Coronary heart disease (CHD) has assumed epidemic proportions in India & by 2010, 60% of the world's heart disease is expected to occur in India . Chronic stable angina is the commonest initial manifestation of CHD. It is observed that despite an extensive use of conventional therapy, 85% of patients still complain of anginal symptoms. Also, the hemodynamic adverse events limit the use of current antianginal agents.

Ranolazine is the first agent to be approved for angina after almost a decade. Studies with ranolazine have established its efficacy both as a monotherapy & in combination with other antianginal agents. Ranolazine reduces anginal symptoms and improves the quality of life without any effect on hemodynamic parameters. It is well tolerated with its safety documented up to 3 years. Interestingly, it also exhibits antiarrhythmic properties. Recently, ranolazine has been approved as a first-line agent for management of angina by US FDA in November 2008. Taking the above into consideration Cipla has recently launched ranolazine under the brand name CORVELA .

It is recommended to initiate with 1 tablet of CORVELA (ranolazine extended release 500 mg) twice daily and increase it to maximum of 2 tablets of CORVELA twice daily, based on clinical symptoms. The maximum dose of CORVELA should be limited to 500 mg twice daily in patients on diltiazem, verapamil, and other moderate CYP3A inhibitors (eg. erythromycin, fluconazole). The dose should be down-titrated based on clinical response in patients concomitantly treated with P-gp inhibitors, such as cyclosporine.

CORVELA should not be taken with strong inhibitors of CYP3A (eg. ketoconazole, itraconazole, clarithromycin), with inducers of CYP3A (eg. rifampin, rifabutin, refapentin, phenytoin, phenobarbital, cabamazepine) & by patients with clinically significant hepatic impairment.

 

Hypertension is highly prevalent throughout the world with 1 out of every 5 adult Indian having hypertension. Studies have shown that any monotherapy is able to normalize BP in only about 20-30% of hypertensives while c ombination therapy improves the BP response rate in 75-90%. Currently, focus is increasingly on the use of RAAS blocker-CCB combination in the management of hypertension.

 CRESAR AM is a fixed dose combination of telmisartan 40 mg and amlodipine 5 mg. CRESAR AM provides a balanced and additive BP reduction. In addition, the combination provides effective cardioprotection, vascular protection & renoprotection. In addition, edema a commonly seen side-effect of amlodipine monotherapy is attenuated by addition of a telmisartan; which improves the safety profile of the combination. Morever, CRESAR AM is a combination that can be safely used for management of hypertensives with any comorbid condition.

The recommended dose is one tablet of CRESAR AM once daily. If necessary, the dose may be increased to two tablets of CRESAR AM once daily. In small, fragile or elderly patients or patients with hepatic insufficiency, the patient should be initiated on separate tablets of telmisartan 40 mg & amlodipine 2.5 mg. When the patient is able to tolerate up to 5 mg of amlodipine, the patient may be shifted to one tablet of CRESAR AM.

 

Hypertension is highly prevalent worldwide, with India soon heading towards being hypertension capital of the world. Similarly, coronary heart disease has assumed epidemic proportions in India & b y 2010, 60% of the world's heart disease is expected to occur in India .

Monotherapy for hypertension has shown to normalize BP in only about 20-30% of patients while c ombination therapy is able to improve the BP response rate in 75-90% of patients. In patients with angina who do not get symptom relief by monotherapy, combination offers a better alternative to increasing the dose of monotherapy.

METOLAR AM is a fixed dose combination of metoprolol extended release and amlodipine available in 2 strengths, METOLAR AM 25 (metoprolol succinate 25 mg + amlodipine 5 mg) & METOLAR AM 50 (metoprolol succinate 50 mg + amlodipine 5 mg). The combination provides a balanced and additive effects in both hypertension & angina management & is well-tolerated.

The recommended dosage of METOLAR AM 25/ 50 is one tablet once daily. In small, fragile or elderly individuals or patients with hepatic insufficiency , initiate on separate tablets of metoprolol extended-release and amlodipine 2.5 mg both once daily. When these patients are able to tolerate up to 5 mg of amlodipine, then they can be shifted to METOLAR AM.

 

Platelet aggregation plays a substantial role in the pathophysiology of acute coronary syndromes (ACS) and in thrombotic complications of percutaneous coronary intervention (PCI). The glycoprotein (GP) IIb/IIIa receptor is the final common pathway of platelet aggregation and thus, represents an ideal therapeutic target for blocking coronary thrombosis. Therefore, GP IIb/IIIa receptor blockers namely, eptifibatide, abciximab and tirofiban have been evaluated for their efficacy in a variety of clinical settings.

Eptifibatide is unique amongst GP IIb/IIIa inhibitors and is approved by US FDA in both non-ST elevation ACS (NSTEACS) and elective PCI. On the contrary, abciximab is approved only in elective PCI and tirofiban only in NSTEACS. Thus, eptifibatide is the only GP IIb/IIIa inhibitor approved for both NSTEACS and PCI. Further, eptifibatide is associated with the most consistent inhibition of platelet aggregation as well as significantly faster & greater magnitude of inhibition of platelet aggregation amongst the available GP IIb/IIIa receptor blockers.

INTIFLO (eptifibatide) injection is available in two strengths- 0.75 mg/ml and 2 mg/ml. The recommended dose of INTIFLO is as follows:

Indication	Normal renal function	Renal impairment (creatinine clearance < 50 ml/min)
NSTEACS	IV bolus 180 µg/kg, followed by continuous infusion of 2 µg/kg/min until hospital discharge or CABG initiation (total 72 hrs)	IV bolus 180 µg/kg, followed by continuous infusion of 1 µg/kg/min until hospital discharge or CABG initiation (total 72 hrs)
	If patient is to undergo PCI while receiving INTIFLO , continue INTIFLO up to hospital discharge, or 18-24 hours after procedure (total 96 hrs)
PCI	IV bolus 180 µg/kg before PCI, followed by continuous infusion of 2 µg/kg/min and second 180 µg/kg bolus 10 minutes after the first	IV bolus 180 µg/kg before PCI, followed by continuous infusion of 1 µg/kg/min and second 180 µg/kg bolus 10 minutes after the first
	INTIFLO should be continued until hospital discharge, or for up to 18-24 hours (min 12 hrs) Discontinue INTIFLO in patients undergoing CABG

 

In practice, the blood pressure goals set by hypertension management guidelines are not being achieved in majority of patients. One important reason for poor hypertension control rates is the inability of monotherapy to achieve blood pressure goals in many patients. Therefore, combination therapy is the need in nearly 2/3 rd of hypertensives to attain the target blood pressure levels.

One of the most common combination therapies for hypertension comprises a b blocker with a thiazide diuretic. Nebizide is a fixed dose combination of 5 mg nebivolol and 12.5 mg hydrochlorothiazide. Nebivolol is an outstanding, third generation highly selective b blocker with NO-mediated vasodilation whereas hydrochlorothiazide is a time-tested diuretic which has been used clinically for more than 45 years. Studies have shown the combination to offer additive BP reduction as compared to both monotherapies with no increase in adverse events. Further, the beneficial effects on lipids and glucose metabolism due to unique NO-mediated vasodilation with nebivolol can counteract the adverse effects of hydrochlorothiazide on lipids and glucose, thereby offering an advantage over other b blocker-diuretic combinations. In addition, the combination can also improve endothelial function on account of NO-mediated vasodilation with nebivolol and can yield added improvements in left ventricular function.

The recommended dose of NEBIZIDE is one tablet daily. In patients with severe renal impairment (CICr <30 mL/min) and moderate hepatic impairment, the initial dose of nebivolol should not exceed 2.5 mg of nebivolol in NEBIZIDE . NEBIZIDE is being made available across the country.

 

Cardiac arrhythmias are a major source of morbidity and mortality in the developing and the developed world. Although amiodarone is one of the oldest drugs with extensive evidence on its efficacy, its diverse adverse effect profile can limit its long-term use. Amongst other antiarrhythmic drugs, sotalol is a unique antiarhythmic drug. It is a class III antiarrhythmic; in addition to blocking the potassium channels, it is a non-selective b blocker.

Unlike amiodarone, sotalol has high bioavailability of 100%, no pharmacokinetic drug interactions and no need for any loading doses. Sotalol has been shown to be superior to amiodarone in ventricular arrhythmias and in supraventricular arrhythmias, sotalol has comparable efficacy with superior safety profile as compared to amiodarone. Sotalol has been demonstrated to be superior to b blockers in ventricular arrhythmias. Further, sotalol is also superior or at least comparable to class I drugs (procainamide, quinidine, propafenone, quinidine, mexiletinie, imipramine, piremenol) in ventricular and supraventricular arrhythmias. The major advantage of sotalol over amiodarone is that it does not exhibit multiorgan toxic side effects seen with long-term use of amiodarone

SOTALAR (sotalol) is available as 40 and 80 mg tablets and 10 mg/ml injections. SOTALAR tablets are indicated in life-threatening ventricular arrhythmias, non-sustained ventricular tachyarrhythmias, prophylaxis of supraventricular arrhythmias following cardiac surgery and for maintenance of sinus rhythm following conversion of atrial fibrillation or flutter. The initiation dose of SOTALAR tablets is 80 mg/day in single or two divided doses which can be increased at intervals of 2-3 days to 160-320 mg/day in two divided doses given at 12 hour intervals. SOTALAR injections are indicated in acute and life-threatening arrhythmias, programmed electrical stimulation in inducible ventricular and supraventricular arrhythmias and in those who are unable to take SOTALAR tablets. In acute arrhythmias, dosage for SOTALAR injections is 0.5-1.5 mg/kg. In programmed electrical stimulation, an initial bolus of 1.5 mg/kg of SOTALAR injection should be given, followed with maintenance infusion between 0.2-0.5 mg/kg/hour. For substitution in place of SOTALAR tablets, an infusion of SOTALAR injections between 0.2-0.5 mg/kg/hour should be used.

 

β blockers have been in clinical use for over 40 years and their usefulness for the management of cardiovascular diseases is well established. NEBICIP contains nebivolol, a novel, potent, third generation b blocker with the highest degree of b 1 selectivity amongst all currently available b blockers. Nebivolol also has a unique ability of stimulating nitric oxide (NO) production which causes vasodilation and improves endothelial function.

Nebivolol has demonstrated antihypertensive efficacy similar to that of other b blockers and other classes of antihypertensive drugs. Furthermore, nebivolol has been shown to significantly reduce the mortality and morbidity in elderly patients with chronic heart failure (CHF). In addition, nebivolol maintains or improves left ventricular function in patients with hypertension and also has anti-anginal efficacy.

NEBICIP is available in two strengths, NEBICIP 2.5 and NEBICIP 5 . It is indicated in hypertension and in elderly patients (age ≥ 70 years) with stable mild and moderate CHF. The recommended starting dose in hypertension is one tablet of NEBICIP 5 once daily, with or without food, which can be increased at 2-week intervals up to 40 mg. In severe renal impairment (CICr < 30 ml/min) and moderate hepatic impairment, recommended initial dose is one tablet of NEBICIP 2.5 once daily; upward titration should be performed cautiously if needed. In CHF, the initial dose is half-tablet of NEBICIP 2.5 , to be increased to one tablet of NEBICIP 2.5 once daily, then to one tablet of NEBICIP 5 once daily and then to 10 mg once daily.

 

Since activation of renin angiotensin system (RAS) plays a key role in the progression of renal and cardiovascular diseases, inhibitors of RAS [angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)] are now first-line treatments for progressive renal disease and hypertensive target organ damage.

The primary rationale justifying the use of ACE inhibitor and ARB combination is to ensure a more specific and complete RAS blockade. Clinical studies have demonstrated that ACE inhibitors and ARBs have specific renoprotective effects independent of BP reduction which include reduced risk of ESRD, reduced proteinuria and increased serum albumin levels and improvement in survival.

Amongst ACE inhibitors, ramipril has an extensive body of evidence regarding its clinical efficacy and safety. Amongst ARBs, telmisartan is an extensively used ARB on account of its unique properties. Hence, telmisartan and ramipril represents promising combination for providing renoprotection in high-risk hypertensives viz., hypertensives with diabetic and non-diabetic chronic kidney disease and diabetic hypertensives.

 CRESAR-R is the fixed-dose combination of telmisartan and ramipril from Cipla available in two strengths, CRESAR-R 2.5 (telmisartan 40 mg plus ramipril 2.5 mg) and CRESAR-R 5 (telmisartan 40 mg plus ramipril 5 mg). The usual recommended dosage is one tablet of CRESAR-R 2.5 or CRESAR-R 5 . In severe renal impairment or haemodialysis, a lower starting dose of one tablet of CRESAR-R 2.5 once daily should be used which may be titrated upward to a maximum of one tablet of CRESAR R 5 once daily . In mild to moderate hepatic impairment, dosage should not exceed one tablet of CRESAR-R 2.5/5 once daily.

 

Any disturbance in the blood coagulation system can lead to thrombosis which can clinically manifest as deep vein thrombosis (DVT), pulmonary embolism, unstable angina and myocardial infarction (MI). In such conditions, it is therefore prudent to use an anticoagulant in order to prevent the thrombotic sequelae. Although warfarin is the best amongst oral anticoagulants, it has a slow anticoagulant effect and a narrow therapeutic range. Low molecular weight heparins (LMWHs) have a rapid anticoagulant effect as compared to warfarin and offer several advantages over unfractionated heparin.

Enoxaparin is a unique chemical entity amongst LMWHs and has an extensive body of evidence on clinical efficacy and safety. Enoxaparin offers several advantages over unfractionated heparin including greater risk reduction of clinical events with safety profile similar to heparin. Enoxaparin is the only low-molecular-weight heparin to be approved by the US FDA in 7 indications for the prophylaxis and treatment of thromboembolic disease.

Enclex (Enoxaparin) is available in pre-filled syringes in two strengths, Enclex 40 and Enclex 60. Enclex is indicated for the prophylaxis of complications of unstable angina and non-Q wave MI, in the treatment of acute ST elevation MI, prophylaxis of DVT and in the treatment of acute DVT.

 

Epidemiological data has revealed that every 1 out of 5 Indian has hypertension and it is therefore of utmost importance to manage hypertension. More than 2/3 rd hypertensive patients require two or more drugs from different classes to achieve the target BP goals and hence, the use of fixed dose combinations may be more convenient.

Amlopres-NB is a fixed dose combination of 5 mg amlodipine and 5 mg nebivolol. Amlopres-NB can offer several benefits viz. additive BP reduction with an improved left ventricular function, NO mediated improvement in endothelial function, added anti-atherosclerotic effects and an excellent safety profile permitting its use in various classes of hypertensive patients. The recommended dosage of Amlopres-NB is one tablet once daily. In elderly patients (age above 65 years) and in patients with renal impairment, the dosage of Amlopres-NB is half tablet once daily which can be increased to one tablet once daily, if adequate blood pressure reduction is not achieved.