Coronary heart disease (CHD) is the leading cause of death worldwide; it is on the rise and has become a true pandemic that respects no borders. (1) It is also the main cause of death in Europe where it accounts for 1.8 million deaths each year. (2) Unfortunately, sudden cardiac death is for many individuals the first manifestation of CHD. (1)

Prevention of CHD ideally begins with primary interventions in persons at increased risk for cardiovascular disease (CVD) but without clinically manifested disease. The physician’s role in primary prevention is to assess the cardiovascular (CV) risk factors, urge lifestyle changes and initiate medical treatment in patients at increased CV risk. However, primary prevention practices are still inadequate and atherosclerosis — the underlying cause of the disease — is often progressing silently for decades until CHD symptoms finally manifest. (1) Individuals with already established CHD have a five- to seven-fold increased risk for recurrent CHD events and, hence, derive greater absolute benefits from the intervention strategies. (3) The contribution of different risk factors to CV risk was demonstrated in a multicenter, case-control study conducted in 52 countries. The study has shown that abnormal lipid levels and hypertension account for approximately 70% of the attributable risk for myocardial infarction (MI) in the population. (4) Over the past decade, the clinical benefit of lipid-lowering and antihypertensive medicines has been, in terms of CV risk reduction, established in numerous randomised controlled trials.

Given the fact that lipid-lowering medicines other than statins have failed to improve clinical outcomes in patients with and without CVD, statins are the first-line pharmacotherapy in the treatment of hyperlipidemia. (1) They have been proven to reduce CV morbidity and mortality as well as the need for coronary artery interventions. (5-8) The Scandinavian Simvastatin Survival Study (4S), which has demonstrated for the first time that treatment with statins changes the incidence of CV events in patients with CHD, turned out to be a milestone in cardiology and evidence-based medicine. Over the 5.4 years of median follow-up of the treatment, statins reduced the risk for major coronary events by 34% and the risk for mortality from all-causes by 30%. There was no difference in non-cardiovascular deaths in the treated and placebo groups. This study has clearly established that statin therapy is safe and that it reduces morbidity and mortality in patients with CHD. The main results of the 4S study are summarised in Table 1. (5)

A host of other large randomised clinical trials followed, which paved the way to widespread use of statins in the CVD prevention. A study by the Cholesterol Treatment Trialists’ (CTT) collaboration analysed and summarised the results of 14 randomised controlled trials involving about 90,000 subjects, of whom 47% had pre-existing CHD. Statins were proven to lower the risk of CHD complications and increase life expectancy. (6) A similar effect was observed in the Cholesterol and Recurrent Events (CARE) study in patients with established CHD, which has shown that cholesterol lowering with statins in patients with previous MI reduces the risk for fatal CHD or nonfatal MI by 24%, fatal MI by 37% and coronary artery bypass surgery by 26%. (7) The observed clinical benefits may be attributed to the antiatherogenic effect of statins, which was assessed in studies using coronary angiography or ultrasound techniques. A study investigating intensive statin therapy and plaque regression was the SATURN trial which compared the effect of rosuvastatin (40 mg daily) and atorvastatin (80 mg daily) in 1,039 patients with CHD for 104 weeks. The results have shown that a reduction of LDL cholesterol levels by more than 50% results in a significant regression of coronary atherosclerosis. (8) Due to the fact that many patients in secondary prevention are not being treated with higher doses of statins, this remains one of the challenges in secondary prevention. (1)

Hyperlipidemia often occurs together with hypertension. (9) Consequently, evidence suggests that therapies targeted at both these CV risk factors lead to greater reductions in the CV risk. (10, 11) A reduction of the systolic blood pressure by 15 mmHg was shown to lead to a 10% CV risk reduction. In addition, a reduction of the total cholesterol by 0.6 mmol/l was associated with a 10% CV risk reduction. However, the same reduction of both risk factors was far more beneficial and resulted in a 45% reduction in the CV risk. (10) Therefore, it’s not surprising that it has been calculated that almost half of the CHD events occurring in hypertensive patients could be prevented by controlling blood pressure and lipids at the same time. (11) Angiotensin-converting enzyme inhibitors (ACEI) have been shown to be effective in secondary prevention of CVD. Evidence of the efficacy of perindopril in reducing the incidence of CV events is already well established. (12) The findings of the European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease (EUROPA) provided clear evidence of the efficacy of perindopril in secondary prevention in patients with stable CHD. (13) Perindopril given at a dose that reduces high blood pressure (8 mg/day) resulted in a 20% reduction in the primary CV endpoint (CV mortality, non-fatal MI, or resuscitated cardiac arrest) when compared with placebo, and this benefit was observed across low-, medium-, and high-risk patients and in a population treated with concomitant lipid-lowering therapy (administered to 69% of patients). Additionally, perindopril reduced CV events in both normotensive and hypertensive patients and, overall, this reduction was potentially greater than it would be expected from the observed decrease from baseline in blood pressure (mean reduction of 5/2- mmHg). This suggests a direct vascular and antiatherosclerotic effect of perindopril. Well-known beneficial effects of perindopril on the vascular structure include reductions in arterial wall hypertrophy and arterial stiffness, and improvements in arterial elasticity. (12) The beneficial effects of perindopril can be linked to its effects leading to an improvement of the endothelial function and breaking the pathophysiological continuum. This slows the rate of progression of CVD and, consequently, improves patient prognosis. (13)

As the prevention of CVD is being one of the most important fields of modern medicine, Krka has made available a wide range of medicines used in the primary and secondary prevention of CVD. Its range of products also includes two most potent statins on the market — atorvastatin (Atoris®) and rosuvastatin (Roswera®), which are available in two additional strengths, atorvastatin 30 mg and 60 mg and rosuvastatin 15 mg and 30 mg. Atorvastatin 60 mg or rosuvastatin 30 mg in particular can provide a suitable maintenance dose for patients with CHD, who usually need a more intensive lipid management. Krka is also one of the few companies offering the entire perindopril portfolio — perindopril (Perineva®), fixed-dose combination of perindopril and indapamide (Co-Perineva®) and fixed-dose combination of perindopril and amlodipine (Dalneva®), which enables a tailored therapeutic approach in a broad range of hypertensive patients.

The efficacy and safety of Krka's cardiovascular medicines are continuously monitored in clinical studies. Till now, more than 110,000 patients have participated in these studies, including patients with CHD.

The results of clinical studies are an important contribution towards improving the management of hyperlipidemia and hypertension in different groups of patients. With evidencebased treatment options, such as statins and ACEI, we could reduce risk factors in CHD patients in order to provide adequate protection against further progression of the disease.