ATORVASTATIN CALCIUM Tablet, Film Coated [Unit Dose Services]

14.1 Protection against Coronary Disease

Within the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the result of atorvastatin calcium on fatal and non-fatal heart disease was assessed in 10,305 hypertensive patients 40 to 80 years old (mean of 63 years), with no previous myocardial infarction with TC levels ≤251 mg/dL (6.5 mmol/L). Furthermore, all patients had a minimum of three of the following cardiovascular risks: male gender (81.1%), age &gt55 years (84.5%), smoking (33.2%), diabetes (24.3%), good reputation for CHD inside a first-degree relative (26%), TC:High-density lipoprotein &gt6 (14.3%), peripheral vascular disease (5.1%), left ventricular hypertrophy (14.4%), prior cerebrovascular event (9.8%), specific ECG abnormality (14.3%), proteinuria/albuminuria (62.4%). Within this double-blind, placebo-controlled study, patients were given anti-hypertensive therapy (Goal BP &lt140/90 mm Hg for non-diabetics &lt130/80 mm Hg for diabetics) and allotted either to atorvastatin calcium 10 mg daily (n=5168) or placebo (n=5137), utilizing a covariate adaptive method which required into consideration the distribution of nine baseline characteristics of patients already enrolled and minimized the imbalance of individuals characteristics over the groups. Patients were adopted for any median time period of 3.three years.

The result of 10 mg/day’s atorvastatin calcium on fat levels looked like that observed in previous numerous studies.

Atorvastatin calcium considerably reduced the speed of coronary occasions [either fatal heart disease (46 occasions within the placebo group versus. 40 occasions within the atorvastatin calcium group) or non-fatal MI (108 occasions within the placebo group versus. 60 occasions within the atorvastatin calcium group)] having a relative risk decrease in 36% [(according to incidences of just one.9% for atorvastatin calcium versus. 3.% for placebo), p=.0005 (see Figure 1)]. The danger reduction was consistent no matter age, smoking status, weight problems, or existence of kidney disorder. The result of atorvastatin calcium was seen no matter baseline LDL levels. Because of the few occasions, recent results for women were inconclusive.

Figure 1: Aftereffect of Atorvastatin Calcium 10 mg/day on Cumulative Incidence of Non-Fatal Myocardial Infarction or Heart Disease Dying (in ASCOT-LLA)

                                         Figure-01

Atorvastatin calcium also considerably decreased the relative risk for revascularization procedures by 42%. Even though the decrease in fatal and non-fatal strokes didn’t achieve a pre-defined significance level (p=.01), a good trend was observed having a 26% relative risk reduction (incidences of just one.7% for atorvastatin calcium and a pair of.3% for placebo). There wasn’t any factor between your treatment groups for dying because of cardiovascular causes (p=.51) or noncardiovascular causes (p=.17).

Within the Collaborative Atorvastatin Diabetes Study (CARDS), the result of atorvastatin calcium on coronary disease (CVD) endpoints was assessed in 2838 subjects (94% white-colored, 68% male), ages 40 to 75 with diabetes type 2 according to WHO criteria, without prior good reputation for coronary disease with LDL ≤ 160 mg/dL and TG ≤ 600 mg/dL. Additionally to diabetes, subjects had 1 or a lot of following risks: current smoking (23%), hypertension (80%), retinopathy (30%), or microalbuminuria (9%) or macroalbuminuria (3%). No subjects on hemodialysis were signed up for the research. Within this multicenter, placebo-controlled, double-blind medical trial, subjects were at random allotted either to atorvastatin calcium 10 mg daily (1429) or placebo (1411) inside a 1:1 ratio and were adopted for any median time period of 3.nine years. The main endpoint was the appearance of the major cardiovascular occasions: myocardial infarction, acute CHD dying, unstable angina, coronary revascularization, or stroke. The main analysis was time to first occurrence from the primary endpoint.

Baseline characteristics of subjects were: mean chronilogical age of 62 years, mean HbA1c 7.7% median LDL-C 120 mg/dL median TC 207 mg/dL median TG 151 mg/dL median High-density lipoprotein-C 52 mg/dL.

The result of atorvastatin calcium 10 mg/day on fat levels looked like that observed in previous numerous studies.

Atorvastatin calcium considerably reduced the speed of major cardiovascular occasions (primary endpoint occasions) (83 occasions within the atorvastatin calcium group versus. 127 occasions within the placebo group) having a relative risk decrease in 37%, HR .63, 95% CI (.48, .83) (p=.001) (see Figure 2). An impact of atorvastatin calcium was seen no matter age, sex, or baseline fat levels.

Atorvastatin calcium considerably reduced the chance of stroke by 48% (21 occasions within the atorvastatin calcium group versus. 39 occasions within the placebo group), HR .52, 95% CI (.31, .89) (p=.016) and reduced the chance of MI by 42% (38 occasions within the atorvastatin calcium group versus. 64 occasions within the placebo group), HR .58, 95.1% CI (.39, .86) (p=.007). There wasn’t any factor between your treatment groups for angina, revascularization procedures, and acute CHD dying.

There have been 61 deaths within the atorvastatin calcium group versus. 82 deaths within the placebo group (HR .73, p=.059).

Figure 2: Aftereffect of Atorvastatin Calcium 10 mg/day promptly to Occurrence of Major Cardiovascular Event (myocardial infarction, acute CHD dying, unstable angina, coronary revascularization, or stroke) in CARDS

                                          Figure-02

Within the Treating to New Targets Study (TNT), the result of atorvastatin calcium 80 mg/day versus. atorvastatin calcium 10 mg/day around the decrease in cardiovascular occasions was assessed in 10,001 subjects (94% white-colored, 81% male, 38% ≥65 years) with clinically apparent heart disease who’d achieved a target LDL-C level &lt130 mg/dL after finishing an 8-week, open-label, run-in period with atorvastatin calcium 10 mg/day. Subjects were at random allotted to either 10 mg/day or 80 mg/day’s atorvastatin calcium and adopted for any median time period of 4.nine years. The main endpoint was time-to-first occurrence of the following major cardiovascular occasions (MCVE): dying because of CHD, non-fatal myocardial infarction, resuscitated cardiac event, and fatal and non-fatal stroke. The mean LDL-C, TC, TG, non-High-density lipoprotein, and High-density lipoprotein levels of cholesterol at 12 days were 73, 145, 128, 98, and 47 mg/dL during treatment with 80 mg of atorvastatin calcium and 99, 177, 152, 129, and 48 mg/dL during treatment with 10 mg of atorvastatin calcium.

Treatment with atorvastatin calcium 80 mg/day considerably reduced the speed of MCVE (434 occasions within the 80 mg/day group versus. 548 occasions within the 10 mg/day group) having a relative risk decrease in 22%, HR .78, 95% CI (.69, .89), p=.0002 (see Figure 3 and Table 5). The general risk reduction was consistent no matter age (&lt65, ≥65) or gender.

Figure 3: Aftereffect of Atorvastatin Calcium 80 mg/day versus. 10 mg/day promptly to Occurrence of Major Cardiovascular Occasions (TNT)

                                                  Figure-03

From the occasions that comprised the main effectiveness endpoint, treatment with atorvastatin calcium 80 mg/day considerably reduced the speed of non-fatal, non-procedure related MI and fatal and non-fatal stroke, although not CHD dying or resuscitated cardiac event (Table 5). From the predefined secondary endpoints, treatment with atorvastatin calcium 80 mg/day considerably reduced the speed of coronary revascularization, angina, and hospitalization for heart failure, although not peripheral vascular disease. The decrease in the speed of CHF with hospitalization was just noticed in the 8% of patients having a prior good reputation for CHF.

There wasn’t any factor between your treatment groups for those-cause mortality (Table 5). The proportions of subjects who experienced cardiovascular dying, such as the aspects of CHD dying and fatal stroke, were numerically smaller sized within the atorvastatin calcium 80 mg group compared to the atorvastatin calcium 10 mg treatment group. The proportions of subjects who experienced noncardiovascular dying were numerically bigger within the atorvastatin calcium 80 mg group compared to the atorvastatin calcium 10 mg treatment group.

Within the Incremental Reduction in Endpoints Through Aggressive Fat Lowering Study (IDEAL), treatment with atorvastatin calcium 80 mg/day was when compared with treatment with simvastatin 20 to 40 mg/day in 8,888 subjects as much as 80 years old with past CHD to evaluate whether decrease in CV risk might be achieved. Patients were mainly male (81%), white-colored (99%) by having an average chronilogical age of 61.many years, as well as an average LDL-C of 121.5 mg/dL at randomization 76% were on statin therapy. Within this prospective, randomized, open-label, blinded endpoint (PROBE) trial without any run-in period, subjects were adopted for any median time period of 4.8 years. The mean LDL-C, TC, TG, High-density lipoprotein, and non-High-density lipoprotein levels of cholesterol at Week 12 were 78, 145, 115, 45, and 100 mg/dL during treatment with 80 mg of atorvastatin calcium and 105, 179, 142, 47, and 132 mg/dL during treatment with 20 to 40 mg of simvastatin.

There wasn’t any factor between your treatment groups for that primary endpoint, the speed of initial coronary event (fatal CHD, non-fatal MI, and resuscitated cardiac event): 411 (9.3%) within the atorvastatin calcium 80 mg/day group versus. 463 (10.4%) within the simvastatin 20 to 40 mg/day group, HR .89, 95% CI ( .78, 1.01), p=.07.

There have been no significant variations between your treatment groups for those-cause mortality: 366 (8.2%) within the atorvastatin calcium 80 mg/day group versus. 374 (8.4%) within the simvastatin 20 to 40 mg/day group. The proportions of subjects who experienced CV or non-CV dying were similar for that atorvastatin calcium 80 mg group and also the simvastatin 20 to 40 mg group.

14.2 Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

Atorvastatin calcium reduces total-C, LDL-C, VLDL-C, apo B, and TG, and increases High-density lipoprotein-C in patients with hyperlipidemia and mixed dyslipidemia. Therapeutic fact is seen within 2 days, and maximum fact is usually achieved within 4 days and maintained during chronic therapy.

Atorvastatin calcium works well in a multitude of patient populations with hyperlipidemia, with and without hypertriglyceridemia, in women and men, as well as in the seniors.

In 2 multicenter, placebo-controlled, dose-response studies in patients with hyperlipidemia, atorvastatin calcium given like a single dose over 6 days, considerably reduced total-C, LDL-C, apo B, and TG. (Pooled answers are provided in Table 6.)

TABLE 6. Dose Response in Patients With Primary Hyperlipidemia (Adjusted Mean % Vary From Baseline)a

In patients with Fredrickson Types IIa and IIb hyperlipoproteinemia pooled from 24 controlled trials, the median (25th and 75th percentile) percent changes from baseline in High-density lipoprotein-C for atorvastatin calcium  10, 20, 40, and 80 mg were 6.4 (-1.4, 14), 8.7 (, 17), 7.8 (, 16), and 5.1 (-2.7, 15), correspondingly. Furthermore, research into the pooled data shown consistent and significant decreases as a whole-C, LDL-C, TG, total-C/High-density lipoprotein-C, and LDL-C/High-density lipoprotein-C.

In three multicenter, double-blind studies in patients with hyperlipidemia, atorvastatin calcium was when compared with other statins. After randomization, patients were treated for 16 days with either atorvastatin calcium 10 mg each day or perhaps a fixed dose from the comparative agent (Table 7).

TABLE 7. Mean Percentage Vary From Baseline at Endpoint (Double-Blind, Randomized, Active-Controlled Trials)

The outcome on clinical connection between the variations in fat-altering effects between treatments proven in Table 7 isn’t known. Table 7 doesn’t contain data evaluating the results of atorvastatin 10 mg and greater doses of lovastatin, pravastatin, and simvastatin. The drugs compared within the studies summarized within the table aren’t always interchangeable.

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