In this cross-sectional study we have tried to identify the practice of statin use for primary and secondary prevention in the vulnerable segment of the Pakistani population. This study is amongst the few that shed light on the current statin prescription practices and adherence rate in the population of Pakistan [14], [15]. With this study, we hope to contribute towards filling in gaps in knowledge and encourage further work on this important subject.
Using the 2018 ACC/AHA guidelines, we divided our patients into primary (group 1) and secondary (group 2) prevention groups. Out of the 253 subjects in this group, 148 were using statins accounting for a prevalence rate of 58.5% for primary prevention. Compared to this, a recently published US-based study evaluating the prevalence of statin use for primary prevention utilizing the National Health and Nutrition Surveys data (NHANES) from 2013 to 2020, reported a prevalence of 25.5% [16]. Another study by Thompson et. al, based on NHANES data from 2011–2018, reported a prevalence of 34.3% amongst the primary prevention-eligible population [17]. In a single center study similar to ours done in Saudi Arabia, statin was indicted for primary prevention in 285 patients out of which it was being prescribed in 197 patients (69.1%) [18].
Evaluation of statin use for secondary prevention (group 2 ), in patients who have a known history of cardiovascular or cerebrovascular disease, showed that out of the 141 subjects, 127 were taking statin medication, therefore, giving a 90.1% prevalence rate of statin use for secondary prevention. Thompson et al. reported a statin use prevalence rate of 60.3% and 74.5% among those for whom statins are recommended and considered, respectively, according to the 2018 ACC/AHA guidelines in the US population [17]. The Prospective Urban Rural Epidemiology (PURE) cohort study evaluated secondary prevention in 20 high-income, middle-income, and low-income countries, using data collected between 2003 and 2009. The study reported statin use of 3·3% for patients from low-income countries, 4·3% for lower-middle-income countries, 17·6% for upper-middle-income countries, and 66·5% for high-income countries. Nonetheless, the sampling frames employed in prior studies were not nationally representative, and encompassed data gathered prior to the inclusion of statins in the WHO Essential Medicine List in 2007 [19].
The composite prevalence of statin use calculated in our study population is 69.3%. Thompson et al. in the same study reported the composite prevalence to be 47.4%, a value described by them as being “suboptimal” since less than half of the eligible population was on a statin regimen [17]. In another study, done by the CDC, it was reported that about 54.5% of the eligible patients in the US were using statins [20]. One reason for these massive differences between our study and those studying the US population could be that our sample population is derived from a hospital setting. The effect due to the change in setting is reflected in a cross-sectional study across 140 specialty clinics in the US, that reported the statin use prevalence of 62.3% and 82.2% for primary and secondary prevention, respectively [21]. Our study is based on a single center, CMH Lahore, which provides medications free of charge to eligible patients, and is catering mostly to the urban population. We believe that this might further mask any potential lack of adherence due to the unaffordability of patients that might be present otherwise in the general population. Although our results meet the minimum statin use criteria in the eligible population, not all hospitals in Pakistan provide free medication and so the statin use statistics in other centers and settings may be different. We would like to highlight the importance of collecting data on primary and secondary prevention, due to the prevalent trends of hypertension, Diabetes, ISHD, and other predisposing factors in our population, placing them at significant risk.
Our study, as well as the one by Thompson-Paul et. al., presented a higher prevalence of statin use in the secondary prevention group as compared to the primary prevention group [17]. In our study, this difference is by a factor of 1.558. A study done in New Zealand reflected the same patterns, with higher adherence and lower discontinuation rate in the secondary prevention group compared to the primary prevention group by an almost identical factor of 1.55 [22]. In our opinion, this observation may be due to increased wariness and caution amongst patients in the secondary prevention group after having suffered a serious cardiovascular or cerebrovascular event. Similar profiles of adverse effects in primary and secondary prevention groups, with a greater health benefit in the latter may also justify the higher statin prevalence seen for secondary prevention. This reasoning has again been backed by Sigglekow et. al in their study [22].
The 2018 ACC/AMA guidelines focus on patient-physician shared decision making and multidisciplinary team based approach for individual patients. The severity of CVD risk factors, age of the patient, 10 year ASCVD risk, and LDL levels are taken into consideration when prescribing statin [8]. For primary prevention, high intensity statin therapy (with a goal of ≥ 50% reduction in LDL-C) is recommended for Individuals:
Similarly, moderate intensity statin therapy (with a goal of ≥ 30% reduction in LDL-C) is recommended for:
For secondary prevention, high-dose statin therapy is to be instituted to reduce LDL-C by 50% or more. Further adjustment of dose is based on patient tolerability and side effect profile. The daily drug regimen for moderate-intensity statin varies with the choice of statin, these regimens include: 40–80 mg of lovastatin or pravastatin, 20–40 mg of simvastatin, 10–20 mg of Atorvastatin or 5–10 mg of Rosuvastatin [23]. Similarly for high-intensity statin therapy, either 40–80 mg Atorvastatin or 20–40 mg Rosuvastatin regimen are recommended.
Regarding dose determination, our data showed that 136/148 (91.89%) subjects in the primary prevention group were receiving moderate-intensity statins, 10/148 (6.76%) were receiving high-intensity statins. It is to be noted that our primary prevention group comprised mostly of subjects with diabetes who were older than 40; In the secondary prevention group, 101/127 (79.53%) were receiving moderate-intensity statins and 24/127 (18.90%) were receiving high-intensity statins. Interestingly, less than one-fifth of the patients in the secondary prevention group were taking high-intensity statin therapy when it should be the initially instituted regimen. This cannot be explained by dose adjustment which is only about 15.7% in this group. So, although statin use prevalence is above average in our population, it is not necessarily up to par with the current guidelines, evident by the low rates of high-intensity statin use.
The incidence of adverse effects in our sample population was low overall, with about 2.2% of the statin users experiencing myalgias and 1.8% reporting a history of deranged liver function tests leading to dose adjustment or statin discontinuation. This is in congruence with another study done in Pakistan on the frequency of statin mediated adverse effects. The study noted incidence rates of 6.7%, 0.8% and 2.9% for myalgia, myositis and hepatitis, respectively [24]. Keeping these figures in mind, we can discuss the potential for a more robust approach to high intensity statin prescription. There is some apprehension among the pakistani medical community when it comes to statins, and they seem to take a more cautious approach to prescribing it. A high-intensity regimen, in the eligible population, effectively lowers the LDL-c levels and has been associated with lower cardiovascular adverse events [6]. Apart from the LDL lowering effects, statins are believed to have a pleiotropic profile with an effect on the inflammatory mediators. A Randomised trial published in the New England journal evaluated statin’s effect on the C- reactive protein, and reported a significantly lowering effect on cardiovascular and all cause mortality with statin use in patients without hyperlipidemia [25]. Now although the findings of this study have been disputed by some, we can not diminish the possibility of its alternative effects. Thus pressing further on the importance of adhering to the guidelines, especially regarding high-intensity statin regimen.
Regarding the limitations in our study, we could not calculate the ASCVD risk for most of the patients due to various reasons; most notably, the unavailability of a recent lipid profile and/or fresh blood pressure reading. Since most of the patients were already receiving statin therapy, we assume that the prescribing physician had calculated the 10-year risk and accordingly prescribed statin therapy. However, this also highlights how current health practices do not encourage or increase awareness of regular lipid profile testing and BP monitoring, as well as availability of these findings on days of clinical visit. This has also been observed by another study that highlighted the inadequate practice of lipid assessment in Pakistan and how that compromises therapy optimization [9]. Secondly, the setting of our study, a single urban center with the majority of patients being entitled to get free treatment and medication. Although it indicates good prescribing practices of the physicians, our figures may not reflect the true number of patients being prescribed and using statin as per indications and recommendations in our country. There are definite economic constraints and access to appropriate health facilities. Therefore, we recommend such studies at a national level considering the high burden of diabetes and hypertension in our local population making it all the more solid ground to put efforts in the direction of preventive medicine. Complications of these diseases and their management lead to a huge toll on the health economy.