients with established cardiovascular disease or those at equivalent high risk. However, in clinical practice large gaps between indicated therapy and prescribed medication can be observed worldwide, with very low rates of use of effective therapies in middle- and low-income countries. Various barriers may underlie suboptimal prescribing rates and low treatment continuation rates in high-risk patients, which include the complexity of preventive treatment regimens for both doctors and patients, inequities in health care delivery and medication costs. A fixed-dose combination pill, frequently called a cardiovascular polypill, containing aspirin, a statin and ≥1 BP-lowering agents has been suggested to moderate prescription to indicated therapy and reduce physicians’ and patients’ barriers in order to optimize the prevention of cardiovascular diseases in the general population, in subjects with elevated vascular risk and in high-risk patients. The aim of this thesis is to provide evidence on the efficacy, safety and tolerability of the polypill in patients at high risk of cardiovascular disease. In addition, attention is given to aspects of feasibility, such as timing of intake and patients’ preferences regarding therapy. Patients with established cardiovascular disease or those at equivalent high risk were shown to often already use a combination of aspirin, a statin and BP-lowering agents as recommended in usual care. A combination of these drugs was shown to be effective in preventing (subsequent) cardiovascular events. Therefore, patients at high risk of cardiovascular could be considered as the ‘low hanging fruit’ for the implementation of a polypill-based treatment strategy. Switching to a polypill containing aspirin, simvastatin and two BP lowering agents was found to result in improved adherence and lower levels of low-density lipoprotein (LDL)-cholesterol and systolic BP among patients at high risk of cardiovascular disease. Additionally, the risk of cardiovascular disease was approximately 10% lower compared to continuing usual care irrespective of the treatment received at baseline. Differences in atherosclerosis as measured with carotid intima media thickness or 24-hour ambulator BP between the polypill group and the usual care group could not be shown. Importantly, carotid intima media thickness progression and ambulatory BP were not adversely effected by the polypill-based treatment strategy. The polypill was well tolerated. As the components of the polypill are used at different times of the day, the optimal time for using the polypill was uncertain. It was shown that the reduction of LDL-cholesterol and systolic BP was optimal when the polypill was administered in the evening compared to the morning. Importantly patients highly preferred to be treated with a polypill over the individual pills, resulting in higher adherence levels. The results of this thesis strongly suggest a potential role for the polypill in the prevention of cardiovascular disease.