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Cardiovascular disease (CVD), the leading cause of death and disability worldwide, imposes huge healthcare costs to society and significant burdens to patients. It is estimated that 18 million deaths occurred from CVD annually worldwide [1]. Over three quarters of CVD deaths take place in lowand middle-income countries including Iran. Therefore, developing and implementing public health strategies is necessary for primary and secondary prevention of CVD [2]. Many of these deaths may be prevented with use of approved medications. Guidelines strongly recommend the use of medicines including aspirin, statins, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptors blockers (ARBs) for prevention of CVD risk factors including hypertension, dyslipidemia and thrombosis [3]. Nowadays fixed-dose combination therapy is recommended. However, the possible superior clinical effect of polypill compared to statins alone for primary prevention of CVD in intermediate risk population has not been investigated yet. According to the importance of dyslipidemia, current guidelines recommend statins in the primary prevention of CVD based on predicted cardiovascular risk approach. The American College of Cardiology and American Heart Association (ACC/AHA) statin guidelines recommend high and moderate-high intensity statin therapy for all adults with low density lipoprotein-cholesterol (LDL-C) equal or greater than 190 mg/dl and risk of CVD ≥7.5% over 10 years, respectively [4]. Moreover, ACC/AHA recommends moderate-intensity therapy for adults without diabetes mellitus, aged 40–75 years with 5–7.5% risk of CVD over 10 years [5]. In this regard, Khalili et al. showed that the 2013 ACC/AHA guideline on statin therapy could be useful for both moderate and intensive treatment of hypercholesterolemia and prevention of CVD events in Iranian population [6]. However, Thanassoulis et al. (2016) revealed that an individualized statin benefit approach based on predicted absolute risk reduction over 10 years in comparison with the 10-year risk-based approach could better identify eligible lowerrisk individuals who meaningfully benefit from statin treatment [7]. In spite of probable statins adverse effects like muscle pain and increasing serum blood sugar, meta-analysis of randomized trials which evaluated the effect of statin on primary prevention of CVD documented that 1 mmol per liter reduction of LDL-C with statin was associated with 25% lower risk of CVD events [8]. Yusuf et al. (2016) recently published the primary results of the Heart Outcomes Prevention Evaluation (HOPE)-3 study, a multicenter, international, double-blind, randomized, placebo-controlled trial [9–11]. This study was conducted on 12705 intermediate-risk person of various ethnic backgrounds on six continents and 21 countries who did not have CVD with no specific lipid or blood pressure levels for entry. Participants were randomly assigned to rosuvastatin group at a dose of 10 mg per day or placebo and were also randomly assigned to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo for a median follow-up of 5.6 years. They revealed that treatment with rosuvastatin resulted in a 24% lower risk of cardiovascular events compared to placebo. However, blood-pressure lowering treatment did not significantly reduce the risk of cardiovascular events in this intermediate-risk population without cardiovascular disease. Moreover, the comparison of the combined intervention effects with placebo showed no more benefit than rosuvastatin alone [9–11]. The results of HOPE-3 study provide the evidence in support of statin use for primary * Correspondence: shirinhasanir@yahoo.com; sh_hasani@sina.tums.ac.ir Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Statins alone or polypill for primary prevention of cardiovascular diseases